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BIOLOGICAL PEST CONTROL USING PATHOGENS

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Introduction

Nematodes

Viruses

Van Driesche & Bellows Account

Bacteria

Protozoa

Fungi

References

 

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Introduction

Extensive discussions of the use of pathogens in biological control in tropical climates was given by Federici (1995, 1999) and Weiser (1984). Insects are susceptible to a variety of diseases caused by pathogens, many of which are acute and fatal, and can be important short-term regulators of insect populations. Therefore, insect pathogens are the subject of a considerable research effort aimed at developing the most effective pathogens as biological control agents. There has been interest shown for more than 100 years in controlling insects with pathogens, but their further development is now greater than ever due to the continually increasing need to replace chemical insecticides.  However, as of 2001, there are an ever increasing number of scientific papers dealing with the development of resistance to the various organisms, not unlike that witnessed earlier with flurocarbon insecticides.

In modern agriculture the mass production of microbial insecticides was more common than that for parasitoids and predators. This is because the production of microbes is easier than rearing predators and parasitoids. The latter are stored, packed and transported with a great risk of loss and also the methods for the technology available for their application is underdeveloped. Microbes are easily stored, packed and the method of application is very similar to that of chemical pesticides. Also the evaluation of treatment effects is performed in a way similar to insecticides, except that the period between application and effective mortality is usually longer. Other key references are Burges (1981), Burges & Hussey (1971), DeBach (1964), Franz (1980), Huffaker & Messenger (1976), Kurstak (1982), Poinar & Thomas (1978) and Weiser (1966, 1972, 1977).

In the tropics, environmental conditions of high RH, extreme temperatures and intensive insolation together with alternating heavy rains are important factors. Year-round temperatures which remain in the range suitable for the feeding and activity of insects provide suitable conditions for ingestion of adequate doses of oral materials, such as bacteria. On the other hand, high temperatures reduce viability of such pathogenic forms as fungal conidia, viral polyhedral inclusions and protozoan spores. Thee conditions are critical not only during application but also during storage and transportation of the materials. Infectivity is dependent on different strains' response to temperature, the range of a material's activity. High temperatures accelerate the development of target insects and also that of infections, especially those caused by bacteria and viruses. In principle there is no difference in infectivity to different pathogens in the tropics and in mild climates, all pathogens isolated in mild regions can be used in the tropics and vice versa (Weiser 1984).

Changes in RH also effect the efficiency of application of microbial insecticides. During storage high RH causes germination of some spores and ultimately their destruction. Products must be well formulated to guarantee a minimum of RH in the bulk material. This is the main reason for the increased demand for local production, which tends to avoid damage in storage and transportation. Not only the high RH but also extremes between dry periods before the rains come in savanna regions. During this dry period most entomophilic nematodes die or are so much reduced in distribution that their spread must begin again during the rainy season. Heavy rains may wash down any residue on plants, necessitating reapplication.

Another factor causing heavy losses on viability is solar radiation. In the tropics more than anywhere else it is important to direct an essential part of a particular microbial application to the lower parts of plants and under the leaves. Used in combination with treatments early in the morning or late in the afternoon, this may preclude the need for repeated treatments.

History.--Interest in using pathogens to control insects dates back over 100 years. Steinhaus (1975), Bassi (1835), Auduoin (1837) and LeConte (1874) and Metchnikoff (1879) suggested that pathogens might prove effective agents for controlling crop pests. But none of the early suggestions led to the successful deployment of pathogens. Renewed interest in the 20th Century followed the successful use of other natural enemies such as predaceous beetles and parasitic Hymenoptera. Control of the cottony cushion scale by natural enemies in the United States led to the establishment of permanent research programs by governmental agencies in the U.S. and several other countries aimed at using natural enemies, including pathogens, as pest control agents (Paillot 1933, Steinhaus 1975). Two early successes emerged from these programs, the development of Bacillus popilliae Dutky as a control agent for the Japanese beetle, Popillia japonica Newman, in the U,.S. (White & Dutky 1942), and use of the nuclear polyhidrosis virus (NPV) of the European spruce sawfly, Gilpinia hercyniae (Hartig), as a classical biological control agent in Canada (Balch & Bird 1944).

Shortly after World War II, E. A. Steinhaus was hired by the University of California (Steinhaus 1963). Trained as a bacteriologist, Steinhaus was well aware of the success attained with B. popilliae and the G. hercyniae NPV, and he began an concentrated effort aimed at using insect pathogens, particularly bacteria and viruses as control agents. Although other researchers were influential in the development of insect pathology and microbial control (Cameron 1973), the modern era of these two closely related disciplines was due largely to the leadership of E. A. Steinhaus. He reemphasized the use of Bacillus thuringiensis Berliner as a biocontrol agent, and his studies and those of Hannay (1953) and Angus (1954) were important in the commercialization and its successful use as a microbial insecticide. Although earlier studying the NPV of the alfalfa caterpillar, Colias eurytheme Boisduval, Steinhaus focused attention on the potential of viruses as microbial insecticides. His studies of viral and bacterial diseases of insects, and other pioneering efforts in the field of insect pathology, invigorated studies of the fungi and protozoa as control agents, and were important to the development of the international fields of insect pathology and microbial control.

Although there is an extensive literature on insect pathogens and microbial control, only one pathogen, B. thuringiensis is in routine use in control in industrialized countries, where it has been variously successful. It has been noted by many specialists that this pathogen is the one in which current interest regarding further development and use is the highest. He considered that it is worthwhile to consider why this is so because such an assessment identifies some of the key features required for a pathogen to be successful as a biological control agent. To do this requires a few definitions regarding the different ways in which pathogens are used or considered for use in insect control programs, and of the performance expectations by which the potential of insect pathogens and their degree of success are evaluated.

The guiding principle is one of economics; the pathogens that will be developed and used are those that are the most cost-effective, either in the short or long term. Classical biological control is the most cost effective, but the best example in insects is the use of an NPV to control the European spruce sawfly in Canada. Pathogens may also be used in seasonal introductions. The protozoan Nosema locustae Canning has been used in this way to reduce grasshopper populations over a period of several weeks. The common strategy is to use pathogens as microbial insecticides, and because this strategy has proven quite successful with bacteria and viruses, it will probably see even greater future use. Depending on the target pest, applications may often be fewer than those required with a chemical insecticide because the pathogens are quite specific and typically do not kill predatory and parasitic insects. Also, the reproduction of the pathogen in the target insect, as is true of viruses, adds to the amount of the pathogen in the treated environment, and this can extend control and cost effectiveness. A single application can yield effective seasonal control when the pests have only one or a few generations.

Performance expectations are important to consider when using pathogens. A successful pathogen reduces the pest to below an economic or transmission threshold routinely and reliably at a cost that is economical in proportion to the value of the crop or impact of the disease. Under most circumstances pathogens are evaluated on the basis of how they compare with chemical insecticides, leading to a microbial control agent paradox. Being generally agreed that the two properties of many chemical insecticides that were originally considered to be their best attributes are a broad spectrum of activity and a significant residual activity. Such properties are often responsible for the destruction of natural enemy populations and the production of insecticide resistance. But most insect pathogens have a narrow spectrum of activity and relatively poor residual activity. Although such are now considered desirable properties, until recently they have discouraged interest by industry in the development of many potentially useful pathogens because of the relatively high costs of development and registration in comparison to the likely return on investment.

Therefore, when considering the economics of pesticide development, it is apparent why B. thuringiensis has been the most widely developed and used insect pathogen. It compares favorably with chemical insecticides in many crop and forest systems where lepidopterous insects are the key or major pests. It is relatively inexpensive, easy to produce and formulate for use and it acts rapidly. It has a rather narrow spectrum of activity and possesses a low residual activity. Nevertheless, the range of insects it controls continues to provide a market large enough to justify commercial development. As discussed in the section of medically important arthropods, this bacterium most likely has been responsible for halting development of many other biological control possibilities, even though the latter might offer longer range and more thorough success.

Microbial pathogens which are used in pest control stem from four major groups of insect pathogens: viruses, bacteria, fungi and nematodes. Although nematodes sometimes are considered as parasitoids, the fact that they include in their activity the action of symbiotic bacteria, distinguishes them as a special group. Presently protozoa are not utilized on a large scale in field applications, but they may be useful in some integrated control situations .

Viruses

Overview

Granuloses

Iridoviruses

Cytoplasmic polyhedrosis viruses

Entomopoxviruses

Occluded baculoviruses

Use of Viruses as Insect Control Agents

Overview

Many viruses affect insects which are potentially useful in biological control. They may be divided into about 10 different groups according to their localization and their appearance under the optical microscope. Most are very host specific. Their formation and reproduction is bound on the genetic substance of the nuclei (DNA viruses) and sometimes connected with RNA replication (cytoplasmic viruses). In all viruses the infection is also egg transmitted and in many cases direct feeding of infectious materials do not immediately result in apparent lethal infections (Weiser 1984). Inapparent infections may remain in a population and then may appear in the next generation if suitable stresses are applied. Among the stresses initiating outbreaks of latent infections are crowding, cold storage, and secondary infections with other pathogens.

Most common are the nuclear polyhedrosis viruses (NPV) which appear as visible refringent irregular proteinic inclusions in the nuclei of the fat body, the hypoderm and other tissues. The nuclei are hypertrophic, which finally burst and the cell is destroyed. The host dies after a short period of time, and remains hanging on the last pair of larval legs. Its interior autolyses into a grey liquid with masses of refringent polyhedra, which do not stain with Giemsa. The polyhedra contain many virus rods. In the gut of the newly infected host the virus enters host cells and undergoes new development. Several NPVs are produced as formulated microbial insecticides. Most widely used is ELCAR against Heliothis, VIRIN NS against the gypsy moth, and VIRIN KS against the cabbage worm. There is also NPV available for control of caterpillars of Trichoplusia ni, the tussock moth, of Spodoptera littoralis and several other pests. It is essential to apply the virus against early stage larvae. In many cases the virus is only collected from outbreak areas and stored at 4°C for the next season. One Trichoplusia ni caterpillar is sufficient to treat one acre of infested alfalfa.

In sawflies the polyhedrosis is localized in the nuclei of the midgut. Several NPV's were used for control of important pests such as Neodiprion , Gilpinia and Trichiocampus. In these cases material was produced on collected caterpillars, stored and applied during the next season.

Granuloses are another type of DNA virus with rodshaped virions, each closed in a proteinic capsule which is visible only in dark field. Among the broadly used viruses of this group are the granulosis of the fall webworm and codling moth.

Viral rods without a proteinic capsule are those of the baculovirus such as infects the rhinoceros beetle, Oryctes rhinoceros. This pest of coconut palms in southeast Asia and the Pacific, has an infection attacking mainly the midgut and causing heavy mortality. The virus is produced in rearing stations on collected grubs of the beetle and used for spraying the sprouts of palms, or late instar grubs are infected and eclosed adults released so that they carry the infection into habitats of the beetle via the feces. In many areas the infective level of the virus in the field is much reduced and a recolonization of the infection with infected grubs is relied upon.

Less commonly used in field applications are the cytoplasmic polyhedrosis viruses, which are common in the cytoplasm of midgut cells of many caterpillars. They are usually not used alone but in conjunction with other pathogens, such as microsporidia. A specific virus group are the pox viruses which are localized in the cytoplasm of fat body cells, with large oval polyhedra with cushion-shaped virus particles. They are not very infectious and are not tested as microbial pathogens. Some non occluded viruses are important factors in reduction of very specific pests, as is the densonucleosis virus of the greater wax moth. The latter is very infectious, but easily inactivated due to lack of a protective coating. The group of iridoviruses is a natural control factor of mosquitoes and blackflies, of grubs of some beetles (e.g., Sericesthis), craneflies and others.

Viruses may be produced locally by collecting infected individuals in the field and storing them with care to suppress bacterial growth. Dry material remains viable for at least one year. A second step is the controlled production on caterpillars collected in nature or reared from eggs and infected in rearing cages in the laboratory. A third sophisticated step is the mass production on artificial media. This type of rearing avoids the usual contamination with other pathogens such as cytoplasmic polyhedrosis, bacteria or protozoa (Weiser 1984).

Viruses are obligate intracellular parasites, and as such must be grown in living hosts. Insect viruses must be grown either in insects or in cultured insect cells, as there is no method known for growing viruses on artificial media. Most viruses that occur in insects belong to one of seven major taxonomic families, but generally they are divided into two broad non-taxonomic categories: occluded viruses and non-occluded viruses. Occluded viruses are occluded with a protein matrix after formation in infected cells, forming paracrystalline bodies that are referred to as either inclusion or occlusion bodies. Non-occluded viruses occur freely or occasionally form paracrystalline arrays of virions that are also called inclusion bodies. However, the latter have no occlusion body protein interspersed among the virions.

In pest control, the biological properties of the viruses are more relevant than the physical and biochemical properties. The most important biological properties for the four most common virus types are as follows:

Iridoviruses are non-occluded DNA viruses that replicate in the cytoplasm of a wide range of tissues in infected hosts, causing disease that is usually fatal. Virions can form paracrystalline arrays in infected tissues, imparting an iridescent aspect to infected hosts, from which the name of this virus group is derived. Over 30 types are known, and all have proven extremely difficult to transmit per os. Host range of each type is quite narrow based on natural occurrence in host field populations. Prevalence and mortality rates in natural populations of host insects is typically <1% (Kelly & Robertson 1973).

Cytoplasmic polyhedrosis viruses are occluded RNA viruses which replicate and form large (ca. 0.5-2 milimicrons) polyhedral to spherical occlusion bodies in the cytoplasm of midgut epithelial cells causing a chronic disease. Infection in early instars retards growth and development, extending the larval phase by several weeks, which in many cases is fatal. This is a relatively common type of virus found among lepidopterous insects, and dipterous insects of the suborder Nematocera (mosquitoes, blackflies, chironomids). Detailed studies on isolates shown them to be easy to transmit per os to the original host and other species of the same order, and therefore the host range of this virus type is probably the broadest among the insect viruses (Katagiri 1981).

Entomopoxviruses are occluded DNA viruses which replicate in the cytoplasm of a wide range of tissues in most hosts, causing an acute fatal disease. Occlusion bodies, depending on the isolate, vary from being ovoidal to spindle-shaped and generally occlude 100 or more virions. They are most common from coleopterous insects, from which there are over 20 isolates, but also known from Lepidoptera, Diptera and Orthoptera. This virus type is easily transmitted per os, though the experimental host range of individual isolates seems relatively narrow, generally being restricted to closely related species (Granados 1981, Arif 1984).

Occluded baculoviruses consist of two types: the granulosis viruses (GVs) and the nuclear polyhidrosis viruses (NPVs). Both types are highly infectious per os, and in some insects these viruses cause widespread epizootics that can result in significant declines of larval populations.

The NPVs occur in a wide range of insect orders as well as from Crustacea, but they are most common in Lepidoptera (>1,000 isolates). Many occur as distinct viral species. NPVs are easily transmitted per os and replicate in the nuclei of cells, generally causing an acute fatal disease. The occlusion bodies are referred to as polyhedra because of their typical shape. They are large (ca. 0.5-2 milimicrons), and form in the nuclei, where each occludes as many as several hundred virions. The NPVs of Lepidoptera infect a range of host tissues, but those of other orders are typically restricted to the midgut epithelium. Some NPVs have a narrow host range, and may only replicate efficiently in a single species, while others such as the AcNPV, e.g., of the alfalfa looper, Autographa californica (Speyer), have a relatively broad host range and are capable of infecting species from different genera (Granados & Federici 1986, Blissard & Rohrmann 1990).

The GVs (ca. 200 isolates) are closely related to the NPVs but differ from the latter in several important ways. GVs are only known from Lepidoptera. Like NPVs, they initially replicate in cell nuclei, but replication involves early lysis of the nucleus, which in the NPVs only occurs after most polyhedra have formed. After lyses, GV replication continues throughout the cell, which consists of a mixture of cytoplasm and nucleoplasm. When completely assembled, the virions are occluded individually in small (200 x 600 milimicron) occlusion bodies called granules. Many GVs primarily infect the fat body, while others have a broader tissue tropism and replicate throughout the epidermis, tracheal matrix and fat body. One GV of the grapeleaf skeletonizer, Harrisina brillians Barnes & McDunnough, only replicates in the midgut epithelium (Federici & Stern 1990, Tweeten et al. 1981).

Use of Viruses as Insect Control Agents

The best example of the use of a virus as an insect control agent is the NPV of the European spruce sawfly, G. hercyniae, as a classical biological control (Balch & Bird 1944, Cunningham & Entwistle 1981). The European spruce sawfly was introduced into eastern Canada from northern Europe around the turn of the century and was a severe forest pest by the 1930's. Hymenopterous parasitoids were introduced from Europe in the mid-1930's as part of a biological control effort, and carried the NPV, which was first detected in 1936. Natural epizootics caused by the virus began in 1938, by which time the sawfly had spread to >31,000 km2. Sawfly populations were reduced to below economic thresholds by 1943. More than 90% of the control is attributed to the NPV.

Although viruses, particularly NPVs, are often associated with rapid declines in the populations of important lepidopterous and hymenopterous pests, the G. hercyniae NPV is the only true example of a virus that has proven effective as a classical biological control agent. Another baculovirus, the non-occluded baculovirus of the palm rhinoceros beetle, Oryctes rhinoceros (L.) has been a partial biological control success as introduced into populations it can yield control for several years, but usually dissipates and must be reapplied against the pest population (Bedford 1981). Thus, the control potential of most viruses is best evaluated by assessing their utility as microbial insecticides. From this position, the iridoviruses are essentially useless because of their poor infectivity per os. Cytoplasmic polyhidrosis viruses are not appreciably better because, although highly infectious per os, the disease they cause is chronic (Aruga & Tanada 1971, Payne 1981). CPVs have, nevertheless, been used in some situations, such as against the pine caterpillar, Dendrolimus spectabilis in Japan (Katagiri 1981). Entomopoxviruses have not yet been developed as control agents for any insect (Arif 1984, Granados 1981).

NPV's as Conventional Microbial Insecticides.--Because NPVs are common in and easily isolated from pest populations, production in their hosts is relatively inexpensive, and the technology for formulation and application is simple and adaptable to standard pesticide application methods. Most NPVs, however, are narrow in their host range, infecting only a few closely related species. Several can be grown in vitro in small volumes, but no fermentation technology exists for their mass production commercially. Despite such drawbacks, several NPVs have been registered as microbial insecticides, though few are marketed. There is a renewed interest in developing NPVs as insecticides due to the adverse effects of chemical insecticides and their increasing costs and because recombinant DNA technology offers potential for improving the efficacy of these viruses.

Production and Formulation.--Viruses are mass produced in larval hosts grown on artificial diets or natural host plants. Larvae are infected per os at an advanced stage of development, and reared either in groups or individually for species which are cannibalistic. After virus ingestion, the occlusion bodies dissolve in the alkaline midgut, releasing virions. In Lepidoptera, the virus first invades midgut epithelial cells where during the firs 24 hrs of infection it undergoes an initial colonizing phase of replication in the nuclei of these cells. No occlusion bodies are produced in these nuclei, but rather the progeny virions migrate through the basement membrane, and invade and colonize almost all other tissues. In these a cycle of replication occurs during which the virions are occluded in polyhedra. Maximum production of polyhedra occurs in tissues which are the most nutrient rich and metabolically active such as the fat body, epidermis and tracheal matrix. This definitive phase of viral disease occurs over a period of 5-10 days, and represents several cycles of replication as the virus spreads throughout the tissues and invades most host cells. The actual length of the disease depends on several factors including the host and viral species, larval instar at the time of infection, amount of inoculum and temperature. Near the end of the disease, after most polyhedra have formed, the nuclei lyse. As more nuclei lyse, the larva eventually dies after which the body liquifies, releasing billions of polyhedra. In commercial production larvae may be harvested prior to liquefication to keep bacteria, which quickly colonize dead larvae, at a lower level in the final product. Antibiotics also can be added to the diet to combat bacteria. After the larval production phase is complete, the larvae are collected and formulated. Formulation varies considerably, and depends on how the virus will be used (Ignoffo 1973, Shapiro 1986).

The production of lepidopteran GVs and sawfly NPVs is similar to that described lepidopteran NPVs (Cunningham & Entwistle 1981, Shapiro 1986). However, the sawfly NPVs differ from the lepidopteran NPVs in that the former only replicate and form polyhedra in midgut epithelial cells. Polyhedral yields are thus lower than those obtained with lepidopteran NPVs.

NPV's and Economics / Efficacy.--The extent to which conventional NPVs can be used as microbial insecticides depends on several factors which include the relative importance of the target pest in the pest complex attacking a crop, the amount of virus that must be used to control the pest in both the short term and long term, the value of the crop, and the cost and availability of alternative control measures. NPVs are suited for use where a single lepidopteran species is the major pest for most of the growing season on a crop with a high cash value where other available pest controls are not cost effective. Examples are NPVs that are effective against insecticide-resistant species of Heliothis and Spodoptera on crops such as corn, sorghum and cotton, and more importantly on tomatoes, strawberries and floriculture. The cost-effectiveness of these viruses is determined by the amount of virus that must be applied and the frequency of application necessary to maintain the pest below the economic threshold. This will, of course, vary with the kinds of virus, pest, crop and in different parts of the world. The mount of virus required is assessed in terms of larval equivalents (LEs) necessary to achieve effective control (Ignoffo 1973). The number of LEs required to obtain effective control is a critical component in the determination of cost-effectiveness. This can range from 150 LEs per ha. per treatment using H. zea NPV to control Heliothis on cotton to 500 LEs for the S. exigua NPV on lettuce and chrysanthemums. Also, the number of LEs required to control a specific pest can vary with the crop due to differences in plant phenology and chemistry. For example, whereas 500 LEs/ha. may be required to control S. exigua on lettuce, the value may be as high as 1,000 LEs on alfalfa or as low as 100 LEs on strawberries. This kind of economic evaluation is essential for determining whether a specific NPV merits commercial development as well as use against a specific insect on a crop. Additional examples may be found in Fuxa (1990), Shapiro (1986, 1992), Payne (1982, 1988) and Pinnock (1975).

Limitations.--viruses are not extensively used in industrialized countries because chemical pesticides are readily available and effective, although this may change with increasing residue and resistance problems. Nevertheless, viruses in comparison to chemicals are relatively slow to kill, possess a narrow host spectrum of activity, have little residual activity and lack suitable cost-effective in vitro production. But these limitations have not inhibited the development and use of viruses in some developing countries where NPVs and even a few GVs are used, especially on field and vegetable crops. Included are India, China and Latin America, Africa and southeast Asia (McKinley et al. 1989, Moscardi 1989, 1990). Reasons are that chemicals are too expensive, their widespread and heavy use has resulted in resistance, labor costs for virus production in vivo are low, production technology is simple, and registration for their deployment is not required or is easily secured.

Improvement of NPVs with Recombinant DNA.--Because conventional viral insecticides are relatively slow in killing and have a narrow host range, it is possible that both of these limitations may be overcome through the use of recombinant DNA technology (Miller 1988, Maeda 1989, Hawtin & Possee 1992). One approach to improving the efficacy of viruses is aimed at developing broad spectrum viruses that will cause a cessation of larval feeding within 24-48 hrs of infection. This is done by engineering the viruses to express proteins such as enzymes or peptide hormones that disrupt larval metabolism, or peptide neurotoxins that paralyze or kill the insect directly. Because it already has a broader host range than most occluded baculoviruses, the AcNPV virus has been the subject of most of the engineering studies to 1995. The virus is engineered by placing the candidate gene under the control of a strong and late viral promoter. With this strategy, genes for juvenile hormone esterase (Hammock et al. 1990), B. thuringiensis endotoxins (Martens et al. 1990, Merryweather et al. 1990, Pang et al. 1992) and insecticidal neurotoxins from the straw itch mite, Pyemotes tritici, and the scorpions, Androctonus australis Hector, and Buthus epeus, have been engineered into the ACMNPV (McCutchen et al. 1991, Tomalski & Miller 1991). Of these the most promising has been the AcNPV expressing the P. tritici toxin, which shortened the time between infection and paralysis or death to less than 72 hrs in older larvae.

Engineering viruses to express insecticidal proteins in many cases should also result in an expanded host range, because in many lepidopteran host species that do not develop a disease when infected by conventional viruses, there can be limited viral replication. The less susceptible hosts develop a mild disease and survive infection. But, the same hosts infected by an engineered virus that expresses a potent insecticidal protein will probably die because the virus does not need to replicate very much in order to paralyze or kill the larva.

Bacteria

History of Bacillus thuringiensis

Modern Isolate Discoveries

Characteristics

Biological Properties

Bacillus popilliae for Scarab Control

Bacillus thuringiensis details

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Sporeforming bacteria are the most important in biological control due to the possession of resistant stages. Among these are Bacillus thuringiensis, Bacillus pppilliae and Bacillus sphaericus.

History of Bacillus thuringiensis.--A detailed history of B. thuringiensis given by Beegle & Yamamoto (1992) is paraphrased as follows:

The Bacillus thuringiensis Berliner story began in the first decade of the 20th Century when the Japanese bacteriologist S. Ishiwata isolated the bacillus from diseased Bombyx mori (L.) larvae. He named it Sottokin, which means "sudden death bacillus." He described the pathology it causes in silkworm larvae and its cultural characteristics (Ishiwata 1905a). He also noted that many of the larvae that did not die when exposed to the bacillus were very weak and stunted. In a subsequent report (Ishiwata 1905b) he stated that "From these experiments the intoxication seems to be caused by some toxine, not only because of the alimentation of bacillus, the death occurs before the multiplication of the bacillus..." This showed that from the very beginning it was realized that a toxin was involved in the pathogenicity of B. thuringiensis. Ernst Berliner (1911, 1915) isolated a similar organism from diseased granary populations of Anagasta kuehniella (Zeller) larvae from Thuringia, Germany, which he named Bacillus thuringiensis, and because Ishiwata did not formally describe the organism he found, Berliner is credited with naming it.

Aoki & Chigasaki (1916) reported on their studies of Ishiwata's isolate, noting that its activity was due to a toxin present in sporulated cultures, but not in young cultures of vegetative cells. The toxin was not an exotoxin because it was not found in culture filtrates. It is obvious from their data on inactivation of the toxin by acids, phenol, mercuric chloride, and heat that they had a protein. Nothing further was accomplished with B. thuringiensis for over a decade, which was due perhaps to the fact that in Japan the Sotto disease was not a serious problem in silkworm culture and in Europe World War I was in progress. Berliner's isolate was lost, but in 1927 Mattes reisolated the same organism from the same host as did Berliner (Heimpel & Angus 1960a). Mattes' isolate was widely distributed to laboratories in various parts of the world, and most of the early commercial B. thuringiensis-based products and most of the early microbial control attempts used this isolate (Norris 1970). Both Berliner and Mattes observed in addition to the spore, a second body, which they called a Restkörper in the developing sporangia.

A serious problem with the European corn borer, Ostrinia nubilalis (Hübner) in corn in North America led to the formation of the International Group for Corn Borer investigation. At a meeting in Chicago, IL. it was proposed to attempt to use B. thuringiensis as a control agent (Briggs 1986). Under this program field trials were conducted in Hungary by Husz in the late 1920s and early 1930s, and Vouk and Metalnikov in Yugoslavia in the early 1930s. The results ranged from inconclusive to promising. The depressed economic conditions in the 1930s in North America resulted in an end to funding of the corn borer work (Heimpel & Angus 1960a, Weisner 1986). But because of the promising nature of some of the B. thuringiensis field trials, commercial production was begun in France by Laboratoire Libec, and the product Sporeine became available in 1938. World War II stopped further production. Jacobs (1951) reported on the effectiveness of Sporeine, finding that he could protect flour from A. kuehniella by applying Sporeine to the flour.

In the early 1950s Steinhaus at the University of California at Berkeley published several articles (Steinhaus 1951, 1956a, 1956b) that stimulated interest in the United States in the use and commercial exploitation of B. thuringiensis as a microbial control agent of some lepidopteran pest insects. In 1951 Steinhaus grew B. thuringiensis in large cafeteria trays containing nutrient agar, washed the spore-crystal complex off after sporulation, and used the recovered material in a successful field trial against Colias eurytheme Boisduval larvae on alfalfa (T. Angus 1988, pers. commun. to C. Beegle). Steinhaus knew a researcher with Cutter Laboratories in Berkeley, where antibiotics and vitamins were produced in aerated and agitated liquid media in relatively large fermenters. Cutter Laboratories then produced B. thuringiensis preparations for Steinhaus which he used successfully against C. eurytheme larvae (Briggs 1986). In 1956 Steinhaus and R. A. Fisher met with the president of Pacific Yeast Products, J. M. Sudarsky, to explore the practicality of producing a B. thuringiensis-based product (Heimpel 1972). Pacific Yeast Products (later Bioferm Corporation) was a yeast and vitamin B-12 producer in Wasco, CA. The decision was made to produce B. thuringiensis and by 1957 a product called Thuricide was available for testing. Thuricide was formulated as liquid concentrates, dusts, and wettable powders. Bioferm successfully petitioned the U. S. Food and Drug Administration for an exemption from residue tolerances of B. thuringiensis products on agricultural crops, on the presumption of safety toward beneficial insects, plants, humans and animals based on historical evidence (Briggs 1986). The Wasco facility in 1992 is owned by Sandoz, and is still producing a variety of B. thuringiensis products. In 1959 Nutrilite Products entered the market with their product Biotrol (Ignoffo 1973), which was produced by semisolid fermentation on a wheat bran medium. Several other U.S. Companies (Merck, Agritrol; Rohm & Haas, Bakthane; and Grain Producers, Parasporine) produced B. thuringiensis for short periods (van der Geest & van der Laan 1971).

Besides the production of Sporeine in France in the late 1930s, there was the development of B. thuringiensis production and usage in European socialist countries in the 1950s. The 058 strain of B. thuringiensis subsp. thuringiensis was used by the Research Institute of Antibiotics in Roztoky, Czechoslovakia, to produce the product Bathurin in 10,000-L fermenters. This material was priced at 40 korunas per kilogram and was used for control of insect pests on vegetables and ornamentals, and in forests and orchards (Weiser 1986). In the former Soviet Union, the All Union Institute for Microbial Products for Plant Protection produced the product Entobaktrin using a B. thuringiensis subsp. galleriae isolate found by Isakova in 1956 (Isakova 1958). In Moscow, the government agency for the Direction of Microbial Industry started producing the product Dendrobacillin for use against larvae of the Siberian silkworm, Dendrolimus sibiricus Tshetverikov, a serious pest of conifers. The B. thuringiensis subsp. dendrolimus isolate used in the product was discovered in 1954 by E. V. Talahaev from dead D. sibiricus larvae (Talalaev 1956). The same facility also produced the product Insektin using a B. thuringiensis subsp. thuringiensis isolate. Insektin also was used for forest protection (Weiser 1986). In Yugoslavia the product Baktukal was produced by Serum Zavod, in Germany Hoechst produced Biospor, and in France Procidia produced Plantibac.

Edward Steinhaus was perplexed that at sporulation in B. thuringiensis the spores were not centrally located, but they were rather displaced to one end. In 1953 Steinhaus sought the advice of the Canadian bacterial morphologist C. Hannay regarding this phenomenon (T. Angus, 1988 pers. commun. to C. Beegle). Upon examining B. thuringiensis sporulated cells, Hannay noticed a second body in the sporangium, as had Berliner and Mattes. But Hannay went one step further and speculated that the parasporal inclusion bodies had some role in the pathogenicity of the bacterium toward susceptible lepidopterous larvae (Hannay 1953). Coincidentally in 1951 Steinhaus published a picture of a sporulated and lysed B. thuringiensis culture showing bipyramidal crystals, but did not make note of them in the text. T. A. Angus, a Canadian also was working with B. thuringiensis at the time, and Hannay sent Angus a copy of his manuscript prior to publication. Angus quickly proved that Hannay was correct, that the parasporal crystal was responsible for the toxicity of B. thuringiensis (Angus 1954). Angus showed that spores by themselves had not effect, and that dialyzed supernatant of alkali-dissolved crystals had the same toxic action as did the spore-crystal complex when fed to B. mori larvae. Angus also noted that toxicity varied with crystal count, and was independent of the number of spores present.

Beegle & Yamamoto (1992) concluded that the early years were not without problems. For about the first 10 years of B. thuringiensis commercial production, the amount and range of usage was limited because of low potency strains (nearly all subsp. thuringiensis) and inadequate standardization techniques. The latter were a result of a decision by Pacific Yeast Products Co. to optimize spore production in their fermentations. This eventually led to the acceptance of spore counts by the Pesticide Regulation Division of the USDA-ARS as a method to standardize B. thuringiensis-based products (Heimpel 1972). This was disastrous because there proved to be no reliable relationship between spore counts and insect killing power (Angus 1954, Menn 1960, McEwen et al. 1960, Hall et al. 1961, Mechalas & Dunn 1964, Krieg 1965b, Burgerjon 1965, Vago & Burges 1964, Burges 1967, Dulmage & Rhodes 1971). It was also an unsettled period in regards to the identification and classification of B. thuringiensis.

Modern Isolate Discoveries.--According to Beegle & Yamamoto (1992), before 1970 the majority of B. thuringiensis products were based on subsp. thuringiensis, and often contained heat-tolerant Beta-exotoxin. These products were low in activity, having potencies from a few hundred to ca. 1000 IU per mg. These low potency products could not compete with chemical insecticides in either efficacy of cost because of expedient controls demanded by users at the time. Probable long-range effects on lowering Lepidoptera population vigor and densities as reported by Legner & Oatman (1962) & Oatman & Legner (1964) were not considered of sufficient expediency. The presence of Beta-exotoxin in some of the products resulted in the confusing host range and safety data that exist in the literature for those subsp. thuringiensis-based products. In 1962, Edouard Kurstak isolated another subspecies of B. thuringiensis from diseased A. kuehniella larvae from a flour mill at Bures sur Yvette near Paris, France (Kurstak 1962). He gave the isolates, designated K-17 and K-18 (short for AP.77.BX.17 and AP.77.BX.18), to A. M. Heimpel of the U. S. Dept. of Agriculture in 1962 and again in 1963 (Beegle & Yamamoto 1992). In 1970 Dulmage reported isolating from diseased Pectinophora gossypiella (Saunders) larvae an isolate he named HD-1 (Dulmage 1970). DeBarjac & Lemille (1970) examined the five isolates (AP.77.BX.17 and AP.77.BX.18 from Kurstak, K-17 and K-18 from Heimpel and HD-1 from Dulmage) and found that on the basis of flagellar serotyping they were a new subspecies of B. thuringiensis, which they named kurstaki.

One of the new subsp. kurstaki isolates (HD-1) was responsible for B. thuringiensis-based products being able to compete with chemical insecticides on the basis of efficacy and cost against insects such as Trichoplusia ni (Hübner) on cruciferous crops. The kurstaki isolate proved to be 20- to 200-fold more potent than the isolates in the existing commercial B. thuringiensis products (Dulmage 1970). In 1970 Abbott Laboratories entered the market with Dipel, which was the first commercial preparation based on the new kurstaki isolate. It was not long before all companies producing B. thuringiensis-based produced in the United States were subsp. kurstaki. By 1992 several million kilograms of kurstaki-based products were produced annually in the United States with usage registered for almost 30 crops and against over 90 pest insect species worldwide. The single largest market for B. thuringiensis-based products by 1992 was against forest insect pests in North America.

However, the market for kurstaki based products in agriculture fell to about 20% of its peak in the mid-1970s, due largely to competition from synthetic pyrethroids. In the late 1970s a considerable amount of kurstaki-based B. thuringiensis product was used on cotton for Heliothis spp. Because HD-1 was not the most active isolate against Heliothis available, a number of the most promising isolates were evaluated in the laboratory and field tested. Of the cultures in the Brownsville, TX. U.S. Dept. Agriculture B. thuringiensis collection (now at Peoria, IL>0, HD-263, a kurstaki subsp. originally isolated by G. Ayerst from a dead Ephestia cautella (Walker) pupa found by H. Burges in England, proved to be superior against all Heliothis spp. tested. Three years of field testing against H. virescens (F.) on cotton showed HD-263 to be superior to HD-1 (Beegle 1983). But, even at very high application rates, HD-263-based material did not control H. virescens larvae as well as the synthetic pyrethroid chemicals. Discovery of isolates with superior activity against H. virescens caused Adang et al. (1983) to clone the crylA(c) gene that codes for a crystal protein that is highly toxic to Heliothis spp. (Hofte & Whiteley 1989). In the mid-1980s Ecogen Corporation tried to develop a B. thuringiensis product using genetically manipulated isolates containing the crylA(c) gene. Although Ecogen created HD-263-derived isolates much more potent than the original isolate, the higher laboratory potency was never translated into similar field performance (I. Gard 1987, pers. comm. to C. Beegle). Eventually Ecogen abandoned this project. The question of why B. thuringiensis-based products are not effective against Heliothis spp. on cotton is unclear especially as there are formulations which are certainly potent enough to Heliothis spp., especially H. virescens. Beegle & Yamamoto (1992) believed the reason is that Heliothis during most of its larval life on cotton is a covert feeder, spending most of its time inside the squares and bolls. Because B. thuringiensis has to be ingested to be effective, all the potency is not going to do any good if the target pest insect does not consume the applied material. During the period that Abbott Laboratories was attempting to penetrate the cotton insect pest control market with Dipel, nearly 100 adjuvants were examined in hopes of finding one that would result in B. thuringiensis being adequately effective against Heliothis spp. on cotton (T. Couch, 1985, pers. comm. C. Beegle). Beegle & Yamamoto (1992) thought it might take the development of a highly effective bait for use with B. thuringiensis crystal toxin gene(s) and expressing high levels of crystal toxin (Perlak et al. 1990), for b. thuringiensis to be adequately effective against Heliothis spp. on cotton.

Another commercial used kurstaki isolate, NRD-12, was discovered by Normand Dubois of the U.S. Dept. of Agriculture Forest Service (Dubois 1985). It was significantly more active against Spodoptera exigua (Hübner) larvae than HD-1. But, Moar and associates presented evidence that this was true only when the HD-1 isolate being compared with NRD-12 is missing the crylA(b) crystal toxin gene which codes for a toxin that is especially active against S. exigua larvae (Moar et al. 1989, 1990). NRD-12 is a unique kurstaki isolate because it produces considerable levels of heat-tolerant exotoxin under conditions favorable for production of such exotoxin. The other subsp. kurstaki isolate that is known to produce measurable amounts of heat tolerant exotoxin is 62B-1-(4) discovered by Michio Ohba in Japan (Ohba et al. 1981). In the mid-1980s Sandoz registered the product Javelin, based on NRD-12, with the U.S. Environmental Protection Agency. In late 1985 Sandoz replaced NRD-12 with another subsp. kurstaki isolate which did not produce detectable levels of heat-tolerant exotoxin, but was as active as NRD-12 against S. exigua larvae, for use in the product Javelin Current subsp. kurstaki-based commercial products listed by Beegle & Yamamoto (1992). The worldwide market for kurstaki-based products for forestry and agriculture was estimated at $20-25 million in the U.S. in 1992 (Beegle & Yamamoto 1992).

Goldberg & Margalit (1977) discovered B. thuringiensis isolates with mosquito larvicidal activity after screening ca. 1000 isolates from 10 soil samples taken from known mosquito larval breeding sites in Israel. Only 1% of the isolates showed mosquito larvicidal activity, but one (ONR60A) had extremely high activity. The new isolate was classified as B. thuringiensis subsp. israelensis (de Barjac 1978), and had a good level of activity and killing speed. Mortality of Aedes aegypti (L.) larvae could occur as soon as 30 min. after exposure (Singer 1980) and with an LC-50 as low as 22 ppb (Dame et al. 1981). Goldberg obtained a U.S. patent on the organism and assigned the patent to the U.S. government (Goldberg 1979). By 1992 both U.S. and European companies were producing and marketing subsp. israelensis-based products for use against mosquito and blackfly larvae. The worldwide market for israelensis-based products was ca. $10-US million.

Keio Aizawa of Kyushu University in Japan discovered an isolate in 1962 that Bonnefoi & de Barjac (1963) determined as a new subspecies, naming it aizawai. Subsp. aizawai isolates were particularly effective against Galleria mellonella (L.) and Spodoptera spp. larvae. However, no B. thuringiensis isolate is nearly as active against Spodoptera spp. larvae as are the best isolates against the larvae of such species at T. ni and H. virescens. When beekeepers lost the use of certain effective insecticides for killing G. mellonella larvae in honey combs, Sandoz recognized that empty niche and developed their product Certan, based on an aizawai isolate, for control of G. mellonella larvae in honey comb. The market was small at ca. $50,000 U.S. per year.

By 1992 the latest new B. thuringiensis subspecies to be found that had commercial promise was tenebrionis, which was found by Krieg and associates in diseased Tenebrio molitor L. (Krieg et al. 1983), and is active against other Coleoptera. Herrnstadt et al. 91986) of Mycogen Corp reported finding a B. thuringiensis isolate active against coleopterous larvae, naming it B. thuringiensis subsp. san diego. Krieg et al. (1987) compared the two isolates, tenebrionis and san diego, and found them to be identical in terms of biochemistry; serology; antibiotic and chemotherapeutic inhibition; plasmid DNA; crystal morphology, solubility, and protein pattern; and host range. As the two isolates appeared identical, and tenebrionis was described first, it follows that tenebrionis is the correct name for the subspecies and the name "san diego" should only be used to designate the particular isolate of subsp. tenebrionis that Mycogen utilized. In 1988 Mycogen brought out its product M-One based on its isolate, primarily for use against larvae of Leptinotarsa decemlineata (Say) on potatoes. M-One was reported effective against small L. decemlineata larvae in warm weather, but was less effective in cool weather or against large larvae (Ferro & Lyon 1991; Zehnder & Gelernter 1989). Because of the problem of resistance to chemical insecticides by L. decemlineata in some potato growing areas, subsp. tenebrionis-based products have become the preferred L. decemlineata control product. In those areas it was noticed that a reduction in the level of resistance to synthetic pyrethroids in L. decemlineata occurred. This accidental discovery suggested the possibility of managing resistance to both control agents by alternating usage of each (D. Ferro, 1992, pers. commun. C. Beegle). Ecogen received registration for its product Foil in 1992, which was a combination f subsp. kurstaki and subsp. tenebrionis for use against both lepidopterous and coleopterous pests on potatoes. Beegle & Yamamoto (1992) listed a number of subsp. tenebrionis-based products).

Characteristics.--Bacillus thuringiensis causes extended mortality in nature among lepidopterous insect epizootics or in mass culture. High mortalities appear in dense populations of stored product pests, such as Ephestia kühniella, Plodia interpunctella and others, in the rearing of silkworms and in laboratory mass rearings of insects in general. The rather thick, clear staining rod of this bacillus produces a diamond-shaped refringent crystal of proteinic material in addition to the spore itself, which is the seat of its activity. The crystal dissolves in the midgut of Lepidopteran caterpillars to a toxin which attacks the membranes of midgut cells and finally kills the host. In other hosts the Lep-toxin does not find proper conditions for its activation and is harmless. Therefore, it is safe for all organisms including humans and other vertebrates. Conditions in different caterpillars differ slightly, and there are of the >1,000 known isolates, groups of strains which have some specific affinity to specific hosts. With flagellar antigens the strains are divided into more than 20 serotypes differing also in some principal details such as their activity against noctuids and large caterpillars, activity against the wax moth, etc. Strains are selected for mass production for controlling caterpillars of agricultural pests. Serological grouping does not dictate the general virulence of a strain and it can be isolated with minimum or maximum virulences. Improvement of the virulence is achieved by selection, optimum medium for cultivation and passing over selected host insects. With increased virulence the time between administration and mortality is reduced, from a usual five days to three or less.

Bacillus thuringiensis is produced in large fermentors, dried, blended with inert ingredients, emulgators and stickers. It must be stored in the dry state. Ready mixtures have to be used during the same day. It is administered as a food and for maximum effect must be ingested in adequate quantity. Applications on the first three instars of a caterpillar are preferable. Spores on leaves are damaged by ultraviolet light and usually retain their activity for <1-week. Spraying from below and to the sides of plants is recommended. Biological activity of a preparation is determined on the basis of comparison with a standard of Heliothis or Lymantria. Local target insects can also be used for comparison with a standard. The activity is expressed in bio-units (Weiser 1984).

Some serotypes are able to produce a soluble exotoxin. This is released into the liquid fermentation medium and may be removed by centrifugation. However, it remains in the total spray-dried formulations because it is a thermostable toxin. This toxin interferes with DNA-dependent RNA polymerase and it is a general rather than nonspecific poison. Its active dose for insects has a safe range far below vertebrate activity, but it is not yet used broadly in pest control. In the Soviet Union this kind of material is used for the control of housefly maggots and the Colorado potato beetle and other pests. In low doses treated animals develop teratologies in their moth parts and legs.

Bacillus thuringiensis preparations are used for the control of most lepidopteran pests of agriculture (Legner & Oatman (1962) & Oatman & Legner (1964)). Due to their nontoxicity to the honeybee, they can be used on flowering plants. The usual dosage is 0.5-1.5 kg/ha of the preparation, according to density of the treated crop. Material is used in a water suspension. Lepidoptera are divided into three major groups of susceptibility. Most susceptible are Pieris, Plutella, Tortricidae, bagworms and moths. Here the dosage is 0.2-0.5 kg/ha. The second group contains most caterpillars, mainly the Noctuidae, armyworms, budworms, large caterpillars, etc., where the dosage is 1-1.5 kg/ha. In the third group there are hidden caterpillars (e.g., codling moth) that do not normally access treated leaves, or exceptionally resistant species such as Spodoptera.

Bacillus thuringiensis may be used in a mixture with insecticides. Generally the bacillus is introduced to a diluted insecticide to avoid damage to from solvents. Mixtures are not recommended because they usually are made with reduced content of insecticide and after expiration of the microbial agent the sublethal insecticide may produce resistance. There is no resistance to B. thuringiensis beyond normal fluctuation of activity after 30 generations of genetic stress and pressure (Weiser 1984). The strain used most in agriculture is H-3 kurstaki. For specific treatment of the wax moths the serotype H-7 aizawai was developed. Of economically important nontarget insects the silkworm is the only endangered species and where sericulture is developed proper care must be taken to avoid its introduction into the cultures. This danger is analogous to that from insecticides. There is good adaptation of B. thuringiensis preparations to entomophagous insects. The five day phase before full mortality enables parasitoids to finish their development and active adult parasitoids are not encumbered. The shelf life of dry formulated powders is >2 years, the spores and crystal toxin remain active for more than 15 years. Moisture usually causes spore germination and decreases the activity of the preparation.

Among the many isolates there are some strains with activity for beetles, but their development as microbial insecticides has not been accomplished.

The serotype H-14 (B. thuringiensis israelensis) is a very important strain which infects and kills mosquito and blackfly larvae. All tests have shown identical parameters of this strain with other strains. Only the endotoxin is entirely different, being nontoxic for Lepidoptera and highly toxic to mosquitoes. The crystal is more spherical and ultrastructurally is composed of two different substances. The larvae respond after feeding for three hours with a symptom of knock down, hanging motionless on the surface. Once this symptom appears there is no recovery for the larvae and they die in 24-48 hrs. The active concentration of the bacteria ranges from 500-1,000 cells/ml. Due to the ecological range of distribution of mosquito larvae in shallow water, the volume factor does not need to be calculated and a dosage of 1 kg/ha of wettable powder for treatment of mosquito habitats is usual. The difference in feeding of early and late instar larvae is not very important and therefore treatments are timed for the period of older larvae, before pupation. The treatment does not hold longer than one week and must be repeated when last instar larvae are again present. Bacteria are filtered away by different aquatic organisms (e.g., rotifers, ciliates, crustaceans, etc.). If large dosages are used, some chironomid midges are damaged. For the treatment of running water that contain larvae of blackflies, it is necessary to provide a concentration of 1.5 mg/l of Tecnar or Vectobac for 10 min., by continuous release of the concentrate.

Other bacteria are less commonly used in field application. Bacillus sphaericus is specific only for mosquitoes. Bacillus popilliae was used earlier for control of such grubs as Popillia japonica in the United States. The bacterium has a large parasporal body and infects grubs by feeding but only very slowly. It was mass produced by injection of pasteurized spores into normal field collected grubs. Dying or dead infected grubs were triturated with talcum or bentonite and the mixture was dusted over lawns infected with grubs. Several local strains occur in populations of different grubs in Australia and New Zealand and Weiser (1984) believed they must be present also in other areas.

Bacteria are relatively simple unicellular microorganisms lacking internal organelles such as a nucleus and mitochondria, and reproduce by binary fission. With few exceptions most bacterial used as microbial insecticides grow readily on a wide variety of inexpensive substrates, a characteristic which facilitates their production. Most bacterial currently in use or under development as microbial control agents for insects are spore-forming members of the bacterial family Bacillaceae, in the genus Bacillus. Such pathogenic bacilli occur in healthy and diseased insects, but they also occur and can be isolated from many other habitats including granaries, plants, frass, soil and aquatic environments.

Biological Properties.--Two major types of bacteria used in insect control are those which cause fatal infectious diseases and those which kill insects primarily through the action of insecticidal toxins. Bacillus popilliae Dutky is an example of the firs type. It is a bacterium that infects and kills Coleoptera larvae, particularly soil-inhabiting Scarabaeidae. The second type is Bacillus thuringiensis Berliner, a species which produces toxins, both protein endotoxins and nucleotide exotoxins, that are able to kill insects whether or not they are directly associated with the bacterium. Biologists have made extensive use of the latter property by inserting the genes encoding various endotoxins into other microorganisms and plants thereby making them insecticidal (Fischoff et al. 1987, Vaeck et al. 1987. Perlak et al. 1990, Raymond et al. 1990).

Bacillus popilliae for Scarab Control

Scarab milky disease was first discovered over 50 years ago (Dutky 1937, 1963). It is caused by B. popilliae and B. lentimorbus. The term "milky" derives from the opaque white color characterizing diseased larvae which results from the accumulation of sporulating bacteria in the hemolymph. The disease in initiated when grubs feeding on the roots of grasses or other plants ingest the spores, the latter than germinating in the midgut and vegetative cells. They invade the midgut epithelium where they grow and reproduce, changing in form as they progress toward invasion of the hemocoel (Splittstoesser et al. 1978). After passing through the basement membrane of the midgut, the bacteria colonize the hemolymph over a period of several weeks and sporulate reaching populations of 108 cells per ml. The disease is fatal if the larvae ingest a sufficient numbers of spores early in development, and dead larvae become foci for spores which can serve as a source for infection for over 30 years (Klein 1981).

One drawback of B. popilliae and its close relatives is that suitable media for their growth and mass production in vitro are not available. This has encumbered both research and large scale commercial development of B. popilliae. Commercial development is from field-collected scarab larvae. Such larvae are collected from field populations, injected with spores, and held in environmental chambers for 1-2 weeks until the bacteria have sporulated and killed most of the larvae. Powdered formulations of the bacterial spores are then made by drying and grinding larvae. Such preparations may be applied to soils infested with grubs at rates of ca. 1 kg. of formulation per ha. Although treatment can be expensive, a single treatment typically lasts for 10 years.

Bacillus thuringiensis

This bacterium has been the most widely used insect pathogen to date. A complex of bacterial subspecies comprises this bacterium, all of which are typified by the production of a parasporal body during sporulation. This parasporal body contains one or more proteins, often in crystalline form, many of which are highly toxic to certain insects. In the insecticidal isolates, the toxins are known as endotoxins and often occur in the parasporal body as protoxins which after ingestion are activated by proteolysis in the gut. The activated toxins destroy midgut epithelial cells, causing death.

Systematics & Biology.--B. thuringiensis is very closely related to Bacillus cereus, which is separated by the occurrence of the parasporal body in the former (Baumann et al. 1984). It seeps that in almost all known isolates of B. thuringiensis, the proteins which make up the parasporal body are encoded on plasmids borne by the bacteria. These plasmids can be lost during growth and reproduction, which can change the description to B. cereus, using conventional identification and classification.

At least several thousand isolates of B. thuringiensis have been obtained from a variety of sources by 1991. These include soil, frass, grain dust, water, and living and dead insects. They are divided into groups, of which there are nearly 30 (De Barjac & Frachon 1990), that are differentiated on the basis of the H antigen, i.e., flagellar serotype, which is indicated by a number or a number and letter combination (e.g., H3a3b, etc.) as well as a serovar name (e.eg., H-1 thuringiensis, H3a3b kurstaki). A list of the H antigen types and serovar names as of 1990 is provided by Beegle & Yamamoto (1992). The H antigen and serovar are usually used to identify a specific isolate, although the serovar name is often referred to as either a subspecies or variety (e.g., B. thuringiensis subsp. thuringiensis, or B. thuringiensis var. thuringiensis).

Beegle & Yamamoto (1992) pointed out that B. thuringiensis began as an independent species distinguishable from other bacilli, such as B. cereus Frankland & Frankland. It is close to B. cereus except that it produces a crystal at sporulation (sometimes more than one), which is usually bipyramidal in shape (sometimes square, flat or amorphous), and is toxic to lepidopterous, dipterous or coleopterous insect larvae. This resulted in some taxonomic problems, and some bacterial taxonomists felt that B. thuringiensis should be a subspecies of B. cereus (Smith et al. 1952, Bordon et al. 1973). This is based on such observations as certain strains of B. thuringiensis and B. cereus both killed mice when injected intraperitoneally (Lamanna & Jones 1963); the spores of both shared common antigens (Yoder & Nelson 1960; Lamanna & Jones 1961) and showed cross sensitivity to bacteriophages (Yoder & Nelson 1960); it was not possible to separate B. cereus and B. thuringiensis by crossed immunoelectrophoresis of ultrasonic extracts of sporefree-grown vegetative cells