Manual of Standards for Diagnostic Tests and Vaccines

The complete genome sequence of Burkholderia mallei ATCC 23344 provides insight into this highly infectious bacterium's pathogenicity and evolutionary history. B. mallei, the etiologic agent of glanders, has come under renewed scientific investigation as a result of recent concerns about its past and potential future use as a biological weapon. Genome analysis identified a number of putative virulence factors whose function was supported by comparative genome hybridization and expression profiling of the bacterium in hamster liver in vivo. The genome contains numerous insertion sequence elements that have mediated extensive deletions and rearrangements of the genome relative to Burkholderia pseudomallei. The genome also contains a vast number (>12,000) of simple sequence repeats. Variation in simple sequence repeats in key genes can provide a mechanism for generating antigenic variation that may account for the mammalian host's inability to mount a durable adaptive immune response to a B. mallei infection.

https://www.pnas.org/content/pnas/101/39/14246.full.pdf

Structural flexibility in the Burkholderia mallei genome

: Burkholderia mallei is a host-adapted pathogen and a category B biothreat agent. Although the B. mallei VirAG two-component regulatory system is required for virulence in hamsters, the virulence genes it regulates are unknown. Here we show with expression profiling that overexpression of virAG resulted in transcriptional activation of approximately 60 genes, including some involved in capsule production, actin-based intracellular motility, and type VI secretion (T6S). The 15 genes encoding the major sugar component of the homopolymeric capsule were up-expressed > 2.5-fold, but capsule was still produced in the absence of virAG. Actin tail formation required virAG as well as bimB, bimC and bimE, three previously uncharacterized genes that were activated four- to 15-fold when VirAG was overproduced. Surprisingly, actin polymerization was found to be dispensable for virulence in hamsters. In contrast, genes encoding a T6S system were up-expressed as much as 30-fold and mutations in this T6S gene cluster resulted in strains that were avirulent in hamsters. SDS-PAGE and mass spectrometry demonstrated that BMAA0742 was secreted by the T6S system when virAG was overexpressed. Purified His-tagged BMAA0742 was recognized by glanders antiserum from a horse, a human and mice, indicating that this Hcp-family protein is produced in vivo during infection.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2958.2007.05734.x

Type VI secretion is a major virulence determinant in Burkholderia mallei

creasing frequency in persons returning to the United States from Vietnam. The present review was undertaken in an attempt to bring into perspective our knowledge of both glanders and melioidosis as it relates to the biology of the respective causative organisms. Glanders is a specific zoonosis, primarily of the equines, that has been known since ancient times. In fact, the modern terminology comes from the Greek melis and its Latin derivation

The Pseudomallei Group: A Review

Burkholderia pseudomallei and Burkholderia mallei are closely related gram-negative bacteria that can cause serious diseases in humans and animals. This review summarizes the current and rapidly expanding knowledge on the specific virulence factors employed by these pathogens and their roles in the pathogenesis of melioidosis and glanders. In particular, the contributions of recently identified virulence factors are described in the context of the intracellular lifestyle of these pathogens. Throughout this review, unique and shared virulence features of B. pseudomallei and B. mallei are discussed.

Molecular Insights into Burkholderia pseudomallei and Burkholderia mallei Pathogenesis

As a natural infection, glanders occurs only in horses, mules, and donkeys. Other animals occasionally become infected from contact with infected solipeds. The most susceptible of these occasionally infected species are ferrets, moles, field mice, cats, and dogs. Sheep, goats, hogs, rabbits, white, mice, and house mice are reported to be less susceptible, and cattle are iune (Hutyra and Marek, 1926). The guinea pig is considered to be the most susceptible laboratory animal. The virulence of various strains of Malleomyces mallei has been reported to vary widely (Bernstein and Carling, 1909; Dudgeon et al., 1918), but in the virulence tests recorded in the literature large doses were given, and evaluation of virulence was made solely on the severity of disease produced. The wild rats of southeastern Asia constitute a natural reservoir of melioidosis. The disease, chronic in the rat, is thought to be transmitted to other animals, and to man, by ingestion or inhalation of materials contaminated with rat exereta. Rabbits, dogs, and cats have been found infected naturally, and an occasional case of infection has been reported in other domestic animals. Guinea pigs, mice, and rabbits have been used in studies of the experimentally produced disease (Stanton and Fletcher, 1932). Guinea pigs were reported to be almost universally susceptible, dying of a fulminating infection within 24 hours after a massive inoculation and within 3 weeks after a smaller inoculation. Monkeys were more resistant, developing fatal infection only after ingestion of massive doses. Rabbits and guinea pigs were susceptible to inoculation by the intraperitoneal or subcutaneous routes and by ingestion and inhalation. Although the organisms were reported as highly virulent, the inoculum always contained thousands to millions of organisms (0.01 to 1 ml of a 48-hour broth cultureStanton and Fletcher, 1932). No reference to a more quantitative evaluation of virulence by MLD or LDr0 determinations was found in the literature. The present studies include a comparison of the virulence of the several strains and their infectivity by various portals of entry, and a comparison of the susceptibility of several common species of laboratory animals. The source and characteristics of the strains of Malleomyces studied are given in the first paper of this series (Miller et al., 1948). The pathological changes and pathogenesis

Studies on Certain Biological Characteristics of Malleomyces mallei and Malleomyces pseudomallei: II. Virulence and Infectivity for Animals.

Studies on Certain Biological Characteristics of Malleomyces mallei and Malleomyces pseudomallei: I. Morphology, Cultivation, Viability, and Isolation from Contaminated Specimens.

Immunologic Studies With Malleomyces mallei and Malleomyces pseudomallei. I. Serological Relationships between M. mallei and M. pseudomallei.

The agglutination and complement fixation tests for glanders were originally developed as an aid in the detection of chronically infected horses.1 It has been reported that serum of infected horses gave positive agglutination tests2 in 84*^) and positive complement fixation tests3*4 in 97*^ of the samples. Because of the scarcity of reports on human glanders in the past 30 years, there is very little serological data on human cases in the literature. The agglutination with serums of normal individuals

https://www.jstor.org/stable/pdfplus/30089685.pdf

Immunologic Studies with Malleomyces Mallei and Malleomyces Pseudomallei. II. Agglutination and Complement Fixation Tests in Man and Laboratory Animals

Leo Cravitz

Papers

Studies on Certain Biological Characteristics of Malleomyces mallei and Malleomyces pseudomallei: II. Virulence and Infectivity for Animals.

Studies on Certain Biological Characteristics of Malleomyces mallei and Malleomyces pseudomallei: I. Morphology, Cultivation, Viability, and Isolation from Contaminated Specimens.

Immunologic Studies With Malleomyces mallei and Malleomyces pseudomallei. I. Serological Relationships between M. mallei and M. pseudomallei.

Immunologic Studies with Malleomyces Mallei and Malleomyces Pseudomallei. II. Agglutination and Complement Fixation Tests in Man and Laboratory Animals