Burkholderia mallei is the causative agent of melioidosis


Burkholderia mallei is a Gram-negative, bipolar, aerobic bacterium, a human and animal pathogen of genus Burkholderia causing glanders; the Latin name of this disease (malleus) gave its name to the species causing it. It is closely related to B. pseudomallei, and by multilocus sequence typing it is a subspecies of B. pseudomallei. B. mallei evolved from B. pseudomallei by selective reduction and deletions from the B. pseudomallei genome. Most organisms within the Burkholderiaceae live in soil; however, B. mallei does not. Because B. mallei is an obligate mammalian pathogen, it must infect a host mammal to live and to be transmitted from one host to another.

The genome of B. mallei was sequenced in the United States by The Institute of Genomic Research. The size of the genome is smaller than that of B. pseudomallei. The B. mallei sequence revealed a chromosome of 3.5 mega base pairs (Mb) and a 2.3 Mb "megaplasmid”. Many insertion sequences and phase-variable genes were also found. The genome for B. mallei is made up of two circular chromosomes. Chromosome 1 is where genes relating to metabolism, capsule formation, and lipopolysaccharide biosynthesis are located. B. mallei has a polysaccharide capsule which indicates its potential as a pathogen. Chromosome 2 is where most of the information regarding secretion systems and virulence-associated genes are located.

No standardised system exists for differentiating between B. mallei and B. pseudomallei. The methods that have been used to differentiate and identify one strain from the other include ribotyping, pulsed-field gel electrophoresis, multilocus enzyme electrophoresis, random amplified polymorphic DNA analysis, and multilocus sequence typing. Comparing the DNA of B. mallei and B. pseudomallei must be done at the 23S rDNA level, however, since no identifiable difference is found between the two species at the 16S rDNA level. B. mallei is responsible for causing glanders disease, which historically mostly affected animals, such as horses, mules, and donkeys, and rarely humans. Horses are considered the natural host for B. mallei infection and are highly susceptible to it.

B. mallei infects and gains access to the cell of its host through lysis of the entry vacuole. B. mallei has bacterial protein-dependent, actin-based motility once inside the cell. It is also able to initiate host cell fusion that results in multinucleated giant cells (MNGCs). The consequence of MNGCs has yet to be determined, but it may allow the bacteria to spread to different cells, evade responses by the infected host’s immune system, or allow the bacteria to remain in the host longer. B. mallei is able to survive inside host cells through its capabilities in disrupting the bacteria-killing functions of the cell. It leaves the vacuoles early, which allows for efficient replication of the bacteria inside the cell. Leaving the cell early also keeps the bacteria from being destroyed by lysosomal defensins and other pathogen-killing agents. MNGCs may help protect the bacteria from immune responses.

In the first days of B. mallei infection, neutrophils, macrophages, and T cells go to the spleen in great quantities. The early cellular response to B. mallei infection involves Gr-1+ (antigen) cells, and implies their importance to immunity against this bacterial infection. T cells (nitric oxide) are actually more involved in combating B. mallei in the later stages of its infection of a host. B. mallei has been eradicated in the United States and most Western countries, but still affects animals in Africa, Asia, the Middle East, Central America, and South America. Many Western countries were able to eliminate the disease through glanders control programs and laws requiring notification of cases of infection to health departments and the destruction of any animal affected with B. mallei.

B. mallei and B. pseudomallei have a history of being on a list of potential biological warfare agents. The Centers for Disease Control and Prevention classifies B. mallei as a category B critical biological agent. As a result, research regarding B. mallei may only be done in biosafety level 3 facilities in the US and internationally. Though it is so highly infective and a potential biological weapon, little research has been conducted on this bacterium. B. mallei and B. pseudomallei under the policy of Institutional Oversight of Life Sciences Dual Use Research of Concern would be subject to oversight to ensure the responsible investigation of these agents.

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