Burkholderia mallei

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Burkholderia mallei
Scientific classification Edit this classification
Domain: Bacteria
Phylum: Pseudomonadota
Class: Betaproteobacteria
Order: Burkholderiales
Family: Burkholderiaceae
Genus: Burkholderia
Species:
B. mallei
Binomial name
Burkholderia mallei
(Zopf 1885)
Yabuuchi et al. 1993
Synonyms

Bacillus mallei Zopf 1885
Actinobacillus mallei (Zopf 1885) Brumpt 1910
Pfeifferella mallei (Zopf 1885) Buchanan 1918
Malleomyces mallei (Zopf 1885) Pribram 1933
Loefferella mallei (Zopf 1885) Holden 1935
Acinetobacter mallei (Zopf 1885) Steel and Cowan 1964
Pseudomonas mallei (Zopf 1885) Redfearn et al. 1966

Burkholderia mallei is a

Gram-negative, bipolar[clarification needed], 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.[1] B. mallei evolved from B. pseudomallei by selective reduction and deletions from the B. pseudomallei genome.[2] Unlike B. pseudomallei and other genus members, B. mallei is nonmotile; its shape is coccobacillary
measuring some 1.5–3.0 μm in length and 0.5–1.0 μm in diameter with rounded ends.

Discovery and early history

Wilhelm Schütz and Friedrich Löffler first isolated B. mallei in 1882.[3] It was isolated from an infected liver and spleen of a horse.[4] This bacterium is also one of the first to be identified containing a type VI secretion system which is important for its pathogenicity.[5] In 1885, the German Botanist and Bacteriologist, Wilhelm Zopf (1846–1909) gave the pathogen its binomial name, after analyzing samples of the bacterium. He further refined his observations with the pathogen in 1886.[6]

Family Burkholderiaceae

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.[7]

Genus Burkholderia

B. mallei is very closely related to B. pseudomallei, being 99% identical in conserved

intracellular lifestyle.[8]

Genome

The genome of B. mallei was sequenced in the United States by

insertion sequences and phase-variable genes were also found.[3] 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.[4] Multilocus sequence typing has revealed that B. mallei most likely evolved from a B. pseudomallei clone reduction. About 1000 B. pseudomellei genes are absent or varying in the B. mallei genome. B. mallei's genome also has a large amount of insertion sequences.[8]

Taxonomy

Burkholderia mallei was first called "Bacillus mallei" and was in the genus Pseudomonas until the early 1990s. It is now part of the genus Burkholderia.[3]

Typing

No standardised system exists for differentiating between B. mallei and B. pseudomallei. The methods that have been used to differentiate and identify one

pulsed-field gel electrophoresis, multilocus enzyme electrophoresis, random amplified polymorphic DNA analysis, and multilocus sequence typing.[3] 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.[9]

Growth in culture

Both B. mallei and B. pseudomallei can be

microbiologists are unfamiliar with B. mallei and as a result it has frequently been misidentified as a Pseudomonas species or as a contaminant in a culture.[3]

Antibiotic resistance and susceptibility

The bacterium is susceptible to numerous

immunity to the bacterium is needed before a vaccine can be developed. Mice are fairly close to humans in their susceptibility to B. mallei and would be the ideal choice of animal for creating a model for the vaccine.[4]

Pathogenicity

Burkholderia mallei is responsible for causing

defensins and other pathogen-killing agents. MNGCs may help protect the bacteria from immune responses.[10] B. mallei's ability to live within the host cell makes developing a vaccine against it difficult and complex. The vaccine would need to create a cell-mediated immune response, as well as a humoral response to the bacteria in to be effective in protecting against B. mallei. In regards to a vaccine against B. mallei, the closeness of B. mallei to B. pseudomallei may make it possible that a vaccine developed for either type would be effective against the other.[7]

Symptoms of Burkholderia mallei infection

Horses

lesions, and nodules around the liver or spleen. Acute infection in horses results in a high fever, loss of fat or muscle, erosion of the surface of the nasal septum, hemorrhaging or mucus discharge. The bacterium mostly affects the lungs and airways.[4]
Human infection with B. mallei is rare, although it occasionally occurs among laboratory workers dealing with the bacteria or those who are frequently near infected animals.
symptoms that will result. If the bacteria enter through the skin, a local skin infection can result, while inhaling B. mallei can cause septicemic or pulmonary, muscular, hepatic, or splenous infections. B. mallei infection has a fatality rate of 95% if left untreated, and a 50% fatality rate in individuals treated with antibiotics.[4]

Cellular response to infection

In the first days of B. mallei infection,

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.[11]

MD-2 complex of innate immune system, dampening the host immune response and increasing the risk of bacterial dissemination.[12]

Global presence

Burkholderia 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.[4] 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.[13]

Potential as a biological weapon

Bukrholderia 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.[7] 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.[4] 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.[14]

Incidence in the United States

In March 2000, one of the first cases since the 1940s of glanders in the United States occurred in a young microbiologist working for the

fatigue, rigors, night sweats, and loss of weight. The next month, his symptoms seemed to disappear after treatment with clarithromycin, but after the medication was stopped, the symptoms reappeared. After conducting multiple tests on cultures from the researcher's blood and a biopsied portion of a liver abscess, the bacterium was identified as B. mallei. Once it was established what infected the researcher, another course of antibiotics was given (imipenem and doxycycline
) with 6 months of treatment. After a year, the researcher made a full recovery.

This incident also showed how a cut or skin

abrasion is not absolutely necessary to contract the disease, as the researcher had no recollection of any cut or accident while working in the laboratory. The case was significant as it showed the difficulty that microbiology laboratories have in identifying bioweapon agents and the potential consequences if measures are not taken to prepare for an actual biological attack.[13]

History as a weapon of biological warfare

Burkholderia mallei was intentionally used to infect animals and humans during World War I. The Germans used B. mallei to infect animals that were being sent from neutral countries to the Allies with glanders.[3] The Germans' plans for biological warfare started in 1915 on the East Coast of the United States; they intended to infect and kill the livestock that were being sent to the Allies and facilitate the transfer of the disease to humans. The East Coast was where many animals were being assembled for shipment to the Allies fighting in Europe. The Germans also targeted Romania, Norway, and Spain's animal supplies with cultures of glanders. The German biological sabotage eventually spread to Argentina, where agents would rely on bacterial cultures from Spain to infect the cattle, horses, and mules that Argentina was supplying to the Allies. The German use of microbes as weapons is one of the only documented attacks of intentionally using biological weapons against neutral countries.[15]

The Japanese used B. mallei in their biological warfare research units. The most notable and notorious unit, Unit 731, used the bacterium to conduct experiments on live human subjects. However, the Japanese did not end up creating a biological weapon out of B. mallei. They did actually use B. mallei to test its effectiveness in contaminating water supplies, and the results of these tests were successful.

The Russians' biological weapons program also took an interest in B. mallei and conducted field tests with it. Some of the researchers from the program were actually infected and killed by it during the course of their research. It has been suggested that the Soviet Union eventually used B. mallei during their war in Afghanistan against the mujahideen.[3]

See also

References

External links