Sunday, September 28, 2008

What are Burkholderia?


Definition


Burkholderia are gram-negative, motile, non-spore-forming, obligately aerobic rods, some of which can be pathogenic in animals and plants. They have worldwide distribution in soils and in groundwater.






Natural Habitat and Features

The genus Burkholderia was named for plant pathologist and microbiologist Walter Burkholder in 1992. Before this date, most members of this genus were classified as Pseudomonas spp.


All Burkholderia spp. are gram-negative, motile,
non-spore-forming, obligately aerobic rods. Although usually nonencapsulated, they
do form polysaccharide capsules at low pH (acidity). They are distributed from the
Arctic to the tropics, and are especially common in damp soils, ground water, and
stagnant pools. The genus contains animal and plant pathogens and
saprobic species, some of which can be opportunistic pathogens. They are easily
grown on most common laboratory media, although many strains need forty-eight to
seventy-two hours before growth is visible on agar.



Burkholderia have the largest genomes of any known soil bacterium, with three chromosomes and a minimum of one large plasmid. Various strains, especially of xenovorans, have diverse metabolic pathways that allow the bacteria to degrade polycyclic aromatic compounds such as naphthalene, halogenated hydrocarbons such as trichloroethylene and polychlorinated biphenyls (PCBs), and chloroorganic pesticides such as 2,4-D.


Nonpathogenic strains have been engineered by knocking out genes needed for
pathogenicity. These strains are used for bioremediation of sites contaminated with PCBs and other
organics. Several studies have been carried out to see how this degradative
ability can be enhanced in situ and in laboratory-based bioreactors. Many
cepacia strains secrete antimicrobials and antifungals. These
strains have been used as biocontrols of plant diseases, although pathogenicity
has limited their use.


Pathogenic strains of Burkholderia were among the first bioweapons used in modern warfare when Germany attempted to use
mallei, the equine pathogen that causes glanders, in
an attempt to destroy the horses on which enemy cavalries depended in World War I.
Both mallei and pseudomallei are considered
possible biowarfare and bioterrorism agents. In the 1980’s, the
Soviet Union was thought to have produced more than two thousand tons of dried
mallei preparation, which could be used in biological
weapons.




Pathogenicity and Clinical Significance

Several Burkholderia spp. can infect humans. Mallei primarily causes glanders in equids, but humans and other animals can serve as accidental hosts. In humans, symptoms vary but often include skin and respiratory mucosal lesions, pneumonia, spleen and liver abscesses, muscle aches, and general malaise. Even when treated, mortality approaches 50 percent. In the United States, human glanders is now only seen among those who work with the bacteria, but in other parts of the world, especially tropical regions of Asia, human infections are more common and can be contracted directly from infected animals. Human-to-human transfer is rare.



Pseudomallei causes melioidosis, also called Whitmore’s disease, in humans and other animals. It is usually transmitted through direct contact with contaminated soil or water through abrasions, inhalation, or ingestion. The disease is mainly found in tropical areas and is endemic to southeastern Asia and northern Australia. The most common symptoms are respiratory and can range from mild bronchitis to severe pneumonia. Localized skin infections are also seen when the route of entry is through an abrasion.


Although rare in healthy adults, systemic and disseminated melioidosis
can occur in debilitated and immune compromised persons. It is also more common in
those with diabetes mellitus. The disease can become chronic and lead
to multiple abscesses on internal organs or on the skin. Untreated, the disease
has 100 percent mortality; among those treated, mortality is 40 percent. Because
many of the symptoms mimic other diseases, melioidosis is not always diagnosed
immediately and, thus, has a chance to become more serious.


Members of the cepacia complex, a group of nine similar
species including multivorans, cenocepacia,
stabilis, vietnamiensis,
dolosa, ambifaria, anthina,
and pyrrocinia, have a very low pathogenicity in healthy humans,
but they are significant pathogens in persons with cystic
fibrosis and in those who are immune compromised. Unlike
mallei and pseudomallei, these strains are
usually transmitted by direct human-to-human contact.
Multivorans, however, seems to be most commonly acquired from an
environmental source. The most common symptom of a cepacia
complex infection is pneumonia, although urogenital, surgical-wound, and
catheter-related hospital infections are known to occur.




Drug Susceptibility

Many antibiotics, including ceftazidime, imipenem, meropenem,
doxycycline, penicillin, piperacillin,amoxicillin-clavulonic acid, amiloride,
tobramycin, and aztreonam, have been used to treat Burkholderia
infections. In all cases, ten to fourteen days of intravenous (IV) antibiotic
infusion is usually followed by three to six months of oral antibiotic
therapy.


For severe cases, the oral therapy can include a combination of antibiotics and can last up to one year. In disseminated infections, the surgical removal of abscesses is sometimes necessary. Persons with cystic fibrosis who have a cepacia complex infection will need three to six months of aerosolized antibiotics, often a combination of amiloride and tobramycin. This regimen is usually preceded by an IV antibiotic infusion comprising tobramycin, meropenem, and ceftazidime. Many strains of mallei are more susceptible to antibiotics than are strains of pseudomallei or cepacia complex and, thus, do not need lengthy antibiotic treatment.




Bibliography


Coenye, Tom, and Peter Vandamme, eds. Burkholderia: Molecular Microbiology and Genomics. Wymondhan, England: Horizon Bioscience, 2006. The first two chapters give a comprehensive review of the genus. Later chapters look at the genus from the perspective of biochemistry and genetics.



Krieg, Noel R., et al., eds. Bergey’s Manual of Systematic Bacteriology. 2d ed. New York: Springer, 2010. Volume 2 of this multivolume work describes the Proteobacteria in detail.



Madigan, Michael T., and John M. Martinko. Brock Biology of Microorganisms. 12th ed. Upper Saddle River, N.J.: Pearson/Prentice Hall, 2010. This text outlines many common bacteria and describes their natural history, pathogenicity, and other characteristics.



Romich, Janet A. Understanding Zoonotic Diseases. Clifton Park, N.Y.: Thomson Delmar, 2008. A good introduction to zoonotic diseases, including glanders and melioidosis.

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