Combining genetic screening with pathogenicity testing in mice, a recent study reports the progress of a research group seeking to tap the mysteries of Burkholderia pseudomallei—and may lead to a vaccine or other treatment against this deadly bacterium.

The developing world is rife with infectious pathogens all but unknown in the United States and other developed nations. B. pseudomallei is one such dangerous pathogen, for which there is no vaccine, no reliable treatment, and a dearth of information about its pathogenesis. B. pseudomallei causes melioidosis in mammals, a disease endemic to Southeast Asia and characterized by symptoms that vary from fever, pneumonia, and body aches to parotid abscesses and neurological abnormalities. Many experts believe that B. pseudomallei's ability to colonize most of the body's organs, coupled with its intrinsic resistance to many antibiotics, make it a natural candidate for bioterrorism. The physiological sources of the bacterium's virulence are still largely unknown.

For that reason, Brendan Wren at the London School of Hygiene and Tropical Medicine (London, England) and his colleagues modified a technique called signature-tagged mutagenesis (STM) to aid in the identification of virulent genes in the B. pseudomallei genome. In essence, STM uses transposons to randomly insert short gene sequences into a bacterial genome, creating mutants that researchers screen for pathogenicity. Presumably, mutants with attenuated virulence have transposon inserts in genes involved in the pathogenesis of B. pseudomallei.

Wren and his coworkers created 892 such mutants in B. pseudomallei and tested these mutants for virulence in female BALB/c mice (Infect. Immun., March). They identified 39 attenuated mutants, of which one had a transposon insertion in the aroB gene, which encodes an enzyme in the shikimate metabolic pathway. Wren's group then attempted to vaccinate mice with this attenuated mutant strain of B. pseudomallei—dubbed mutant 13B11—against wildtype B. pseudomallei. Although this novel vaccine did not ultimately protect the mice against B. pseudomallei infection, the treatment did increase the survival time of the vaccinated mice.

Such progress is encouraging, but hopefully only the first steps of many. “We continue to study the protective efficacy of other mutants identified as live attenuated vaccines during our study,” Wren tells Lab Animal. “The shikimate pathway,” he continues, “is missing in mammals, meaning that drugs targeting dehydroquinate synthase (the product of the aroB gene disrupted in mutant 13B11) may be of use in the treatment of melioidosis.”