Novel Mechanism Found to Affect Salmonella Virulence

Just what makes Salmonella so adaptable and elusive? Scientists at the University of Washington have discovered a mechanism that may explain part of the organism’s ability to respond to inhospitable conditions. By selectively altering its production of proteins in a manner not previously recognized, Salmonella can change both its susceptibility to antibiotics and its level of virulence.

While screening mutant Salmonella that were resistant to a form of nitric oxide that normally stops the bacteria from dividing, researchers found mutations in two little-known genes, the closely linked poxA and yjeK genes. Senior author Ferric Fang, PhD, professor of microbiology and laboratory medicine and adjunct professor of medicine at the University of Washington in Seattle, said these two genes are associated with a third gene that encodes the bacterial elongation factor P, which is involved in protein production.

The findings were published July 29 in Molecular Cell (39(2):222-233).

Dr. Fang and his team found that these three genes work together in a common pathway key to Salmonella’s ability to cause disease while resisting some common classes of antibiotics. Mutant strains of these genes inhibited the growth of Salmonella, and the mutant varieties differed measurably from wild-type Salmonella under some 300 different conditions. An unexpected finding: Salmonella with mutations in poxA and yjeK continued to respire under nutrient-poor conditions in which wild-type Salmonella ceased respiration, suggesting that these genes help the bacteria respond appropriately to environmental stress.

“Although we didn’t set out to find something practical, I do feel that the more we understand about the physiology of pathogenic bacteria like Salmonella, the more we can exploit that physiology to reduce the likelihood of Salmonella infections,” Dr. Fang said. “We found that this system affects resistance to a lot of physical agents, antibiotics of different classes, and virulence, which tells you that you’re finding out something pretty deep down and basic about the organism.”