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Salmonella Virulence and Drug Susceptibility
Mutations in the poxA gene or the
yjeK gene appear to be nearly
sity of Washington
This allows Salmonella to selectively change its levels of certain proteins to respond to inhospitable conditions.
Salmonella is adaptable and can withstand many of the body's attempts to fight it. The bacteria live and multiply in a special compartment inside the cells of an infected person or animal.
Salmonella's metabolism also changes over time to make use of the nutrients available in the host cell, and to survive damage from the build-up of oxidants and nitric oxide in the infected cell.
While screening mutant Salmonella that were resistant to a form of nitric oxide that normally stops the bacteria from dividing, Navarre, Professor Fang and their research collaborators found mutations in two little-known genes. These are the closely linked poxA and yjeK genes. In a number of bacteria, these two genes are associated with a third gene that encodes the Bacterial Elongation Factor P, which is involved in protein production.
The researchers discovered that these three genes operate in a common pathway that is critical for the ability of the Salmonella bacteria to cause disease and resist several classes of antibiotics. Salmonella with mutations in either the poxA gene or the yjeK genes, the study noted, appear to be nearly identical and show similar changes in proteins involved in metabolism.
Strains with mutations in both genes resemble the single mutant strains, an observation that suggests the two genes work in the same pathway.
The mutant strains exhibited many abnormalities under stressful conditions.
"The wide spectrum of compounds that dramatically inhibited the growth of these mutant strains suggest that the defect lies in a general stress response," the researchers noted. The mutant bacteria measurably differed from the wild-type Salmonella under 300 different conditions. In addition, their aberrant production of virulence factors reduces their ability to survive in the host.
The researchers' analysis also suggests that the way poxA and yjeK modify the bacterial protein elongation factor is essential in the production of proteins that allow the bacteria to use alternative energy sources when they are deprived of nutrients, as occurs after they enter host cells.
Unexpectedly the researchers found that the Salmonella with mutations in poxA and yjeK continued to respire inappropriately under nutrient-poor conditions in which wild-type Salmonella cease respiration.
MEDICA.de; Source: University of Washington