TY - JOUR
T1 - Positive adaptive state
T2 - Microarray evaluation of gene expression in Salmonella enterica typhimurium exposed to nalidixic acid
AU - Dowd, Scot E.
AU - Killinger-Mann, Karen
AU - Blanton, John
AU - San Francisco, Michael
AU - Brashears, Mindy
PY - 2007/6
Y1 - 2007/6
N2 - The emergence of antimicrobial resistance among foodborne bacteria associated with food animal production is an important global issue. We hypothesised that antibiotics generate a positive adaptive state in Salmonella that actively contributes to the development of antimicrobial resistance. This is opposed to common views that antimicrobials only act as a passive selective pressure. Microarray analysis was used to evaluate changes in gene expression that occur upon exposure of Salmonella enterica Typhimurium ATCC 14028 to 1.6 μg/mL of nalidixic acid. The results showed a significant (P < 0.02) difference (fold expression differences >2.0) in the expression of 226 genes. Comparatively repressed transcripts included Salmonella pathogenicity islands 1 and 2 (SPI1 and SPI2). Induced genes included efflux pumps representing all five families of multidrug-resistance efflux pumps, outer membrane lipoproteins, and genes involved in regulating lipopolysaccharide chain length. This profile suggests both ehanced antimicrobial export from the cell and membrane permeability adaptations to limit diffusion of nalidixic acid into the cell. Finally, increased expression of the error-prone DNA repair mechanisms were also observed. From these data we show a highly integrated genetic response to nalidixic acid that places Salmonella into a positive adaptive state that elicits mutations. Evaluation of gene expression profile changes that occur during exposure to antibiotics will continue to improve our understanding of the development of antibiotic resistance.
AB - The emergence of antimicrobial resistance among foodborne bacteria associated with food animal production is an important global issue. We hypothesised that antibiotics generate a positive adaptive state in Salmonella that actively contributes to the development of antimicrobial resistance. This is opposed to common views that antimicrobials only act as a passive selective pressure. Microarray analysis was used to evaluate changes in gene expression that occur upon exposure of Salmonella enterica Typhimurium ATCC 14028 to 1.6 μg/mL of nalidixic acid. The results showed a significant (P < 0.02) difference (fold expression differences >2.0) in the expression of 226 genes. Comparatively repressed transcripts included Salmonella pathogenicity islands 1 and 2 (SPI1 and SPI2). Induced genes included efflux pumps representing all five families of multidrug-resistance efflux pumps, outer membrane lipoproteins, and genes involved in regulating lipopolysaccharide chain length. This profile suggests both ehanced antimicrobial export from the cell and membrane permeability adaptations to limit diffusion of nalidixic acid into the cell. Finally, increased expression of the error-prone DNA repair mechanisms were also observed. From these data we show a highly integrated genetic response to nalidixic acid that places Salmonella into a positive adaptive state that elicits mutations. Evaluation of gene expression profile changes that occur during exposure to antibiotics will continue to improve our understanding of the development of antibiotic resistance.
UR - http://www.scopus.com/inward/record.url?scp=34447272244&partnerID=8YFLogxK
U2 - 10.1089/fpd.2006.0075
DO - 10.1089/fpd.2006.0075
M3 - Article
C2 - 17600486
AN - SCOPUS:34447272244
SN - 1535-3141
VL - 4
SP - 187
EP - 200
JO - Foodborne Pathogens and Disease
JF - Foodborne Pathogens and Disease
IS - 2
ER -