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Abstract
Pseudomonas aeruginosa is of increasing concern in hospital settings because of frequently emerging antibiotic resistant strains implicated in nosocomial infections. There exists a complex network of gene expression regulatory mechanisms that contribute to decreased susceptibility of P.aeruginosa to difference classes of antibiotics. One protein recently shown to be involved in antibiotic resistance to ciprofloxacin is Lon, a protease that degrades misfolded proteins in addition to upregulating a number of stress response genes. In this study, RpoS and DnaK, two downstream targets of Lon, were assessed to determine their contribution to antibiotic susceptibility. RpoS is a transcriptional regulator involved in surviving various environmental conditions. DnaK is a chaperone that binds to nascent polypeptides to prevent protein misfolding, a function similar to that of Lon. We investigated the kinetics through which RpoS and DnaK affect susceptibility to ciprofloxacin by way of minimal inhibitory concentration (MIC) and time-dependent killing assays. Results indicate no significant difference in MIC but enhanced sensitivity to ciprofloxacin in dnaK strains contrasted by delayed susceptibility in rpoS mutants by a survival difference of 15%. Taken together, these results suggest that DnaK is involved in transient ciprofloxacin tolerance but global resistance to antibiotics is mediated by complex gene regulatory networks that may not be entirely dependent on RpoS.