title: The lack of OmpF, but not OmpC, contributes to increased antibiotic resistance in Serratia marcescens.
abstract: The environmental organism Serratia marcescens is one of the primary causes of numerous nosocomial outbreaks and opportunistic infections. Multi-drug resistance is now a common feature among S. marcescens clinical isolates, complicating the efficacy of treatment. Recent reports have attributed antibiotic resistance to altered porin expression as well as perturbation of the intrinsic AmpC beta-lactamase production pathway. In this study, we aimed to genetically correlate the absence of OmpF and OmpC classical porins with increased antibiotic resistance. In generating isogenic porin mutant strains, we avoided incorporating additional resistance through the use of antibiotic cassettes in gene replacement and adopted an alternative strategy in creating clean unmarked mutant strains. We found that lack of OmpF, but not OmpC, significantly increased antibiotic MIC values to the beta-lactam drugs such as ampicillin and cefoxitin as well as to nitrofurantoin. Furthermore, we found that cefoxitin did not induce intrinsic AmpC beta-lactamase production, indicating that the increased MIC values were a result of reduced permeability of cefoxitin due to the lack of OmpF. Genetic deletion of both ompF and ompC did not compromise the integrity of the bacterial cell envelope in optimal growth conditions, suggesting that other outer-membrane porins may function in a compensatory role to facilitate nutrient uptake and cell envelope integrity. Taken together, to our knowledge this is the first study that genetically correlates increased antibiotic resistance with altered porin expression in S. marcescens.
authors.affiliation: Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada.
authors.forename: Aniel
authors.initials: A
authors.lastname: Moya-Torres
authors.affiliation: National Microbiology Laboratory, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Mulvey
authors.affiliation: Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada.
authors.forename: Ayush
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada.
authors.forename: Ivan J
authors.initials: IJ
authors.lastname: Oresnik
authors.affiliation: Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada.
authors.forename: Ann Karen C
authors.initials: AKC
authors.lastname: Brassinga
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002440:Cefoxitin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D017353:Gene Deletion; D008826:Microbial Sensitivity Tests; D009582:Nitrofurantoin; D018272:Porins / Q000235:genetics* / Q000378:metabolism*; D012706:Serratia marcescens / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; C113724:OmpC protein; C109237:OmpF protein; D018272:Porins; D002440:Cefoxitin; D000667:Ampicillin; D009582:Nitrofurantoin