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.

Altered Outer Membrane Transcriptome Balance with AmpC Overexpression in Carbapenem-Resistant Enterobacter cloacae

“…Complemented strain represented an 8-fold decrease in MIC values of imipenem and a 128-fold decrease of cephalosporins and meropenem MIC values. Another project emphasizing key role of OmpF protein was published by Moya-Torres et al (2014). Authors performed molecular characterization of permeability disorders in Serratia marcescens , and proved that OmpF protein was the most important factor contributing to changes in MIC values of β-lactams.…”

Genome Assembly of Serratia marcescens Type Strain ATCC 13880

“…The species has the ability to infect plants, invertebrates, and vertebrates (1). Human infection, generally found in children and the immunocompromised, may include a variety of organ systems and is often resistant to common antibiotics (2, 3). The type strain sequenced here is used in many research and diagnostic applications as a control strain.…”

The Importance of Porins and β-Lactamase in Outer Membrane Vesicles on the Hydrolysis of β-Lactam Antibiotics

“…Choi and Lee (2019) demonstrated that the OmpF-defective E. coli mutants showed increased resistance to several β-lactam antibiotics, such as ampicillin, cefalotin, cefoxitin, ceftazidime, aztreonam, and imipenem [47]. The absence of OmpF classical porin resulted in a significant increase in β-lactam resistance, including ampicillin and cefoxitin [51]. Our findings corroborate previous reports that the MIC against several β-lactam antibiotics was decreased or increased in single isogenic β-lactamase or porin mutants, respectively (Table 1).…”

“…OmpC and OmpF are considered as the leading transport porins that assist penetration of most β-lactam antibiotics [47,[51][52][53], and both porins are known to be major protein components of E. coli OMVs [54]. Diffusion rates through these channels differ according to a substance's molecular weight and electrical charge [48,55].…”