Metabolic and genotypic characterization of meropenem-susceptible and meropenem-resistant Serratia marcescens isolates.

Abstract

Background/aim: Serratia marcescens which is a nosocomial pathogen, is naturally resistant to a wide spectrum of antibiotics, which makes the management of infections difficult. The aim of this study was to determine the in vitro susceptibilities of S. marcescens to ceftriaxone, ceftazidime, meropenem, amikacin, gentamicin, ciprofloxacin, and to compare the metabolic profiles of meropenem-resistant isolates under basal conditions and after exposure to sublethal concentrations of meropenem.

Materials and methods: A total of 84 S. marcescens isolates were included from various samples. Genes for meropenem resistance were determined by polymerase chain reaction (PCR). Genetic similarities among isolates of S. marcescens were investigated by pulsed-field gel electrophoresis (PFGE). MIC changes of meropenem were investigated in the presence of the resistance-nodulation-cell division (RND) type pump inhibitor phenylalanyl-arginyl-β-naphthylamide (PAβN) and proton ionophore (uncoupler) carbonyl cyanide m-chlorophenylhydrazone (CCCP). A GC/MS-based metabolomics approach was implemented to determine the differentiation of metabolome structure. We examined the adaptive responses of isolates, characterized by resistance or susceptibility, under conditions of meropenem-induced stress.

Results: The highest resistance rate was observed for ceftriaxone (27.6%). Amikacin was the most effective drug, with a resistance rate of 6.9%. Overall, 10 (11.9%) isolates were resistant to meropenem. Genotyping of β-lactamase genes revealed that bla _OXA-48 was present in one isolate. In total, efflux pump activity was detected in four isolates. The GC/MS-based metabolomics analysis revealed alterations in nucleotide and pyrimidine metabolism, as well as in ATP-binding cassette (ABC) transporter pathways, between the meropenem-susceptible and meropenem-resistant groups.

Conclusion: Understanding the metabolic profiles of S. marcescens could facilitate the development of novel diagnostic approaches and antimicrobial strategies in the ongoing global effort to combat meropenem-resistant S. marcescens.