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Published on: March 3, 2023
Metabolic and genotypic characterization of meropenem-susceptible and meropenem-resistant Serratia marcescens
Şeyma Nigiz1, Gülşen Hazirolan2, Gülşen Altinkanat Gelmez3
1Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkiye.
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.
Insights
Serratia marcescens exhibits high resistance to antibiotics like ceftriaxone. Meropenem-resistant strains show altered metabolic profiles, particularly in nucleotide and pyrimidine pathways, offering targets for new antimicrobial strategies.
Area of Science:
- Microbiology
- Infectious Diseases
- Metabolomics
Background:
- Serratia marcescens is a significant nosocomial pathogen known for intrinsic antibiotic resistance.
- Managing infections caused by S. marcescens is challenging due to its resistance patterns.
Purpose of the Study:
- To determine the in vitro antibiotic susceptibilities of S. marcescens isolates.
- To compare metabolic profiles of meropenem-resistant S. marcescens under different conditions.
Main Methods:
- Antibiotic susceptibility testing against various drugs.
- Polymerase chain reaction (PCR) for meropenem resistance genes.
- Gas Chromatography-Mass Spectrometry (GC/MS) based metabolomics.
Main Results:
- Ceftriaxone showed the highest resistance rate (27.6%); amikacin was most effective (6.9% resistance).
- 11.9% of isolates were resistant to meropenem, with one carrying blaOXA-48.
- Metabolomics revealed significant alterations in nucleotide, pyrimidine, and ABC transporter pathways in meropenem-resistant isolates.
Conclusions:
- Understanding S. marcescens metabolic profiles can guide novel diagnostic and therapeutic strategies.
- Targeting metabolic pathways may help combat meropenem-resistant strains.
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