Development of de novo resistance in Salmonella Typhimurium treated with antibiotic combinations

Jirapat Dawan; Md Jalal Uddin; Juhee Ahn

doi:10.1093/femsle/fnz127

Development of de novo resistance in Salmonella Typhimurium treated with antibiotic combinations

FEMS Microbiol Lett. 2019 May 1;366(10):fnz127. doi: 10.1093/femsle/fnz127.

Authors

Jirapat Dawan¹, Md Jalal Uddin¹, Juhee Ahn¹

Affiliation

¹ Department of Medical Biomaterials Engineering and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.

PMID: 31183498
DOI: 10.1093/femsle/fnz127

Abstract

This study was designed to evaluate the evolution of antibiotic resistance in Salmonella enterica serovar Typhimurium treated with the combination of antibiotics. The experimental evolution of antibiotic resistance of S. Typhimurium was evaluated either under single antibiotic (kanamycin, KAN; penicillin, PEN; erythromycin, ERY) or in combination of two antibiotics (KAN + PEN or KAN + ERY) as measured by fractional inhibitory concentrations (FICs), stepwise resistance selection, cross-resistance evaluation, resistance fitness and relative gene expression. KAN + PEN and KAN + ERY showed the synergistic effect against S. Typhimurium (FIC index < 0.5). KAN + ERY delayed the induction of de novo mutations in S. Typhimurium. The cross-resistance of S. Typhimurium to all antibiotics except ERY and tetracycline was observed in KAN and PEN alone. The fitness cost was lower in single antibiotic treatments than combinations. The highest relative fitness was 0.91 in PEN, followed by KAN (0.84) and ERY (0.78), indicating the low fitness costs in single antibiotic treatments. The overexpression of efflux pump-related genes (acrA and acrB), outer membrane-related gene (ompC) and adherence-related gene (csgD) were observed in the single antibiotic treatments. Our results suggest that KAN + PEN and KAN + ERY could be used as a potential therapeutic treatment by decreasing the evolution of antibiotic resistance in S. Typhimurium and reusing conventional antibiotics.

Keywords: Salmonella; antibiotic combination; antibiotic resistance; cross-resistance; fitness cost.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology*
Directed Molecular Evolution
Drug Resistance, Multiple, Bacterial / genetics*
Gene Expression
Genetic Fitness / drug effects*
Microbial Sensitivity Tests
Salmonella typhimurium / drug effects*
Salmonella typhimurium / genetics*

Substances

Anti-Bacterial Agents