Assessment of cooperative antibiotic resistance of Salmonella Typhimurium within heterogeneous population

Abstract

This study was designed to investigate the cooperative resistance in the mixed culture of antibiotic-sensitive and antibiotic-resistant Salmonella Typhimurium. Strains of S. Typhimurium ATCC 19585 (ST^S) and clinically isolated antibiotic-resistant S. Typhimurium CCARM 8009 (ST^R) grown in single and mixture with 1 × MIC ceftriaxone (CEF) were used to determine the viability, β-lactamase activity, and gene expression. The MIC₅₀ values of ST^R to CEF was increased by more than 5-fold with increasing inoculum densities from 10² to 10⁷ CFU/mL. ST^S was resistant to 1 × MIC CEF in the mixed culture of ST^S and ST^R, showing the more than 10⁸ CFU/mL after 20 h of incubation at 37 °C. The highest β-lactamase activity was 18 μmol/min/mL in the mixed culture, corresponding to the highest relative expression of β-lactamase-related genes (bla_TEM). These results shed new light on the cooperative resistance of antibiotic-sensitive bacteria within a heterogeneous population including β-lactamase-producing bacteria.

Keywords: Ceftriaxone; Cooperative resistance; Inoculum effect; Salmonella; β-Lactamase.