Associations between antibiotic resistance and bacteriophage resistance phenotypes in laboratory and clinical strains of Salmonella enterica subsp. enterica serovar Typhimurium

Abstract

Bacteriophages have received great attention as an alternative over antibiotics due to the host specificity. Therefore, this study was designed to evaluate the associations between bacteriophage-insensitive (BI) and antibiotic-resistant mutants of Salmonella Typhimurium strains. Bacteriophage-sensitive (BS) Salmonella enterica serovar Typhimurium ATCC 19585 (BSST^WT), ciprofloxacin-induced S. Typhimurium ATCC 19585 (BSST^CIP), S. Typhimurium KCCM 40253 (BSST^LAB), and clinically isolated multidrug-resistant S. Typhimurium CCARM 8009 (BSST^MDR) were used to induce the bacteriophage-insensitive mutants (BIST^WT, BIST^CIP, BIST^LAB, and BIST^MDR), which were characterized by measuring mutant frequency lysogenic induction, phage adsorption, antibiotic susceptibility, and differential gene expression. The numbers of BSST^WT, BSST^CIP, and BSST^LAB were reduced by P22 (>3 log), while the least lytic activity was observed for BSST^MDR, suggesting alteration in bacteriophage-binding receptors on the surface of multidrug-resistant strain. BSST^WT treated with P22 showed the large variation in the cell state (CV>40%) and highest mutant frequency (62%), followed by 25% for BSST^CIP. The least similarities between BSST^WT and BIST^WT were observed for P22 and PBST-13 (<12%). The relative expression levels of bacteriophage-binding receptor-related genes (btuB, fhuA, fliK, fljB, ompC, ompF, rfaL, and tolC) were decreased in BIST^CIP and BIST^MDR. These results indicate that the bacteriophage resistance is highly associated with the antibiotic resistance. The findings in this study could pave the way for the application of bacteriophages as an alternative to control antibiotic-resistant bacteria.

Keywords: Antibiotic resistance; Bacteriophage; Bacteriophage-binding receptor; Gene expression; Salmonella.