Associations between antibiotic resistance and bacteriophage resistance phenotypes in laboratory and clinical strains of Salmonella enterica subsp. enterica serovar Typhimurium. (June 2020) - Uddin, Md Jalal
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. Highlights: The P22-induced ciprofloxacin-resistant Salmonella mutant showed multiple resistance to P22-B1, PBST-32, and PBST-35. The superinfection exclusion occurred at P22-induced Salmonella mutants. The adsorption rates did not correspond to the lytic activities of P22-1, P22-B1, and PBST-13 against Salmonella Typhimurium. The antibiotic susceptibilities were increased in the phage-insensitive Salmonella Typhimurium.