Phage resistance-mediated trade-offs with antibiotic resistance in Salmonella Typhimurium

Abstract

This study was designed to evaluate the trade-offs between phage resistance and antibiotic resistance of Salmonella Typhimurium (STKCCM) exposed to bacteriophage PBST10 and antibiotics (ampicillin and ciprofloxacin). STKCCM was serially exposed to control (no PBST10/antibiotic added), phage alone, ampicillin alone, ampicillin with phage, ciprofloxacin alone, and ciprofloxacin with phage for 8 days at 37 °C. The treated cells were used to evaluate the antibiotic susceptibility, β-lactamase activity, relative fitness, gene expression, and phage-resistance frequency. The antibiotic susceptibility of STKCCM to ampicillin was increased in the presence of phages. The β-lactamase activity was significantly increased in the phage alone and ampicillin with phage. The combination treatments of phages and antibiotics resulted in a greater fitness cost. The efflux pump-associated tolC was suppressed in STKCCM exposed to phage alone. The highest phage-resistance frequencies were observed at phage alone, followed by ampicillin with phage and ciprofloxacin with phage. The tolC-suppressed cells showed the enhanced antibiotic susceptibility. This study provides useful information for designing effective phage-antibiotic combination treatments. The evolutionary trade-offs of phage-resistant bacteria with antibiotic resistance might be good targets for controlling antibiotic-resistant bacteria.