Adaptive trade-offs between bacteriophage and antibiotic resistance in Salmonella Typhimurium

This study was designed to evaluate the phenotypic properties of PBST35-resistant Salmonella enterica subsp. enterica serovar Typhimurium in association with adaptive trade-offs between bacteriophage resistance and antibiotic resistance. Bacteriophage-insensitive S. enterica Typhimurium (BIST) variants were isolated and analyzed using the spot test, adsorption assay, and biofilm formation assay. The effects of bacteriophage and antibiotic combinations were evaluated using the disk diffusion assay, antibiotic susceptibility assay, and checkerboard assay to evaluate synergy. PBST35 bacteriophage showed a latent period of 10 min, a burst period of 50 min, and a burst size of 72 PFU/CFU. The swimming motility of BIST decreased significantly to 4 %, compared to 70 % in bacteriophage-sensitive S. enterica Typhimurium (BSST). BIST showed increased susceptibility to cefotaxime (CTX), ceftriaxone (CRO), meropenem (MEM), ciprofloxacin (CIP), levofloxacin (LEV), kanamycin (KAN), chloramphenicol (CHL), and sulfamethoxazole/trimethoprim (SXT). The MIC values of CTX, CIP, gentamicin (GEN), and polymyxin B (PMB) against BIST decreased by 2-fold, 1-fold, 2-fold, and 2-fold, respectively. The fractional inhibitory concentration (FIC) indices for BIST were 0.5 for CTX, 1.0 for CIP, 0.5 for GEN, and 0.5 for PMB. The sequential treatment of GEN and PBST35 reduced BSST biofilms by 87 % and BIST biofilms by 68 %. This study provides the potential of combining bacteriophages with antibiotics as a promising strategy to overcome resistance in bacteriophage-resistant strains and supports the development of integrated antimicrobial approaches to combat the growing threat of multidrug-resistant bacterial infections.