Fitness Trade-Offs in Phage Cocktail-Resistant Salmonella enterica Serovar Enteritidis Results in Increased Antibiotic Susceptibility and Reduced Virulence
Dongyang Gao, Hongyue Ji, Linkang Wang, Xinxin Li, Xinxin Li, Dayue Hu, Junna Zhao, Shuang Wang, Tao Pan, Xiangmin Li, Xiangmin Li, Ping Qian
Abstract
experiments. Importantly, we found that pressure from phage cocktails with different receptors can drive phage-resistant bacterial mutants to evolve in a direction that entails more severe fitness costs, resulting in reduced virulence and increased susceptibility to antibiotics. These findings suggest that phage cocktail therapy using combinations of phages targeting different important receptors (e.g., LPS or the efflux pump AcrAB-TolC) on the host surface can steer the host bacteria toward more detrimental surface mutations than single-phage therapy, resulting in more favorable therapeutic outcomes.
Topics & Concepts
VirulenceSalmonella entericaMicrobiologyBiologyMutantBacteriophagePhage therapySalmonella enteritidisBacterial outer membraneSalmonellaAntibiotic resistancePhage displayAntibioticsBacteriaEscherichia coliGeneGeneticsAntibodyBacteriophages and microbial interactionsViral gastroenteritis research and epidemiologySalmonella and Campylobacter epidemiology