Characterization of phage evolution and phage resistance in drug-resistant Stenotrophomonas maltophilia

Abstract

Phage therapy is a promising approach to treat infections caused by drug-resistant Stenotrophomonas maltophilia (S. maltophilia) . However, the rapid development of phage resistance has hindered the therapeutic application of phages. In vitro evolutionary studies of bacteria–phage co-cultures can elucidate the mechanism of resistance development between phage and its host. In this study, we investigated the resistance trends between S. maltophilia and its phage and found that inhibition of phage adsorption is the primary strategy by which bacteria resist phage infection in vitro , while phages can re-infect bacterial cells by identifying other adsorption receptors. Although the final bacterial mutants were no longer infected by phages, they incurred a fitness cost that resulted in a significant reduction in virulence. In addition, the combination treatment with phage and aminoglycoside antibiotics could prevent the development of phage resistance in S. maltophilia in vitro . These findings contribute to increasing the understanding of the co-evolutionary relationships between phages and S. maltophilia .