Synergistic efficacy of phage Henu10 with antibiotics against Shigella dysenteriae with insight into phage resistance and fitness trade-offs
Jing Zhao, Baohong Chen, W. Wang, Yu Ri Kang, Emily Hu, Yuan Zhang, Huiling Chen, Xiao Xu, Xin‐Ying Ji, Yuhan Wang, Tieshan Teng, Salwa E. Gomaa
Abstract
Introduction The irrational use of antibiotics has facilitated the emergence of multidrug- resistant Shigella spp ., undermining the effectiveness of the currently available antibiotics. Consequently, there is an urgent need to explore new approaches, with phage therapy emerging as a promising alternative. Methods In this study, we isolated a phage targeting Shigella dysenteriae from sewage samples using DLA methold, designated Henu10. The morphology, biological characteristics, genomic composition, and phylogenetic relationships of Henu10 were thoroughly characterized. To investigate the trade-off relationship between phage resistance and bacterial fitness, phage Henu10-resistant strains R6 and R11 were identified using continuous passage and bidirectional validation methods. Results Phage-resistant strains R6 and R11 exhibited impaired adsorption, increased sensitivity to temperature and pH stress, heightened susceptibility to certain antibiotics (such as ciprofloxacin and kanamycin), reduced biofilm-forming capacity, and diminished colonization ability in vivo compared to the wild-type strain. Discussion These results indicate that phage Henu10 may effectively control the pathogenic bacteria associated with S. dysenteriae , representing a promising new therapeutic option for treating S. dysenteriae infections.