Mucin modulates phage infection dynamics and biofilm formation in enteropathogenic Yersinia enterocolitica

Mucosal barriers serve as a multifunctional interface and nutrient-rich habitat for diverse microbes, including bacteria and bacteriophages. Some phages can bind to mucin glycoproteins via carbohydrate-interacting modules and provide an additional layer of mucosal immunity by shielding the underlying epithelium from invading bacteria. However, the role of mucins in shaping phage-bacterium interactions remains poorly understood. We investigated dynamics between highly pathogenic Yersinia enterocolitica serotype O:8 and its mucus-adherent phage fMtkYen801 under the in vitro mucosal environment. We assessed how mucin supplementation, varying phage doses, nutrient and temperature conditions influence phage-bacterium dynamics and biofilm development. We found that bacterial pre-exposure to mucins led to enhanced phage replication, with a 2-log increase in phage titers. Mucins also modulated post-infection growth dynamics and reduced biofilm formation in the host bacteria. Genomic analysis of phage resistant bacterial variants revealed mutations in virulence, quorum sensing and antibiotic resistance genes in both mucin enrichment and control groups, suggesting potential fitness tradeoffs during resistance evolution. These findings highlight the role of mucosal environments in shaping phage-host interactions in Y. enterocolitica, a significant enteric pathogen, and emphasize the need for investigating these dynamics under complex, physiologically relevant systems to inform better phage therapy strategies against mucosal bacterial infections.