Mucin modulates phage infection dynamics and biofilm formation in enteropathogenic <i>Yersinia enterocolitica</i>

Abstract 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 the dynamics between highly pathogenic Yersinia enterocolitica serotype O:8 and its mucus-adherent phage fMtkYen801 under in vitro mucosal environment. We assessed how mucin supplementation, varying phage doses, nutrient and temperature conditions influence phage-bacterium dynamics and biofilm formation. We found that pre-exposure to mucins led to enhanced phage replication in the bacterial host, with a 2-log increase in phage titers, and high abundance of surviving bacteria. Interestingly, mucin glycoproteins also provided Y. enterocolitica a nutrient source and a chemical cue to modulate its growth and biofilm biogenesis. 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. Collectively, these findings highlight the importance of mucosal surfaces as an important ecological driver of 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.