Quorum sensing-induced phenotypic switching as a regulatory nutritional stress response in a competitive two-species biofilm: An individual-based cellular automata model.

Competition for nutrients in a polymicrobial biofilm may lead to susceptible species being subjected to nutritional stress. The influence of bacterial growth rates and interspecies interactions on their susceptibility and response to nutritional stress is not well understood. and are two prevalent causative pathogens that coexist in biofilm-associated infections. Despite being the slower-growing species, dominates in a two-species biofilm by inducing phenotypic switching of S. aureus to a metabolicallychallenged small colony variant (SCV) via the release of 2-heptyl-4-hydroxyquinoline N-oxide (HQNO). We hypothesize that experiences nutritional stress in competition with S. aureus, and that the release of HQNO is an adaptive response to nutritional stress.We present an individual-based two-species biofilm model in which interactions between entities induce emergent properties. As the biofilm matured, the difference in growth rates of the two species caused a non-uniform distribution of nutrients leading to nutritional stress for P. aeruginosa and a concurrent increase in the proportion of subpopulation. The latter resulted in increased release of autoinducer, and subsequently the upregulation of cells via quorum sensing. Upregulated P. aeruginosa cells released HQNO at enhanced rates, thereby inducing phenotypic switching of to SCVs which consume nutrient at a reduced rate. This shifted the nutrient distribution back in favor of , thereby relieving nutritional stress. Increase in nutritional stress potentiated the transformation of into SCVs. HQNO production decreased once nutritional stress was relieved, indicating that phenotypic switching acts as a regulatory stress-adaptive response.