Quorum sensing-induced phenotypic switching as a regulatory nutritional stress response in a competitive two-species bio
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Indian Academy of Sciences (0123456789().,-volV) (0123456789().,-volV)
Quorum sensing-induced phenotypic switching as a regulatory nutritional stress response in a competitive two-species biofilm: An individual-based cellular automata model TEJESH REDDY CHIRATHANAMETTU and PARAG D PAWAR* Department of Chemical Engineering, Indian Institute of Technology Hyderabad, Hyderabad, India *Corresponding author (Email, [email protected]) MS received 4 May 2020; accepted 25 August 2020 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. Pseudomonas aeruginosa and Staphylococcus aureus are two prevalent causative pathogens that coexist in biofilm-associated infections. Despite being the slower-growing species, P. aeruginosa 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 P. aeruginosa 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 S. aureus subpopulation. The latter resulted in increased release of autoinducer, and subsequently the upregulation of P. aeruginosa cells via quorum sensing. Upregulated P. aeruginosa cells released HQNO at enhanced rates, thereby inducing phenotypic switching of S. aureus to SCVs which consume nutrient at a reduced rate. This shifted the nutrient distribution back in favor of P. aeruginosa, thereby relieving nutritional stress. Increase in nutritional stress potentiated the transformation of S. aureus into SCVs. HQNO production decreased once nutritional stress was relieved, indicating that phenotypic switching acts as a regulatory stress-adaptive response. Keywords. variant
Cellular automata; nutritional stress; phenotypic switching; polymicrobial biofilms; small colony
1. Introduction It has been well established that bacteria grow preferentially in the biofilm mode of growth wherein microorganisms form self-assembled, surface-associated communities (Hall-Stoodley et al. 2004). Biofilms are associated with recurrent infections that are difficult to treat because of their recalcitrance to antibiotics. In vitro studies assessing growth dynamics and antibiotic tolerance of biofilms have typically been performed with single species (Sena et al. 2006; Ito et al. 2009; Abidi et al. 2013; Duus et al. 2013; Eyoh et al. 2014; Vuotto et al. 2014; Moghadam et al. 2014; Qi et al. http://www.ias.ac.in/jb
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