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

Abstract

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 metabolically-challenged 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 stressadaptive response.

Strain-specific interspecies interactions between co-isolated pairs of Staphylococcus aureus and Pseudomonas aeruginosa from patients with tracheobronchitis or bronchial colonization

“…Surfactant peptides secreted by S. aureus in a QS-controlled fashion have been associated with biofilm detachment and consequent bacterial dissemination 23 . On the other hand, among the variety of QS signaling molecules in P. aeruginosa , quinolone-based signals, with 2-heptyl-3-hydroxy-4-quilonone (PQS) as the main effector molecule, seem to induce the production of virulence factors in the presence of Gram-positive organisms, such as S. aureus 17 , 21 , 24 . Two other QS systems in P. aeruginosa (LasR and RhIR) work regulating PQS through its main effector molecule, N-acylhomoserine lactone (AHL) 1 .…”

Bacterial Interactions in the Context of Chronic Wound Biofilm: A Review

“…In addition, the presence of anaerobes was related to ulcer depth [ 52 ] and to poor prognosis [ 35 ]. Finally, the spatial organization of the coexisting species in wounds was influenced by nutrient availability [ 54 , 55 ], compounds such as dioxygen (anoxic at the wound center or within the biofilm [ 56 ] and hypoxic at the edge [ 57 , 58 ]), and biofilm structures [ 59 , 60 ] ( Figure 1 ). The inter-relationships between the different species present in the wound affect their microbiogeography either by competing [ 61 ], repelling [ 62 ], cheating [ 63 , 64 ], and/or attracting [ 65 ] each other.…”

Multispecies biofilms in fermentation: Biofilm formation, microbial interactions, and communication

“…In dual-species biofilms formed by foodborne pathogens, there was competition for nutrients between the two species, P. aeruginosa and S. aureus. A rapid increase in the proportion of S. aureus resulted in an increased release of the autoinducer, which enhanced the release of 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) by P. aeruginosa, and HQNO induced the switch of S. aureus to the slower-growing phenotype, thereby relieving nutritional stress (Chirathanamettu & Pawar, 2020). In biofilms, the mass-transfer performance in the microenvironment and the spatial distribution of cells can affect QS systems.…”