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 stress-adaptive response.

中文翻译：

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群体感应诱导的表型转换作为竞争性两种生物膜中的调节性营养应激反应：基于个体的细胞自动机模型

多微生物生物膜中营养物质的竞争可能导致易感物种受到营养压力。细菌生长率和种间相互作用对其易感性和对营养压力的反应的影响尚不清楚。铜绿假单胞菌和金黄色葡萄球菌是两种常见的致病病原体，它们共存于生物膜相关感染中。尽管是生长缓慢的物种，铜绿假单胞菌通过释放 2-heptyl-4-hydroxyquinoline N-诱导金黄色葡萄球菌表型转换为代谢挑战的小菌落变体 (SCV)，在两种生物膜中占主导地位。氧化物 (HQNO)。我们假设铜绿假单胞菌在与金黄色葡萄球菌的竞争中经历营养应激，并且 HQNO 的释放是对营养应激的适应性反应。我们提出了一个基于个体的两个物种生物膜模型，其中实体之间的相互作用会诱发紧急特性。随着生物膜的成熟，这两个物种的生长速度差异导致营养物质分布不均匀，从而导致铜绿假单胞菌的营养压力和金黄色葡萄球菌亚群比例同时增加。后者导致自诱导剂释放增加，随后通过群体感应上调铜绿假单胞菌细胞。上调的铜绿假单胞菌细胞以更高的速率释放 HQNO，从而诱导金黄色葡萄球菌的表型转换为以降低的速率消耗营养的 SCV。这使营养分布重新有利于铜绿假单胞菌，从而缓解营养压力。营养压力的增加促进了金黄色葡萄球菌的转化。金黄色葡萄球菌转化为 SCV。一旦营养压力得到缓解，HQNO 的产生就会减少，这表明表型转换是一种调节性压力适应反应。