Adaptive physiological and metabolic alterations in Staphylococcus aureus evolution under vancomycin exposure

Xin Cheng, Yue Shi, Yadong Liu, Yibin Xu, Jingxin Ma, Liyan Ma, Zerui Wang, Shuilong Guo, Jianrong Su
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Abstract

Staphylococcus aureus can develop antibiotic resistance and evade immune responses, causing infections in different body sites. However, the metabolic changes underlying this process are poorly understood. A variant strain, C1V, was derived from the parental strain C1 by exposing it to increasing concentrations of vancomycin in vitro. C1V exhibited a vancomycin-intermediate phenotype and physiological changes compared to C1. It showed higher survival rates than C1 when phagocytosed by Raw264.7 cells. Metabolomics analysis identified significant metabolic differences pre- and post-induction (C1 + SC1 vs. C1V + SC1V: 201 metabolites) as well as pre- and post-phagocytosis (C1 vs. SC1: 50 metabolites; C1V vs. SC1V: 95 metabolites). The variant strain had distinct morphological characteristics, decreased adhesion ability, impaired virulence, and enhanced resistance to phagocytosis compared to the parental strain. Differential metabolites may contribute to S. aureus ‘ resistance to antibiotics and phagocytosis, offering insights into potential strategies for altering vancomycin nonsusceptibility and enhancing phagocyte killing by manipulating bacterial metabolism.

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万古霉素暴露下金黄色葡萄球菌进化过程中的适应性生理和代谢变化
金黄色葡萄球菌可产生抗生素耐药性并逃避免疫反应,从而在人体不同部位造成感染。然而,人们对这一过程背后的新陈代谢变化知之甚少。通过在体外将亲本菌株 C1 暴露于浓度不断升高的万古霉素,衍生出了变异菌株 C1V。与 C1 相比,C1V 表现出万古霉素中度表型和生理变化。当被 Raw264.7 细胞吞噬时,它的存活率高于 C1。代谢组学分析确定了诱导前后(C1 + SC1 vs. C1V + SC1V:201 个代谢物)以及吞噬前后(C1 vs. SC1:50 个代谢物;C1V vs. SC1V:95 个代谢物)的显著代谢差异。与亲本菌株相比,变异菌株具有明显的形态特征,粘附能力下降,毒力减弱,抗吞噬能力增强。不同的代谢物可能会导致金黄色葡萄球菌对抗生素和吞噬细胞的耐药性,这为通过操纵细菌代谢来改变万古霉素不敏感性和增强吞噬细胞杀伤力的潜在策略提供了启示。
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