Li Jing, Chen Xiaojie, Lin Jiafu, Yuan Yang, Huang Ting, Du Lianming, Prithiviraj Balakrishnan, Zhang Aixue, Wang Xinrong, Chu Yiwen, Zhao Kelei
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu, Sichuan, China.
School of Mathematical Sciences, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Environ Microbiol. 2021 Dec;23(12):7432-7444. doi: 10.1111/1462-2920.15461. Epub 2021 Mar 24.
Interspecific interaction happens frequently among bacterial species and can promote the colonization of polymicrobial community in various environments. However, it is not clear whether the intervention of antibiotics, which is a common therapeutic method for infectious disease, will influence the interacting dynamics of different pathogenic bacteria. By using the frequently co-isolated bacteria Pseudomonas aeruginosa and Staphylococcus aureus as models, here we identify an antibiotic-determined mutual invasion relationship between bacterial pathogens. We show that although P. aeruginosa has a significant intrinsic competitive advantage over S. aureus by producing the quorum-sensing (QS)-controlled anti-staphylococcal molecules, methicillin-resistant S. aureus (MRSA) can inhibit neighbouring P. aeruginosa in the presence of subinhibitory aminoglycoside antibiotics (e.g. streptomycin) to P. aeruginosa. Importantly, subinhibitory streptomycin decreases the expression of QS-regulated genes in P. aeruginosa and thus relieves the survival stress of MRSA brought by P. aeruginosa. On the other side, the iron-uptake systems and pathogenicity of MRSA can be enhanced by the extracellular products of streptomycin-treated P. aeruginosa. Therefore, this study provides an explanation for the substitution of dominant species and persistent coexistence of bacterial pathogens in the host with repeated antibiotic therapies and contributes to further understanding the pathogenesis of chronic polymicrobial infections.
种间相互作用在细菌物种之间频繁发生，并可促进多微生物群落定殖于各种环境中。然而，作为传染病常见治疗方法的抗生素干预是否会影响不同病原菌的相互作用动态尚不清楚。通过使用经常共同分离出的细菌铜绿假单胞菌和金黄色葡萄球菌作为模型，我们在此确定了病原菌之间由抗生素决定的相互入侵关系。我们表明，尽管铜绿假单胞菌通过产生群体感应（QS）控制的抗葡萄球菌分子而比金黄色葡萄球菌具有显著的内在竞争优势，但耐甲氧西林金黄色葡萄球菌（MRSA）在存在对铜绿假单胞菌有亚抑菌作用的氨基糖苷类抗生素（如链霉素）时，可以抑制邻近的铜绿假单胞菌。重要的是，亚抑菌浓度的链霉素会降低铜绿假单胞菌中QS调控基因的表达，从而减轻铜绿假单胞菌给MRSA带来的生存压力。另一方面，经链霉素处理的铜绿假单胞菌的胞外产物可增强MRSA的铁摄取系统和致病性。因此，本研究为宿主中病原菌优势种替代和长期共存以及反复使用抗生素治疗提供了解释，并有助于进一步理解慢性多微生物感染的发病机制。
