Commensal bacteria augment Staphylococcus aureus infection by inactivation of phagocyte-derived reactive oxygen species.
Commensal bacteria augment Staphylococcus aureus infection by inactivation of phagocyte-derived reactive oxygen species.
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共生菌通过灭活吞噬细胞衍生的活性氧增强金黄色葡萄球菌感染。
DOI：
10.1371/journal.ppat.1009880
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发表时间：
2021-09
期刊：
影响因子：
6.7
通讯作者：
Foster SJ
中科院分区：
文献类型：
--
作者：
Gibson JF;Pidwill GR;Carnell OT;Surewaard BGJ;Shamarina D;Sutton JAF;Jeffery C;Derré-Bobillot A;Archambaud C;Siggins MK;Pollitt EJG;Johnston SA;Serror P;Sriskandan S;Renshaw SA;Foster SJ
金黄色葡萄球菌是一种人体内的机会致病菌，可引起潜在的致命性疾病。非致病性微生物菌群或其组分的存在，在感染点，显着增加S。金黄色葡萄球菌的致病性，这一过程被称为增强。增强与巨噬细胞相互作用有关，但机制未知。在这里，我们证明了广泛的跨王国微生物可以增加S。金黄色葡萄球菌疾病和粪肠球菌发病机理也可以被增强。共同施用增强材料也形成了有效的S.金黄色。在体外，增强材料保护S。金黄色葡萄球菌直接从活性氧（ROS），这与体内研究相关，其中增强恢复了对ROS敏感的减毒突变体katA ahpC的完全毒力。在细胞水平，增强通过改善ROS增加巨噬细胞内的细菌存活，导致增殖和逃逸。我们已经定义了增强的分子基础，这代表了感染启动的一个重要方面。S.金黄色葡萄球菌是人类皮肤和鼻孔的寄生虫。然而，如果它能够突破我们的保护屏障，如皮肤，通常通过伤口或手术，它可能会导致严重的疾病。如果感染是通过伤口发生的，这种初始接种物既包含病原体，也包含微生物区系的其他成员，还包含更广泛的环境微生物。我们先前描述了“增强”，即这种其他非致病性物质可以增强S。金黄色葡萄球菌导致严重的疾病结果。在这里，我们已经确定了扩大材料的广度，并阐明了其活动的细胞和分子基础。增强作用是通过S的屏蔽而发生的。巨噬细胞产生的活性氧簇的直接杀菌作用对金黄色葡萄球菌产生影响。这种初始保护使S.金黄色葡萄球菌感染。理解增强不仅解释了S相互作用的一个重要方面。金黄色葡萄球菌与我们的先天免疫系统，而且还提供了一个平台，为开发新的预防方法。
Staphylococcus aureus is a human commensal organism and opportunist pathogen, causing potentially fatal disease. The presence of non-pathogenic microflora or their components, at the point of infection, dramatically increases S. aureus pathogenicity, a process termed augmentation. Augmentation is associated with macrophage interaction but by a hitherto unknown mechanism. Here, we demonstrate a breadth of cross-kingdom microorganisms can augment S. aureus disease and that pathogenesis of Enterococcus faecalis can also be augmented. Co-administration of augmenting material also forms an efficacious vaccine model for S. aureus. In vitro, augmenting material protects S. aureus directly from reactive oxygen species (ROS), which correlates with in vivo studies where augmentation restores full virulence to the ROS-susceptible, attenuated mutant katA ahpC. At the cellular level, augmentation increases bacterial survival within macrophages via amelioration of ROS, leading to proliferation and escape. We have defined the molecular basis for augmentation that represents an important aspect of the initiation of infection. S. aureus is a commensal inhabitant of the human skin and nares. However, it can cause serious diseases if it is able to breach our protective barriers such as the skin, often via wounds or surgery. If infection occurs via a wound, this initial inoculum contains both the pathogen, other members of the microflora and also wider environmental microbes. We have previously described “augmentation”, whereby this other non-pathogenic material can enhance the ability of S. aureus to lead to a serious disease outcome. Here we have determined the breadth of augmenting material and elucidated the cellular and molecular basis for its activity. Augmentation occurs via shielding of S. aureus from the direct bactericidal effects of reactive oxygen species produced by macrophages. This initial protection enables the effective establishment of S. aureus infection. Understanding augmentation not only explains an important facet of the interaction of S. aureus with our innate immune system, but also provides a platform for the development of novel prophylaxis approaches.
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影响因子：
9.8
作者：
Grant AJ;Restif O;McKinley TJ;Sheppard M;Maskell DJ;Mastroeni P
通讯作者：
Mastroeni P
影响因子：
3.7
作者：
Hoffmann C;Dollive S;Grunberg S;Chen J;Li H;Wu GD;Lewis JD;Bushman FD
通讯作者：
Bushman FD
影响因子：
6.4
作者：
Dockrell, DH;Lee, M;Read, RC
通讯作者：
Read, RC
影响因子：
7.7
作者：
Lund VA;Wacnik K;Turner RD;Cotterell BE;Walther CG;Fenn SJ;Grein F;Wollman AJ;Leake MC;Olivier N;Cadby A;Mesnage S;Jones S;Foster SJ
通讯作者：
Foster SJ
影响因子：
28.3
作者：
Ercoli G;Fernandes VE;Chung WY;Wanford JJ;Thomson S;Bayliss CD;Straatman K;Crocker PR;Dennison A;Martinez-Pomares L;Andrew PW;Moxon ER;Oggioni MR
通讯作者：
Oggioni MR