Bacterial fight-and-flight responses enhance virulence in a polymicrobial infection
Bacterial fight-and-flight responses enhance virulence in a polymicrobial infection
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DOI：
10.1073/pnas.1400586111
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发表时间：
2014-05-27
影响因子：
11.1
通讯作者：
Whiteley, Marvin
中科院分区：
文献类型：
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作者：
Stacy, Apollo;Everett, Jake;Whiteley, Marvin
口腔病原体伴放线菌聚集杆菌（Aggregatibacteractinomycetemcomitans，Aa）存在于具有许多微生物的感染部位，包括链球菌（Streptococcus gordonii，Sg）等口腔链球菌。在感染过程中，Sg通过产生其优选的碳源L-乳酸盐来促进Aa的毒力，这种现象被称为交叉喂养。然而，与许多链球菌一样，Sg也产生高水平的抗微生物过氧化氢（H2 O2），导致Aa在合并感染期间如何处理这种有效的抗微生物剂的问题。在这里，我们表明，Aa具有两个互补的反应H2 O2：解毒或战斗的反应介导的过氧化氢酶（KatA）和分散或飞行反应介导的分散蛋白B（Dsp B），一种酶，溶解Aa生物膜。使用小鼠脓肿感染模型，我们表明，这两个反应所需的Sg促进Aa毒力。虽然KatA的作用是解毒H2 O2在共同感染，混合感染的三维空间分析显示，DspB是Aa所需的空间组织本身在一个最佳的距离（>4 μ m）从Sg，我们建议允许交叉喂养，但减少暴露于抑制水平的H2 O2。此外，这些行为不仅有利于Aa，也有利于Sg，这表明战斗和逃跑刺激了社区的适应性。这些结果表明，由人类肠道细菌产生的抗微生物剂通过调节病原菌在感染部位的空间位置来增强病原菌的毒力。
The oral pathogen Aggregatibacter actinomycetemcomitans (Aa) resides in infection sites with many microbes, including commensal streptococci such as Streptococcus gordonii (Sg). During infection, Sg promotes the virulence of Aa by producing its preferred carbon source, L-lactate, a phenomenon referred to as cross-feeding. However, as with many streptococci, Sg also produces high levels of the antimicrobial hydrogen peroxide (H2O2), leading to the question of how Aa deals with this potent antimicrobial during coinfection. Here, we show that Aa possesses two complementary responses to H2O2: a detoxification or fight response mediated by catalase (KatA) and a dispersion or flight response mediated by Dispersin B (DspB), an enzyme that dissolves Aa biofilms. Using a murine abscess infection model, we show that both of these responses are required for Sg to promote Aa virulence. Although the role of KatA is to detoxify H2O2 during coinfection, 3D spatial analysis of mixed infections revealed that DspB is required for Aa to spatially organize itself at an optimal distance (>4 mu m) from Sg, which we propose allows cross-feeding but reduces exposure to inhibitory levels of H2O2. In addition, these behaviors benefit not only Aa but also Sg, suggesting that fight and flight stimulate the fitness of the community. These results reveal that an antimicrobial produced by a human commensal bacterium enhances the virulence of a pathogenic bacterium by modulating its spatial location in the infection site.