L. pneumophila resists its self-harming metabolite HGA via secreted factors and collective peroxide scavenging.
L. pneumophila resists its self-harming metabolite HGA via secreted factors and collective peroxide scavenging.
复制标题
作者：
许多致病菌，包括嗜肺军团菌，从环境宿主感染人类。为了在这些水库中生存，细菌必须承受微生物对微生物的竞争。我们以前发现L.嗜肺菌可以通过称为尿黑酸（HGA）的抗菌代谢物与邻近细菌竞争。奇怪的是，L。分泌HGA的嗜肺菌菌株对其作用并不完全免疫：低密度的细菌被HGA强烈抑制，而高密度的细胞是耐受的。这些细菌如何耐受HGA并在细菌间竞争中避免自我伤害？在这里，我们发现HGA毒性通过产生有毒的氢过氧化物而发生，多种因素促进了高密度耐受性。首先，HGA仅在氧化>1小时后才变得完全有毒。虽然这表现为在良好混合的液体培养物中的杀伤延迟，但在生物膜环境中，这可以为HGA在变得有毒之前扩散出去提供时间。其次，HGA产生大量的氢过氧化物，这些氢过氧化物可以被高密度细胞而不是低密度细胞共同清除。第三，高密度细胞产生一种或多种对HGA具有瞬时保护作用的分泌因子。结合起来，我们建议细菌能够部署HGA以在其自身生物膜周围产生活性氧物质，同时保持其内部的无毒条件。总的来说，这些发现有助于解释毒性分子如何广泛地用作细菌间的武器。他们还提供了一些见解，为什么我们目前的一些去污方法，以控制L。嗜肺菌是无效的，导致复发性疾病爆发。在环境条件致病菌感染人类之前，它们必须首先成功地生长并与自然界中的其他微生物竞争，通常是通过分泌的抗菌剂。我们以前发现，细菌嗜肺军团菌，退伍军人病的病原体，可以通过分泌的分子称为HGA与其他微生物竞争。奇怪的是，L。产生HGA的嗜肺菌菌株并不完全对其毒性免疫，这使得这些细菌如何在细菌间战斗期间经受住潜在自靶向抗菌剂的“友好火力”成为一个谜。在这里，我们确定了几种策略，使高密度的细菌种群分泌HGA耐受其影响。我们的研究阐明了HGA是如何工作的。它还指出了一些解释，为什么很难消毒L。从建筑环境中去除嗜肺菌并防止疾病爆发。
Many pathogenic bacteria, including Legionella pneumophila, infect humans from environmental reservoirs. To survive in these reservoirs, bacteria must withstand microbe-on-microbe competition. We previously discovered that L. pneumophila can compete with neighboring bacteria via an antimicrobial metabolite called homogentisic acid (HGA). Curiously, L. pneumophila strains that secrete HGA are not wholly immune to its effects: low-density bacteria are strongly inhibited by HGA, whereas high-density cells are tolerant. How do these bacteria tolerate HGA and avoid self-harm during interbacterial competition? Here, we find that HGA toxicity occurs via the production of toxic hydroperoxides, and multiple factors facilitate high-density tolerance. First, HGA becomes fully toxic only after >1 h of oxidation. While this manifests as a delay in killing within well-mixed liquid cultures, in a biofilm environment, this could provide time for HGA to diffuse away before becoming toxic. Second, HGA generates quantities of hydroperoxides that can be collectively scavenged by high-density, but not low-density, cells. Third, high-density cells produce one or more secreted factors that are transiently protective from HGA. In combination, we propose that the bacteria are able to deploy HGA to generate a pool of reactive oxygen species surrounding their own biofilms while maintaining non-toxic conditions within them. Overall, these findings help to explain how broadly toxic molecules can be used as inter-bacterial weapons. They also provide insights about why some of our current decontamination methods to control L. pneumophila are ineffective, leading to recurrent disease outbreaks. Before environmental opportunistic pathogens can infect humans, they must first successfully grow and compete with other microbes in nature, often via secreted antimicrobials. We previously discovered that the bacterium Legionella pneumophila, the causative agent of Legionnaires’ disease, can compete with other microbes via a secreted molecule called HGA. Curiously, L. pneumophila strains that produce HGA is not wholly immune to its toxicity, making it a mystery how these bacteria can withstand the “friendly fire” of potentially self-targeting antimicrobials during inter-bacterial battles. Here, we identify several strategies that allow the high-density bacterial populations that secrete HGA to tolerate its effects. Our study clarifies how HGA works. It also points to some explanations of why it is difficult to disinfect L. pneumophila from the built environment and prevent disease outbreaks.
登录
查看更多内容
影响因子：
6.4
作者：
Abisado RG;Benomar S;Klaus JR;Dandekar AA;Chandler JR
通讯作者：
Chandler JR
DOI：
10.1073/pnas.1219446110
发表时间：
2013-03-26
影响因子：
11.1
作者：
Ji, Quanjiang;Zhang, Liang;He, Chuan
通讯作者：
He, Chuan
影响因子：
9.4
作者：
Hacek, DM;Dressel, DC;Peterson, LR
通讯作者：
Peterson, LR
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
2.6
作者：
HEBERT, GA;STEIGERWALT, AG;BRENNER, DJ
通讯作者：
BRENNER, DJ