Joo Hwang-Soo, Chatterjee Som S, Villaruz Amer E, Dickey Seth W, Tan Vee Y, Chen Yan, Sturdevant Daniel E, Ricklefs Stacy M, Otto Michael
Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Genomics Unit, Research Technology Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
mBio. 2016 Oct 25;7(5):e01579-16. doi: 10.1128/mBio.01579-16.
The virulence of many bacterial pathogens, including the important human pathogen Staphylococcus aureus, depends on the secretion of frequently large amounts of toxins. Toxin production involves the need for the bacteria to make physiological adjustments for energy conservation. While toxins are primarily targets of gene regulation, such changes may be accomplished by regulatory functions of the toxins themselves. However, mechanisms by which toxins regulate gene expression have remained poorly understood. We show here that the staphylococcal phenol-soluble modulin (PSM) toxins have gene regulatory functions that, in particular, include inducing expression of their own transport system by direct interference with a GntR-type repressor protein. This capacity was most pronounced in PSMs with low cytolytic capacity, demonstrating functional specification among closely related members of that toxin family during evolution. Our study presents a molecular mechanism of gene regulation by a bacterial toxin that adapts bacterial physiology to enhanced toxin production.
Toxins play a major role in many bacterial diseases. When toxins are produced during infection, the bacteria need to balance this energy-consuming task with other physiological processes. However, it has remained poorly understood how toxins can impact gene expression to trigger such adaptations. We found that specific members of a toxin family in the major human pathogen Staphylococcus aureus have evolved for gene regulatory purposes. These specific toxins interact with a DNA-binding regulator protein to enable production of the toxin export machinery and ascertain that the machinery is not expressed when toxins are not made and it is not needed. Our study gives mechanistic insight into how toxins may directly adjust bacterial physiology to times of toxin production during infection.
许多细菌病原体的毒力，包括重要的人类病原体金黄色葡萄球菌，都依赖于大量毒素的分泌。毒素产生涉及细菌为节约能量而进行生理调节的需求。虽然毒素主要是基因调控的靶点，但这种变化可能通过毒素自身的调控功能来实现。然而，毒素调节基因表达的机制仍知之甚少。我们在此表明，葡萄球菌酚溶性调节蛋白（PSM）毒素具有基因调控功能，特别是通过直接干扰一种GntR型阻遏蛋白来诱导其自身转运系统的表达。这种能力在细胞溶解能力较低的PSM中最为明显，表明该毒素家族在进化过程中密切相关成员之间存在功能特异性。我们的研究提出了一种细菌毒素调节基因的分子机制，该机制使细菌生理适应增强的毒素产生。
毒素在许多细菌疾病中起主要作用。当在感染过程中产生毒素时，细菌需要在这项耗能任务与其他生理过程之间取得平衡。然而，毒素如何影响基因表达以引发这种适应性变化仍知之甚少。我们发现，主要人类病原体金黄色葡萄球菌中毒素家族的特定成员已经进化出基因调控功能。这些特定毒素与一种DNA结合调节蛋白相互作用，以启动毒素输出机制的产生，并确保在不产生毒素且不需要该机制时不表达该机制。我们的研究为毒素如何在感染期间直接将细菌生理调节到毒素产生时期提供了机制上的见解。
