Anderson Mark T, Mitchell Lindsay A, Sintsova Anna, Rice Katherine A, Mobley Harry L T
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
mSystems. 2019 Aug 6;4(4):e00285-19. doi: 10.1128/mSystems.00285-19.
Sulfur is an essential nutrient that contributes to cellular redox homeostasis, transcriptional regulation, and translation initiation when incorporated into different biomolecules. Transport and reduction of extracellular sulfate followed by cysteine biosynthesis is a major pathway of bacterial sulfur assimilation. For the opportunistic pathogen , function of the cysteine biosynthesis pathway is required for extracellular phospholipase activity and flagellum-mediated surface motility, but little else is known about the influence of sulfur assimilation on the physiology of this organism. In this work, it was determined that an cysteine auxotroph fails to differentiate into hyperflagellated and elongated swarmer cells and that cysteine, but not other organic sulfur molecules, restores swarming motility to these bacteria. The cysteine auxotroph further exhibits reduced transcription of phospholipase, hemolysin, and flagellin genes, each of which is subject to transcriptional control by the flagellar regulatory system. Based on these data and the central role of cysteine in sulfur assimilation, it was reasoned that environmental sulfur availability may contribute to the regulation of these functions in Indeed, bacteria that are starved for sulfate exhibit substantially reduced transcription of the genes for hemolysin, phospholipase, and the FlhD flagellar master regulator. A global transcriptomic analysis further defined a large set of genes that are responsive to extracellular sulfate availability, including genes that encode membrane transport, nutrient utilization, and metabolism functions. Finally, sulfate availability was demonstrated to alter cytolytic activity, suggesting that sulfate assimilation may impact the virulence of this organism. is a versatile bacterial species that inhabits diverse environmental niches and is capable of pathogenic interactions with host organisms ranging from insects to humans. This report demonstrates for the first time the extensive impacts that environmental sulfate availability and cysteine biosynthesis have on the transcriptome of The finding that greater than 1,000 genes are differentially expressed depending on sulfate availability suggests that sulfur abundance is a crucial factor that controls the physiology of this organism. Furthermore, the high relative expression levels for the putative virulence factors flagella, phospholipase, and hemolysin in the presence of sulfate suggests that a sulfur-rich host environment could contribute to the transcription of these genes during infection.
硫是一种必需营养素，当它被整合到不同生物分子中时，有助于细胞氧化还原稳态、转录调控和翻译起始。细胞外硫酸盐的转运和还原，随后进行半胱氨酸生物合成，是细菌硫同化的主要途径。对于这种机会致病菌而言，半胱氨酸生物合成途径的功能对于细胞外磷脂酶活性和鞭毛介导的表面运动是必需的，但关于硫同化对该生物体生理的影响，人们所知甚少。在这项研究中，确定了一种半胱氨酸营养缺陷型菌株无法分化为超鞭毛化和伸长的群体游动细胞，并且半胱氨酸而非其他有机硫分子可恢复这些细菌的群体游动能力。该半胱氨酸营养缺陷型菌株还进一步表现出磷脂酶、溶血素和鞭毛蛋白基因的转录减少，这些基因均受鞭毛调节系统的转录控制。基于这些数据以及半胱氨酸在硫同化中的核心作用，可以推断环境中的硫可用性可能有助于对该菌中这些功能的调节。确实，缺乏硫酸盐的细菌表现出溶血素、磷脂酶和鞭毛主调节因子FlhD基因的转录大幅减少。一项全转录组分析进一步确定了大量对细胞外硫酸盐可用性有反应的该菌基因，包括编码膜转运、营养利用和代谢功能的基因。最后，证明了硫酸盐可用性会改变该菌的溶细胞活性，表明硫酸盐同化可能影响该生物体的毒力。该菌是一种适应性很强的细菌物种，栖息于多种环境生态位，能够与从昆虫到人类的宿主生物体发生致病相互作用。本报告首次证明了环境硫酸盐可用性和半胱氨酸生物合成对该菌转录组的广泛影响。根据硫酸盐可用性，超过1000个该菌基因差异表达这一发现表明，硫的丰度是控制该生物体生理的关键因素。此外，在有硫酸盐存在的情况下，假定的毒力因子鞭毛、磷脂酶和溶血素的相对表达水平较高，这表明富含硫的宿主环境可能在感染期间促进这些基因的转录。
