Zhong Qifeng, Nasreen Marufa, Yang Ruizhe, Struwe Michel, Kobe Bostjan, Kappler Ulrike
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland, Australia.
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia.
J Bacteriol. 2025 May 22;207(5):e0046324. doi: 10.1128/jb.00463-24. Epub 2025 Mar 31.
Sulfoxide reductases in pathogenic bacteria have recently received increasing attention for their association with virulence and survival within the host. Here, we have re-investigated the physiological role of the molybdenum-containing DmsABC dimethyl sulfoxide (DMSO) reductase from , which has a proposed role in anaerobic respiration with DMSO. Our investigation into potential physiological substrates revealed that DmsABC efficiently reduces pyrimidine N-oxide, nicotinamide N-oxide, and methionine sulfoxide, and exposure to host cell-produced stressors such as hypochlorite or hydrogen peroxide specifically increased expression of the gene. strains lacking showed increased lag times in the presence of hypochlorite, and these strains also showed up to a 90% reduction in adherence to human bladder cells. Interestingly, in the presence of hypochlorite, expression of multiple alternative S-/N-oxide reductases present in was elevated by 2- to 4-fold in a ∆ strain compared to the wild-type strain, suggesting functional redundancy. The phenotypes of the ∆ strains were strikingly similar to ∆ strains of the respiratory pathogen , which confirms the role of both enzymes in supporting host-pathogen interactions. We propose that this function is conserved in enzymes closely related to DmsABC. Our study also uncovered that the expression of many Mo enzymes was induced by oxidative stressors, including metals such as copper, and further work should be directed at determining the connection of these enzymes to host-pathogen interactions.IMPORTANCEBacterial urinary tract infections are debilitating and frequently recurring in human populations worldwide, and strains are a major cause of these infections. In this study, we have uncovered a new mechanism by which can avoid being killed by the human immune system. The bacteria use a set of seven related enzymes that can reverse damage to essential cell components such as amino acids, vitamins, and DNA building blocks. Antibacterial compounds produced by the human immune system specifically induced the production of these enzymes, confirming that they play a role in helping survive during infection and making these enzymes potential future drug targets.
致病细菌中的亚砜还原酶最近因其与宿主内毒力和生存的关联而受到越来越多的关注。在此，我们重新研究了来自[具体细菌名称未给出]的含钼DmsABC二甲基亚砜（DMSO）还原酶的生理作用，该酶在以DMSO进行厌氧呼吸中具有推测作用。我们对潜在生理底物的研究表明，DmsABC能有效还原嘧啶N - 氧化物、烟酰胺N - 氧化物和甲硫氨酸亚砜，并且暴露于宿主细胞产生的应激源（如次氯酸盐或过氧化氢）会特异性增加[具体基因名称未给出]基因的表达。缺乏[具体基因名称未给出]的[细菌名称未给出]菌株在次氯酸盐存在下显示出延长的滞后期，并且这些菌株对人膀胱细胞的黏附也减少了高达90%。有趣的是，在次氯酸盐存在下，与野生型菌株相比，[细菌名称未给出]中存在的多种替代S - /N - 氧化物还原酶在∆[具体基因名称未给出]菌株中的表达升高了2至4倍，表明功能冗余。[细菌名称未给出] ∆[具体基因名称未给出]菌株的表型与呼吸道病原体[具体细菌名称未给出]的∆[具体基因名称未给出]菌株惊人地相似，这证实了这两种酶在支持宿主 - 病原体相互作用中的作用。我们提出这种功能在与DmsABC密切相关的酶中是保守的。我们的研究还发现许多[细菌名称未给出]钼酶的表达受氧化应激源诱导，包括铜等金属，进一步的工作应致力于确定这些酶与宿主 - 病原体相互作用的联系。
重要性
细菌性尿路感染使人衰弱且在全球人群中频繁复发，[细菌名称未给出]菌株是这些感染的主要原因。在这项研究中，我们发现了[细菌名称未给出]避免被人类免疫系统杀死的一种新机制。该细菌使用一组七种相关酶，这些酶可以逆转对必需细胞成分（如氨基酸、维生素和DNA构建块）的损伤。人类免疫系统产生的抗菌化合物特异性诱导了这些酶的产生，证实它们在帮助[细菌名称未给出]在感染期间存活中发挥作用，并使这些酶成为未来潜在的药物靶点。
