Department of Oncology, The First Affiliated Hospital, University of Science and Technology of China, Hefei, People's Republic of China.
Department of Life Science and Medicine, University of Science and Technology of China, Hefei, People's Republic of China.
Microbiol Spectr. 2023 Jun 15;11(3):e0359622. doi: 10.1128/spectrum.03596-22. Epub 2023 May 18.
Staphylococcus aureus is a pathogenic bacterium with a widespread distribution that can cause diverse severe diseases. The membrane-bound nitrate reductase NarGHJI serves respiratory function. However, little is known about its contribution to virulence. In this study, we demonstrated that disruption results in the downregulation of virulence genes (e.g., , , , , and ) and reduces the hemolytic activity of the methicillin-resistant S. aureus (MRSA) strain USA300 LAC. Moreover, we provided evidence that NarGHJI participates in regulating host inflammatory response. A mouse model of subcutaneous abscess and Galleria mellonella survival assay demonstrated that the mutant was significantly less virulent than the wild type. Interestingly, NarGHJI contributes to virulence in an -dependent manner, and the role of NarGHJI differs between different S. aureus strains. Our study highlights the novel role of NarGHJI in regulating virulence, thereby providing a new theoretical reference for the prevention and control of S. aureus infection. Staphylococcus aureus is a notorious pathogen that poses a great threat to human health. The emergence of drug-resistant strains has significantly increased the difficulty of preventing and treating S. aureus infection and enhanced the pathogenic ability of the bacterium. This indicates the importance of identifying novel pathogenic factors and revealing the regulatory mechanisms through which they regulate virulence. The nitrate reductase NarGHJI is mainly involved in bacterial respiration and denitrification, which can enhance bacterial survival. We demonstrated that disruption results in the downregulation of the system and -dependent virulence genes, suggesting that NarGHJI participates in the regulation of S. aureus virulence in an -dependent manner. Moreover, the regulatory approach is strain specific. This study provides a new theoretical reference for the prevention and control of S. aureus infection and reveals new targets for the development of therapeutic drugs.
金黄色葡萄球菌是一种分布广泛的致病菌，可以引起多种严重疾病。膜结合型硝酸盐还原酶 NarGHJI 具有呼吸功能。然而，其对毒力的贡献知之甚少。在这项研究中，我们证明了破坏导致毒力基因（例如， ， ， ， 和 ）下调，并降低耐甲氧西林金黄色葡萄球菌（MRSA）菌株 USA300 LAC 的溶血活性。此外，我们提供了证据表明 NarGHJI 参与调节宿主炎症反应。皮下脓肿小鼠模型和大蜡螟存活试验表明， 突变体比野生型的毒力显著降低。有趣的是，NarGHJI 以 - 依赖的方式有助于毒力，并且 NarGHJI 在不同金黄色葡萄球菌菌株中的作用不同。我们的研究强调了 NarGHJI 在调节毒力方面的新作用，为金黄色葡萄球菌感染的预防和控制提供了新的理论参考。金黄色葡萄球菌是一种臭名昭著的病原体，对人类健康构成巨大威胁。耐药菌株的出现极大地增加了预防和治疗金黄色葡萄球菌感染的难度，并增强了细菌的致病性。这表明确定新的致病因素和揭示它们调节毒力的调节机制非常重要。硝酸盐还原酶 NarGHJI 主要参与细菌呼吸和反硝化作用，从而增强细菌的生存能力。我们证明了破坏导致 系统和 - 依赖的毒力基因下调，表明 NarGHJI 以 - 依赖的方式参与金黄色葡萄球菌毒力的调节。此外，调节方式是菌株特异性的。这项研究为金黄色葡萄球菌感染的预防和控制提供了新的理论参考，并为治疗药物的开发揭示了新的靶标。
