Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.
Front Cell Infect Microbiol. 2022 May 10;12:817336. doi: 10.3389/fcimb.2022.817336. eCollection 2022.
Chronic infections in the cystic fibrosis (CF) airway are composed of both pathogenic and commensal bacteria. However, chronic infections are the leading cause of lung deterioration in individuals with CF. Interestingly, oral commensals can translocate to the CF lung and their presence is associated with improved lung function, presumably due to their ability to antagonize . We have previously shown that one commensal, , produces hydrogen peroxide that reacts with nitrite to generate reactive nitrogen intermediates (RNI) which inhibit growth. In this study, we sought to understand the global impact of commensal-mediated RNI on the transcriptome. RNA sequencing analysis revealed that and nitrite-mediated RNI dysregulated expression of denitrification genes in a CF isolate of compared to when this isolate was only exposed to . Further, loss of a nitric oxide reductase subunit () rendered an acute isolate more susceptible to mediated RNI. Additionally, -mediated RNI inactivated aconitase activity. Lastly, we report that isolates recovered from CF individuals are uniquely hypersensitive to -mediated RNI compared to acute infection or environmental isolates. These findings illustrate that hinders the ability of to respond to RNI, which potentially prevents CF isolates from resisting commensal and host-induced RNI in the CF airway.
囊性纤维化 (CF) 气道中的慢性感染由致病细菌和共生菌组成。然而，慢性感染是 CF 患者肺部恶化的主要原因。有趣的是，口腔共生菌可以转移到 CF 肺部，它们的存在与肺功能的改善有关，这可能是由于它们抑制的能力。我们之前已经表明，一种共生菌 产生的过氧化氢与亚硝酸盐反应生成活性氮中间体 (RNI)，抑制的生长。在这项研究中，我们试图了解共生菌介导的 RNI 对 转录组的全局影响。RNA 测序分析显示，与仅暴露于 的 CF 分离株相比， 和亚硝酸盐介导的 RNI 使硝酸盐还原酶亚基 () 缺失的急性 分离株中硝酸盐还原基因的表达失调。此外，介导的 RNI 使急性 分离株的 aconitase 活性失活。最后，我们报告说，与急性感染或环境 分离株相比，从 CF 个体中恢复的 分离株对 介导的 RNI 表现出独特的超敏反应。这些发现表明， 阻碍了 对 RNI 的反应能力，这可能阻止 CF 分离株在 CF 气道中抵抗共生菌和宿主诱导的 RNI。
