Department of Microbiology, Immunology and Pathology, Mycobacteria Research Laboratories, Colorado State University , Fort Collins, Colorado, USA.
Department of Medicine, Molecular Immunity Unit, University of Cambridge, MRC-Laboratory of Molecular Biology , Cambridge, United Kingdom.
Microbiol Spectr. 2023 Dec 12;11(6):e0158823. doi: 10.1128/spectrum.01588-23. Epub 2023 Oct 24.
Difficult-to-treat pulmonary infections caused by nontuberculous mycobacteria of the group have been steadily increasing in the USA and globally. Owing to the relatively recent recognition of as a human pathogen, basic and translational research to address critical gaps in diagnosis, treatment, and prevention of diseases caused by this microorganism has been lagging behind that of the better-known mycobacterial pathogen, . To begin unraveling the molecular mechanisms of pathogenicity of , we here focus on the study of a two-component regulator known as PhoPR which we found to be under strong evolutionary pressure during human lung infection. We show that PhoPR is activated at acidic pH and serves to regulate a defined set of genes involved in host adaptation. Accordingly, clinical isolates from chronically infected human lungs tend to hyperactivate this regulator enabling to escape macrophage killing.
在美国和全球范围内，由非结核分枝杆菌引起的难治性肺部感染一直在稳步增加。由于 最近才被确认为人类病原体，因此针对该微生物引起的疾病在诊断、治疗和预防方面的关键空白的基础和转化研究一直落后于更为人熟知的分枝杆菌病原体 。为了开始揭示 的致病分子机制，我们在这里重点研究一种称为 PhoPR 的双组分调节剂，我们发现该调节剂在人类肺部感染期间受到强烈的进化压力。我们表明 PhoPR 在酸性 pH 值下被激活，并用于调节与宿主适应相关的一组特定基因。因此，来自慢性感染人类肺部的临床分离株往往会过度激活这种调节剂，从而使 逃避巨噬细胞杀伤。
