Department of Biomedical Research, Center for Genes, Environment and Health, and.
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado.
Am J Respir Cell Mol Biol. 2020 Mar;62(3):354-363. doi: 10.1165/rcmb.2018-0278OC.
Comparisons of infectivity among the clinically important nontuberculous mycobacteria (NTM) species have not been explored in great depth. Rapid-growing mycobacteria, including and , can cause indolent but progressive lung disease. Slow-growing members of the complex are the most common group of NTM to cause lung disease, and molecular approaches can now distinguish between several distinct species of complex including , , , and . Differential infectivity among these NTM species may, in part, account for differences in clinical outcomes and response to treatment; thus, knowing the relative infectivity of particular isolates could increase prognostication accuracy and enhance personalized treatment. Using human macrophages, we investigated the infectivity and virulence of nine NTM species, as well as multiple isolates of the same species. We also assessed their capacity to evade killing by the antibacterial peptide cathelicidin (LL-37). We discovered that the ability of different NTM species to infect macrophages varied among the species and among isolates of the same species. Our biochemical assays implicate modified phospholipids, which may include a phosphatidylinositol or cardiolipin backbone, as candidate antagonists of LL-37 antibacterial activity. The high variation in infectivity and virulence of NTM strains suggests that more detailed microbiological and biochemical characterizations are necessary to increase our knowledge of NTM pathogenesis.
临床重要的非结核分枝杆菌(NTM)种间的感染力比较尚未得到深入探讨。生长迅速的分枝杆菌,包括 和 ,可引起慢性但进行性的肺部疾病。 复合群中的缓慢生长成员是最常见的引起肺部疾病的 NTM 群,分子方法现在可以区分 复合群中的几个不同种,包括 、 、 和 。这些 NTM 种间的差异感染力可能部分解释了临床结果和治疗反应的差异;因此,了解特定分离株的相对感染力可以提高预后准确性并增强个体化治疗。我们使用人巨噬细胞研究了 9 种 NTM 种以及同种的多个分离株的感染力和毒力。我们还评估了它们逃避抗菌肽 cathelicidin (LL-37) 杀伤的能力。我们发现,不同 NTM 种感染巨噬细胞的能力在种间和同种分离株间存在差异。我们的生化分析表明,修饰的磷脂,包括磷脂酰肌醇或心磷脂骨架,可能是 LL-37 抗菌活性的拮抗剂候选物。NTM 菌株的感染力和毒力变化很大,这表明需要更详细的微生物学和生化特性来增加我们对 NTM 发病机制的了解。