近日，英国剑桥大学R. Andres Floto及其课题组揭示脓肿分枝杆菌的逐步致病性演化。2021年4月30日出版的《科学》杂志发表了这项成果。
通过分析环境微生物脓肿分枝杆菌近期在全球囊性纤维化人群中的出现和传播，研究人员确定了分枝杆菌致病性进化所涉及的关键步骤。研究人员表明，通过水平基因转移获得的表观遗传修饰因子在特定环境克隆的致病性中引起了突变的增加。慢性肺部感染期间的异源平行进化随后通过离散基因网络中的突变促进了毒力的快速增加。
这些突变增强了巨噬细胞内的生长，但损害了病媒的存活。因此，研究人员观察到了受约束的病原体演化，而人与人之间的传播仍然是间接的，但一旦直接传播成为可能，就表明了病原体适应的加速，如在结核分枝杆菌中所观察到的。这些发现表明，关键干预措施（如早期治疗和交叉感染控制）可能限制现有分枝杆菌病原体的传播并预防新出现的病原体。
据介绍，尽管几乎所有分枝杆菌属物种都是腐生性环境生物，但一些细菌（如结核分枝杆菌）已经进化为可传播的人类传染病。
附：英文原文
Title: Stepwise pathogenic evolution of Mycobacterium abscessus
Author: Josephine M. Bryant, Karen P. Brown, Sophie Burbaud, Isobel Everall, Juan M. Belardinelli, Daniela Rodriguez-Rincon, Dorothy M. Grogono, Chelsea M. Peterson, Deepshikha Verma, Ieuan E. Evans, Christopher Ruis, Aaron Weimann, Divya Arora, Sony Malhotra, Bridget Bannerman, Charlotte Passemar, Kerra Templeton, Gordon MacGregor, Kasim Jiwa, Andrew J. Fisher, Tom L. Blundell, Diane J. Ordway, Mary Jackson, Julian Parkhill, R. Andres Floto
Issue&Volume: 2021/04/30
Abstract: Although almost all mycobacterial species are saprophytic environmental organisms, a few, such as Mycobacterium tuberculosis, have evolved to cause transmissible human infection. By analyzing the recent emergence and spread of the environmental organism M. abscessus through the global cystic fibrosis population, we have defined key, generalizable steps involved in the pathogenic evolution of mycobacteria. We show that epigenetic modifiers, acquired through horizontal gene transfer, cause saltational increases in the pathogenic potential of specific environmental clones. Allopatric parallel evolution during chronic lung infection then promotes rapid increases in virulence through mutations in a discrete gene network; these mutations enhance growth within macrophages but impair fomite survival. As a consequence, we observe constrained pathogenic evolution while person-to-person transmission remains indirect, but postulate accelerated pathogenic adaptation once direct transmission is possible, as observed for M. tuberculosis. Our findings indicate how key interventions, such as early treatment and cross-infection control, might restrict the spread of existing mycobacterial pathogens and prevent new, emergent ones.
DOI: 10.1126/science.abb8699
Source: https://science.sciencemag.org/content/372/6541/eabb8699