Stepwise pathogenic evolution of Mycobacterium abscessus.
Stepwise pathogenic evolution of Mycobacterium abscessus.
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DOI：
10.1126/science.abb8699
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发表时间：
2021-04-30
期刊：
影响因子：
--
通讯作者：
Floto RA
中科院分区：
文献类型：
--
作者：
Bryant JM;Brown KP;Burbaud S;Everall I;Belardinelli JM;Rodriguez-Rincon D;Grogono DM;Peterson CM;Verma D;Evans IE;Ruis C;Weimann A;Arora D;Malhotra S;Bannerman B;Passemar C;Templeton K;MacGregor G;Jiwa K;Fisher AJ;Blundell TL;Ordway DJ;Jackson M;Parkhill J;Floto RA
虽然几乎所有的分枝杆菌物种都是有害的环境生物，但少数分枝杆菌，如结核分枝杆菌，已经进化到引起可传播的人类感染。通过分析最近出现的环境生物结核分枝杆菌通过全球囊性纤维化人群的传播，我们已经定义了分枝杆菌致病进化中涉及的关键，可推广的步骤。我们发现，通过水平基因转移获得的表观遗传修饰剂，导致特定环境克隆的致病潜力突变增加。慢性肺部感染期间的异域平行进化通过离散基因网络中的突变促进毒力的快速增加，该突变增强巨噬细胞内的生长但损害污染物存活。因此，我们观察到的限制致病进化，而人与人之间的传播仍然是间接的，但假设加速致病适应一旦直接传播是可能的，如M。结核我们的研究结果表明，关键的干预措施，如早期治疗和交叉感染控制，可能会限制现有的，并防止新的，紧急的分枝杆菌病原体。
While almost all mycobacterial species are saprophytic environmental organisms, a few, such as Mycobacterium tuberculosis, have evolved to cause transmissible human infection. By analysing the recent emergence and spread of the environmental organism Mycobacterium abscessus through the global Cystic Fibrosis population, we have defined key, generalisable steps involved in the pathogenic evolution of mycobacteria. We show that epigenetic modifiers, acquired through horizontal gene transfer, cause saltational increases in 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 that 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 existing, and prevent new, emergent mycobacterial pathogens.
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影响因子：
64.8
作者：
Bos KI;Harkins KM;Herbig A;Coscolla M;Weber N;Comas I;Forrest SA;Bryant JM;Harris SR;Schuenemann VJ;Campbell TJ;Majander K;Wilbur AK;Guichon RA;Wolfe Steadman DL;Cook DC;Niemann S;Behr MA;Zumarraga M;Bastida R;Huson D;Nieselt K;Young D;Parkhill J;Buikstra JE;Gagneux S;Stone AC;Krause J
通讯作者：
Krause J
影响因子：
48
作者：
Flusberg, Benjamin A.;Webster, Dale R.;Lee, Jessica H.;Travers, Kevin J.;Olivares, Eric C.;Clark, Tyson A.;Korlach, Jonas;Turner, Stephen W.
通讯作者：
Turner, Stephen W.
影响因子：
10
作者：
Floto RA;Olivier KN;Saiman L;Daley CL;Herrmann JL;Nick JA;Noone PG;Bilton D;Corris P;Gibson RL;Hempstead SE;Koetz K;Sabadosa KA;Sermet-Gaudelus I;Smyth AR;van Ingen J;Wallace RJ;Winthrop KL;Marshall BC;Haworth CS;US Cystic Fibrosis Foundation and European Cystic Fibrosis Society
通讯作者：
US Cystic Fibrosis Foundation and European Cystic Fibrosis Society
影响因子：
3.2
作者：
Dippenaar, Anzaan;Parsons, Sven David Charles;Warren, Robin Mark
通讯作者：
Warren, Robin Mark
影响因子：
3.1
作者：
Byrd, TF;Lyons, CR
通讯作者：
Lyons, CR