Bachmann Nathan L, Salamzade Rauf, Manson Abigail L, Whittington Richard, Sintchenko Vitali, Earl Ashlee M, Marais Ben J
NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research - Pathology West, Sydney, NSW, Australia.
Centre for Research Excellence in Tuberculosis and the Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, NSW, Australia.
Front Microbiol. 2020 Jan 21;10:3019. doi: 10.3389/fmicb.2019.03019. eCollection 2019.
Mycobacteria have been classified into rapid and slow growing phenotypes, but the genetic factors that underlie these growth rate differences are not well understood. We compared the genomes of 157 mycobacterial species, representing all major branches of the mycobacterial phylogenetic tree to identify genes and operons enriched among rapid and slow growing mycobacteria. Overlaying growth phenotype on a phylogenetic tree based on 304 core genes suggested that ancestral mycobacteria had a rapid growth phenotype with a single major evolutionary separation into rapid and slow growing sub-genera. We identified 293 genes enriched among rapid growing sub-genera, including genes encoding for amino acid transport/metabolism (e.g., operon) and transcription, as well as novel ABC transporters. Loss of the and ABC transporter operons among slow growing species suggests that reduced cellular amino acid transport may be growth limiting. Comparative genomic analysis suggests that horizontal gene transfer, from non-mycobacterial genera, may have contributed to niche adaptation and pathogenicity, especially among slow growing species. Interestingly, the mammalian cell entry () operon was found to be ubiquitous, irrespective of growth phenotype or pathogenicity, although protein sequence homology between rapid and slow growing species was low (<50%). This suggests that the operon was present in ancestral rapid growing species, but later adapted by slow growing species for use as a mechanism to establish an intra-cellular lifestyle.
分枝杆菌已被分为快速生长和缓慢生长的表型，但导致这些生长速率差异的遗传因素尚未完全了解。我们比较了157种分枝杆菌的基因组，这些基因组代表了分枝杆菌系统发育树的所有主要分支，以鉴定在快速生长和缓慢生长的分枝杆菌中富集的基因和操纵子。基于304个核心基因的系统发育树上叠加生长表型表明，祖先分枝杆菌具有快速生长表型，在进化过程中主要分为快速生长和缓慢生长的亚属。我们鉴定出293个在快速生长亚属中富集的基因，包括编码氨基酸转运/代谢（如操纵子）和转录的基因，以及新型ABC转运蛋白。缓慢生长物种中某些基因和ABC转运蛋白操纵子的缺失表明，细胞氨基酸转运减少可能限制了生长。比较基因组分析表明，来自非分枝杆菌属的水平基因转移可能有助于生态位适应和致病性，特别是在缓慢生长的物种中。有趣的是，发现哺乳动物细胞进入（）操纵子普遍存在，无论生长表型或致病性如何，尽管快速生长和缓慢生长物种之间的蛋白质序列同源性较低（<50%）。这表明该操纵子存在于祖先快速生长的物种中，但后来被缓慢生长的物种所采用，作为建立细胞内生存方式的一种机制。
