The genetic requirements for fast and slow growth in mycobacteria.
The genetic requirements for fast and slow growth in mycobacteria.
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DOI：
10.1371/journal.pone.0005349
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发表时间：
2009-04-28
期刊：
影响因子：
3.7
通讯作者：
McFadden J
中科院分区：
文献类型：
--
作者：
Beste DJ;Espasa M;Bonde B;Kierzek AM;Stewart GR;McFadden J
结核分枝杆菌感染了世界上三分之一的人口。涉及活跃的快速细菌复制的原发性结核病通常随后是无症状的潜伏性结核病，其特征是缓慢或非复制的细菌。潜伏感染的重新激活，包括转换回活跃的细菌复制，可导致原发后传染性结核病。分枝杆菌生长缓慢或转换生长速率的机制为开发抗持续性分枝杆菌感染的新药提供了合理的靶点。利用恒化培养控制生长速率的方法，通过转座子位点杂交（TraSH）筛选转座子突变体库，确定了牛分枝杆菌（Mycobacterium bovis，BCG）慢速和快速生长的遗传要求以及生长速率转换的遗传要求。我们确定了84个基因是专门为缓慢增长（69小时的倍增时间）和256个基因所需的转换从缓慢到快速增长。为了验证这些发现，我们使用单个M.结核和M.牛BCG敲除突变体。我们已经证明，生长速率控制是一个精心策划的过程，需要一套独特的基因编码几个毒力决定因子，基因调节因子和代谢酶。mce1基因座似乎是一个组成部分的开关，以缓慢的增长速度，这是一致的，在毒力的M。结核这些结果为阐明急性和持续性结核感染之间的转换机制提供了新的视角，并提供了一种在体外研究这一重要现象的方法。
Mycobacterium tuberculosis infects a third of the world's population. Primary tuberculosis involving active fast bacterial replication is often followed by asymptomatic latent tuberculosis, which is characterised by slow or non-replicating bacteria. Reactivation of the latent infection involving a switch back to active bacterial replication can lead to post-primary transmissible tuberculosis. Mycobacterial mechanisms involved in slow growth or switching growth rate provide rational targets for the development of new drugs against persistent mycobacterial infection. Using chemostat culture to control growth rate, we screened a transposon mutant library by Transposon site hybridization (TraSH) selection to define the genetic requirements for slow and fast growth of Mycobacterium bovis (BCG) and for the requirements of switching growth rate. We identified 84 genes that are exclusively required for slow growth (69 hours doubling time) and 256 genes required for switching from slow to fast growth. To validate these findings we performed experiments using individual M. tuberculosis and M. bovis BCG knock out mutants. We have demonstrated that growth rate control is a carefully orchestrated process which requires a distinct set of genes encoding several virulence determinants, gene regulators, and metabolic enzymes. The mce1 locus appears to be a component of the switch to slow growth rate, which is consistent with the proposed role in virulence of M. tuberculosis. These results suggest novel perspectives for unravelling the mechanisms involved in the switch between acute and persistent TB infections and provide a means to study aspects of this important phenomenon in vitro.
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影响因子：
3.1
作者：
Chen, P;Ruiz, RE;Bishai, WR
通讯作者：
Bishai, WR
影响因子：
3.2
作者：
Beste, D. J. V.;Laing, E.;McFadden, J. J.
通讯作者：
McFadden, J. J.
影响因子：
4.3
作者：
El Hajji, Miled;Rapaport, Alain
通讯作者：
Rapaport, Alain
影响因子：
56.9
作者：
ARRUDA, S;BOMFIM, G;RILEY, LW
通讯作者：
RILEY, LW
影响因子：
2.8
作者：
Karls, Russell K.;Guarner, Jeannette;Quinn, Frederick D.
通讯作者：
Quinn, Frederick D.