Comparative genomics for mycobacterial peptidoglycan remodelling enzymes reveals extensive genetic multiplicity.
Comparative genomics for mycobacterial peptidoglycan remodelling enzymes reveals extensive genetic multiplicity.
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DOI：
10.1186/1471-2180-14-75
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发表时间：
2014-03-24
期刊：
影响因子：
4.2
通讯作者：
Kana BD
中科院分区：
文献类型：
--
作者：
Machowski EE;Senzani S;Ealand C;Kana BD
分枝杆菌包括不同的物种，包括非致病性的环境生物体、动物病原体和人类病原体，特别是结核分枝杆菌。考虑到分枝杆菌细胞壁构成了药物渗透的重要屏障，本研究的目的是对参与肽聚糖（PG）重塑的酶进行比较基因组学分析，以确定利用细菌代谢这一领域发现新药物靶点的潜力。我们对19种分枝杆菌/临床菌株进行了计算机模拟分析，以确定是否存在编码复苏促进因子（Rpfs）、青霉素结合蛋白、内肽酶、L，D-转肽酶和N-乙酰胞壁酰-L-丙氨酸酰胺酶的基因。我们的分析揭示了广泛的遗传多样性，允许分枝杆菌物种分为三个主要类别，主要是基于他们的rpf基因互补的分类。其中包括M。结核复合体（MTBC）、其他致病性分枝杆菌和环境物种。这些基因在MTBC和其他分枝杆菌病原体中的互补是高度保守的。相反，环境菌株在大多数这些基因家族中显示出显着的遗传扩展。麻风分枝杆菌保留一个以上的功能基因，从每个酶家族，强调PG重塑的重要性，遗传多样性。值得注意的是，对于N-乙酰胞壁酰-L-丙氨酸酰胺酶观察到最高程度的保守性，表明这些酶对于生长和存活是必需的。PG重塑酶在一系列的分枝杆菌物种与广泛的遗传多样性，这表明功能多样性在这些家庭的酶，使生物体适应。
Mycobacteria comprise diverse species including non-pathogenic, environmental organisms, animal disease agents and human pathogens, notably Mycobacterium tuberculosis. Considering that the mycobacterial cell wall constitutes a significant barrier to drug penetration, the aim of this study was to conduct a comparative genomics analysis of the repertoire of enzymes involved in peptidoglycan (PG) remodelling to determine the potential of exploiting this area of bacterial metabolism for the discovery of new drug targets. We conducted an in silico analysis of 19 mycobacterial species/clinical strains for the presence of genes encoding resuscitation promoting factors (Rpfs), penicillin binding proteins, endopeptidases, L,D-transpeptidases and N-acetylmuramoyl-L-alanine amidases. Our analysis reveals extensive genetic multiplicity, allowing for classification of mycobacterial species into three main categories, primarily based on their rpf gene complement. These include the M. tuberculosis Complex (MTBC), other pathogenic mycobacteria and environmental species. The complement of these genes within the MTBC and other mycobacterial pathogens is highly conserved. In contrast, environmental strains display significant genetic expansion in most of these gene families. Mycobacterium leprae retains more than one functional gene from each enzyme family, underscoring the importance of genetic multiplicity for PG remodelling. Notably, the highest degree of conservation is observed for N-acetylmuramoyl-L-alanine amidases suggesting that these enzymes are essential for growth and survival. PG remodelling enzymes in a range of mycobacterial species are associated with extensive genetic multiplicity, suggesting functional diversification within these families of enzymes to allow organisms to adapt.
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影响因子：
2.8
作者：
Dasgupta, A;Datta, P;Basu, J
通讯作者：
Basu, J
影响因子：
6.7
作者：
Chao, Michael C.;Kieser, Karen J.;Rubin, Eric J.
通讯作者：
Rubin, Eric J.
影响因子：
3.1
作者：
Downing, KJ;Mischenko, VV;Mizrahi, V
通讯作者：
Mizrahi, V
影响因子：
3.9
作者：
Besra, GS;Brennan, PJ
通讯作者：
Brennan, PJ
DOI：
10.1107/s0907444912049268
发表时间：
2013-03-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Both, Dominic;Steiner, Eva Maria;Schneider, Gunter
通讯作者：
Schneider, Gunter