丙氨酸消旋酶突变在结核分枝杆菌 D-环丝氨酸耐药中的作用。
Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance.
机构信息
Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand.
出版信息
Antimicrob Agents Chemother. 2017 Nov 22;61(12). doi: 10.1128/AAC.01575-17. Print 2017 Dec.
Abstract
A screening of more than 1,500 drug-resistant strains of revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to d-cycloserine.
摘要
对 1500 多种耐药株进行筛选，揭示了三个丙氨酸 racemase (Alr) 突变呈阳性选择特征的进化模式。我们使用分子建模、MIC 测试以及酶活性的直接测量来研究这些突变，结果表明这些突变可能导致对 d-环丝氨酸的耐药性。
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本文引用的文献
1
Assessment of Metabolic Changes in Mycobacterium smegmatis Wild-Type and alr Mutant Strains: Evidence of a New Pathway of d-Alanine Biosynthesis.
J Proteome Res. 2017 Mar 3;16(3):1270-1279. doi: 10.1021/acs.jproteome.6b00871. Epub 2017 Feb 14.
2
Mycobacterium tuberculosis drug-resistance testing: challenges, recent developments and perspectives.
Clin Microbiol Infect. 2017 Mar;23(3):154-160. doi: 10.1016/j.cmi.2016.10.022. Epub 2016 Nov 1.
3
Genomic and functional analyses of Mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance.
Nat Genet. 2016 May;48(5):544-51. doi: 10.1038/ng.3548. Epub 2016 Apr 11.
4
Sensititre MycoTB plate compared to Bactec MGIT 960 for first- and second-line antituberculosis drug susceptibility testing in Tanzania: a call to operationalize MICs.
Antimicrob Agents Chemother. 2015 Nov;59(11):7104-8. doi: 10.1128/AAC.01117-15. Epub 2015 Aug 24.
5
Unraveling Mycobacterium tuberculosis genomic diversity and evolution in Lisbon, Portugal, a highly drug resistant setting.
BMC Genomics. 2014 Nov 18;15(1):991. doi: 10.1186/1471-2164-15-991.
6
Metabolomics Reveal d-Alanine:d-Alanine Ligase As the Target of d-Cycloserine in .
ACS Med Chem Lett. 2013 Dec 12;4(12):1233-1237. doi: 10.1021/ml400349n. Epub 2013 Oct 5.
7
Whole genome sequencing reveals complex evolution patterns of multidrug-resistant Mycobacterium tuberculosis Beijing strains in patients.
PLoS One. 2013 Dec 6;8(12):e82551. doi: 10.1371/journal.pone.0082551. eCollection 2013.
8
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J Proteome Res. 2014 Feb 7;13(2):1065-76. doi: 10.1021/pr4010579. Epub 2013 Dec 13.
9
Whole-genome sequencing for rapid susceptibility testing of M. tuberculosis.
N Engl J Med. 2013 Jul 18;369(3):290-2. doi: 10.1056/NEJMc1215305.
10
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