دورية أكاديمية

Association between mutations in a thyX-hsdS.1 region and para -aminosalicylic acid resistance in Mycobacterium tuberculosis clinical isolates.

التفاصيل البيبلوغرافية
العنوان: Association between mutations in a thyX-hsdS.1 region and para -aminosalicylic acid resistance in Mycobacterium tuberculosis clinical isolates.
المؤلفون: Zeng R; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.; University of Chinese Academy of Sciences, Beijing, People's Republic of China., He L; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.; University of Chinese Academy of Sciences, Beijing, People's Republic of China., Zhang B; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.; University of Chinese Academy of Sciences, Beijing, People's Republic of China., Hu Y; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China., Yu J; Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China., Yang S; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China., Gu J; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China., Wu Z; Department of Tuberculosis Control, The Fourth People's Hospital of Foshan City, Foshan, People's Republic of China., Deng J; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
المصدر: Emerging microbes & infections [Emerg Microbes Infect] 2023 Dec; Vol. 12 (2), pp. 2276339. Date of Electronic Publication: 2023 Nov 29.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101594885 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2222-1751 (Electronic) Linking ISSN: 22221751 NLM ISO Abbreviation: Emerg Microbes Infect Subsets: MEDLINE
أسماء مطبوعة: Publication: 2019- : [Philadelphia, PA] : Taylor & Francis
Original Publication: New York : NPG, 2012-2018.
مواضيع طبية MeSH: Aminosalicylic Acid*/pharmacology , Mycobacterium tuberculosis* , Tuberculosis*/drug therapy, Humans ; Mutation ; Antitubercular Agents/pharmacology ; Bacterial Proteins/genetics ; Microbial Sensitivity Tests
مستخلص: Although para -aminosalicylic acid (PAS) has been used to treat tuberculosis agent for decades, its mechanisms of resistance are still not thoroughly understood. Previously, sporadic studies showed that certain mutations in the thyX-hsdS.1 region caused PAS resistance in M. tuberculosis , but a comprehensive analysis is lacking. Recently, we found a G-10A mutation in thyX-hsdS.1 in a PAS-resistant clinical isolate, but it did not cause PAS resistance. SNPs in thyX-hsdS.1 in 6550 clinical isolates were analyzed, and 153 SNPs were identified. C-16 T was the most common SNP identified (54.25%, 83/153), followed by C-4T (7.19%, 11/153) and G-9A (6.54%, 10/153). Subsequently, the effects of those SNPs on the promoter activity of thyX were tested, and the results showed that mutations C-1T, G-3A, C-4T, C-4G, G-7A, G-9A, C-16T, G-18C, and C-19G led to increased promoter activity compared with the wild-type sequence, but other mutations did not. Then, thyX and wild-type thyX-hsdS.1 , or thyX-hsdS.1 containing specific SNPs, were overexpressed in M. tuberculosis H37Ra. The results showed that mutations resulting in increased promoter activity also caused PAS resistance. Moreover, the results of an electrophoretic mobility shift assay showed that thyX-hsdS.1 containing the C-16T mutation had a higher binding capacity to RNA polymerase than did the wild-type sequence. Taken together, our data demonstrated that among the SNPs identified in thyX-hsdS.1 of M. tuberculosis clinical isolates, only those able to increase the promoter activity of thyX caused PAS resistance and therefore can be considered as molecular markers for PAS resistance.
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فهرسة مساهمة: Keywords: Mycobacterium tuberculosis; PAS; mutations; resistance; thyX-hsdS.1
المشرفين على المادة: 5B2658E0N2 (Aminosalicylic Acid)
0 (Antitubercular Agents)
0 (Bacterial Proteins)
تواريخ الأحداث: Date Created: 20231129 Date Completed: 20231201 Latest Revision: 20240108
رمز التحديث: 20240108
مُعرف محوري في PubMed: PMC10769527
DOI: 10.1080/22221751.2023.2276339
PMID: 38029724
قاعدة البيانات: MEDLINE
الوصف
تدمد:2222-1751
DOI:10.1080/22221751.2023.2276339