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Deletion of sigb causes increased sensitivity to para-aminosalicylic acid and sulfamethoxazole in mycobacterium tuberculosis
Yang, Shan-Shan1,2; Hu, Yang-Bo; Wang, Xu-De3,4; Gao, Yun-Rong5; Li, Kun1; Zhang, Xian-En6; Chen, Shi-Yun3; Zhang, Tian-Yu2,7; Gu, Ling1; Deng, Jiao-Yu1,8
刊名Antimicrobial agents and chemotherapy
2017-10-01
卷号61期号:10页码:12
关键词Mycobacterium tuberculosis Pabb Para-aminobenzoic acid Para-aminosalicylic acid Sigb
ISSN号0066-4804
DOI10.1128/aac.00551-17
通讯作者Gu, ling(gul@wh.iov.cn) ; Deng, jiao-yu(dengjy@wh.iov.cn)
英文摘要Although the de novo folate biosynthesis pathway has been well studied in bacteria, little is known about its regulation. in the present study, the sigb gene in mycobacterium tuberculosis was deleted. subsequent drug susceptibility tests revealed that the m. tuberculosis delta sigb strain was more sensitive to para-aminosalicylic acid (pas) and sulfamethoxazole. comparative transcriptional analysis was performed, and downregulation of pabb was observed in the delta sigb strain, which was further verified by a quantitative reverse transcription-pcr and western blot assay. then, the production levels of pora-aminobenzoic acid (paba) were compared between the sigb deletion mutant and wild-type strain, and the results showed that sigb deletion resulted in decreased production of paba. in addition, sigb was able to recognize the promoter of pabb in vitro. furthermore, we found that deleting pabc also caused increased susceptibility to pas. taken together, our data revealed that, in m. tuberculosis, sigb affects susceptibility to antifolates through multiple ways, primarily by regulating the expression of pabb. to our knowledge, this is the first report showing that sigb modulates paba biosynthesis and thus affecting susceptibility to antifolates, which broadens our understanding of the regulation of bacterial folate metabolism and mechanisms of susceptibility to antifolates.
WOS关键词PARA-AMINOBENZOATE SYNTHESIS ; GLOBAL GENE-EXPRESSION ; THYMIDYLATE SYNTHASE ; ESCHERICHIA-COLI ; AMINODEOXYCHORISMATE LYASE ; DIHYDROFOLATE-REDUCTASE ; PSEUDOMONAS-AERUGINOSA ; FOLIC-ACID ; RPOS GENE ; RESISTANCE
WOS研究方向Microbiology ; Pharmacology & Pharmacy
WOS类目Microbiology ; Pharmacology & Pharmacy
语种英语
出版者AMER SOC MICROBIOLOGY
WOS记录号WOS:000411481800009
内容类型期刊论文
URI标识http://www.corc.org.cn/handle/1471x/2373386
专题武汉病毒研究所
通讯作者Gu, Ling; Deng, Jiao-Yu
作者单位1.Chinese Acad Sci, Key Lab Special Pathogens & Biosafety, Wuhan Inst Virol, Wuhan, Hubei, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Chinese Acad Sci, Wuhan Inst Virol, Ctr Emerging Infect Dis, Key Lab Special Pathogens & Biosafety, Wuhan, Hubei, Peoples R China
4.Foshan Univ, Sch Stomatol & Med, Foshan, Peoples R China
5.Guangzhou Women & Children Med Ctr, Joint Ctr Translat Precis Med, Guangzhou Inst Pediat, Guangzhou, Guangdong, Peoples R China
6.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing, Peoples R China
7.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China
8.Guangdong Prov Key Lab TB Syst Biol & Translat Me, Foshan, Peoples R China
推荐引用方式
GB/T 7714
Yang, Shan-Shan,Hu, Yang-Bo,Wang, Xu-De,et al. Deletion of sigb causes increased sensitivity to para-aminosalicylic acid and sulfamethoxazole in mycobacterium tuberculosis[J]. Antimicrobial agents and chemotherapy,2017,61(10):12.
APA Yang, Shan-Shan.,Hu, Yang-Bo.,Wang, Xu-De.,Gao, Yun-Rong.,Li, Kun.,...&Deng, Jiao-Yu.(2017).Deletion of sigb causes increased sensitivity to para-aminosalicylic acid and sulfamethoxazole in mycobacterium tuberculosis.Antimicrobial agents and chemotherapy,61(10),12.
MLA Yang, Shan-Shan,et al."Deletion of sigb causes increased sensitivity to para-aminosalicylic acid and sulfamethoxazole in mycobacterium tuberculosis".Antimicrobial agents and chemotherapy 61.10(2017):12.
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