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 |
DOI | 10.1128/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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