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题名: RfiA, a novel PAP2 domain-containing polytopic membrane protein that confers resistance to the FtsZ inhibitor PC190723
作者: Chen, XM; Zhang, BL; Xiao, JX; Ju, FR; Li, SY; Ren, CL; An, LZ(安黎哲); Chen, T; Liu, GX; Facey, P; Mullins, JGL; Dyson, P
收录类别: SCIE ; PubMed ; MEDLINE
出版日期: 2015
刊名: FUTURE MICROBIOLOGY
卷号: 10, 期号:3, 页码:325-335
出版者: FUTURE MEDICINE LTD
出版地: LONDON
英文摘要: Background: As an essential protein for bacterial cell division, the tubulin-like FtsZ protein has been selected as a target for development of next generation antimicrobials. PC190723 is a fluoride-containing benzamide compound developed as a FtsZ inhibitor that selectively inhibits growth of multidrug resistant Gram-positive bacteria. Aim: Our aim was to investigate the mechanism of resistance to PC109723 conferred by over-expression of a gene, rfiA, in an environmental bacterium Arthrobacter A3. Materials & methods: The investigations included analysis of the effect of PC109723 on wild-type Arthrobacter A3 and a recombinant strain over-expressing rfiA, in vivo localization of RfiA, in vitro measurements of fluorine release from PC109723 by membrane extracts from the over-expression strain combined with mass spectrophotometric analysis of reaction products, and modelling of RfiA structure. Results: We describe a novel protein, RfiA, from Arthrobacter A3 that confers PC190723 resistance. RfiA is a PAP2 domain-containing polytopic transmembrane protein that can modify the fluoridated benzamide ring that is critical for high affinity binding of PC190723 with FtsZ. Conclusion: RfiA-mediated modification of PC190723 is the first reported instance of resistance to this antibiotic involving a change to its structure. We predict that adoption of PC190723 or related benzamides as antimicrobials in clinical practice will lead to the acquisition by resistant pathogens of a gene encoding this subfamily of proteins
关键词: antibiotic resistance ; cell cytoskeleton ; efflux ; FtsZ ; mechanisms of resistance
作者部门: [Chen, Ximing ; Zhang, Binglin ; Chen, Tuo ; Liu, Guangxiu] Lanzhou Univ, Key Lab Extreme Environm Microbial Resources & En, Lanzhou 730000, Gansu, Peoples R China ; [Chen, Ximing ; Zhang, Binglin ; Chen, Tuo ; Liu, Guangxiu] Lanzhou Univ, Chinese Acad Sci, Cold & Arid Reg Environm & Engn Res Inst, Key Lab Desert & Desertificat, Lanzhou 730000, Gansu, Peoples R China ; [Xiao, Jianxi ; Li, Shuyan ; Ren, Cuiling] Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Gansu, Peoples R China ; [Ju, Furong ; An, Lizhe] Lanzhou Univ, Sch Life Sci, Lanzhou 730000, Gansu, Peoples R China ; [Facey, Paul ; Mullins, Jonathan G. L. ; Dyson, Paul] Swansea Univ, Coll Med, Inst Life Sci, Swansea SA2 8PP, W Glam, Wales
通讯作者: Dyson, P (reprint author), Swansea Univ, Coll Med, Inst Life Sci, Singleton Pk, Swansea SA2 8PP, W Glam, Wales.
学科分类: Microbiology
文章类型: Article
所属项目编号: International S&T Cooperation Program of China [2011DFA32520] ; Chinese Academy Of Sciences Visiting Professorship for Senior International Scientists [2011T2Z34] ; National Natural Science Foundation of China [31400437] ; UK BBSRC China [BB/J020419/1]
所属项目名称: 国家自然科学基金项目 ; 国家国际科技合作专项 ; 英国生物技术与生物科学研究委员会项目
项目资助者: NSFC ; MOST ; BBSRC
语种: 英语
DOI: 10.2217/FMB.14.131
ISSN号: 1746-0913
WOS记录号: WOS:000351880700008
PM记录号: 25812456
IR记录号: WOS:000351880700008
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内容类型: 期刊论文
URI标识: http://ir.lzu.edu.cn/handle/262010/182080
Appears in Collections:资源环境学院_期刊论文

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Recommended Citation:
Chen, XM,Zhang, BL,Xiao, JX,et al. RfiA, a novel PAP2 domain-containing polytopic membrane protein that confers resistance to the FtsZ inhibitor PC190723[J]. FUTURE MICROBIOLOGY,2015,10(3):325-335.
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