{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:56:01Z","timestamp":1787003761269,"version":"build-2736575974"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072246"],"award-info":[{"award-number":["82072246"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-024-06737-x","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T19:05:52Z","timestamp":1724439952000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Mycobacterium smegmatis MfpC is a GEF that regulates mfpA translationally to alter the fluoroquinolone efficacy"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4053-3648","authenticated-orcid":false,"given":"Yu","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinglei","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1388-5218","authenticated-orcid":false,"given":"Hongxiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0604-6901","authenticated-orcid":false,"given":"Peibo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9411-496X","authenticated-orcid":false,"given":"Lin","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8959-8146","authenticated-orcid":false,"given":"Jianping","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"6737_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.76","volume":"2","author":"M Pai","year":"2016","unstructured":"Pai, M. et al. Tuberculosis. Nat. Rev. Dis. Prim. 2, 16076 (2016).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"6737_CR2","unstructured":"Geneva. Global tuberculosis report 2022. (World Health Organisation, 2023)."},{"key":"6737_CR3","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1038\/s41570-023-00472-3","volume":"7","author":"V Singh","year":"2023","unstructured":"Singh, V., Dziwornu, G. A. & Chibale, K. The implication of Mycobacterium tuberculosis-mediated metabolism of targeted xenobiotics. Nat. Rev. Chem. 7, 340\u2013354 (2023).","journal-title":"Nat. Rev. Chem."},{"key":"6737_CR4","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1016\/j.drudis.2016.11.006","volume":"22","author":"V Nagaraja","year":"2017","unstructured":"Nagaraja, V., Godbole, A. A., Henderson, S. R. & Maxwell, A. DNA topoisomerase I and DNA gyrase as targets for TB therapy. Drug Discov. Today 22, 510\u2013518 (2017).","journal-title":"Drug Discov. Today"},{"key":"6737_CR5","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1093\/molbev\/msz214","volume":"37","author":"RAD Castro","year":"2020","unstructured":"Castro, R. A. D. et al. The genetic background modulates the evolution of Fluoroquinolone-resistance in Mycobacterium tuberculosis. Mol. Biol. Evol. 37, 195\u2013207 (2020).","journal-title":"Mol. Biol. Evol."},{"key":"6737_CR6","doi-asserted-by":"publisher","first-page":"3127","DOI":"10.1128\/AAC.00239-08","volume":"52","author":"O Danilchanka","year":"2008","unstructured":"Danilchanka, O., Pavlenok, M. & Niederweis, M. Role of porins for uptake of antibiotics by Mycobacterium smegmatis. Antimicrob. Agents Chemother. 52, 3127\u20133134 (2008).","journal-title":"Antimicrob. Agents Chemother."},{"key":"6737_CR7","doi-asserted-by":"publisher","first-page":"3175","DOI":"10.1128\/AAC.48.8.3175-3178.2004","volume":"48","author":"MR Pasca","year":"2004","unstructured":"Pasca, M. R. et al. Rv2686c-Rv2687c-Rv2688c, an ABC fluoroquinolone efflux pump in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 48, 3175\u20133178 (2004).","journal-title":"Antimicrob. Agents Chemother."},{"key":"6737_CR8","doi-asserted-by":"publisher","first-page":"3387","DOI":"10.1128\/AAC.45.12.3387-3392.2001","volume":"45","author":"C Montero","year":"2001","unstructured":"Montero, C., Mateu, G., Rodriguez, R. & Takiff, H. Intrinsic resistance of Mycobacterium smegmatis to fluoroquinolones may be influenced by new pentapeptide protein MfpA. Antimicrob. Agents Chemother. 45, 3387\u20133392 (2001).","journal-title":"Antimicrob. Agents Chemother."},{"key":"6737_CR9","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/S0140-6736(97)07322-4","volume":"351","author":"L Martinez-Martinez","year":"1998","unstructured":"Martinez-Martinez, L., Pascual, A. & Jacoby, G. A. Quinolone resistance from a transferable plasmid. Lancet 351, 797\u2013799 (1998).","journal-title":"Lancet"},{"key":"6737_CR10","doi-asserted-by":"publisher","first-page":"3400","DOI":"10.1016\/j.jmb.2019.05.050","volume":"431","author":"F Collin","year":"2019","unstructured":"Collin, F. & Maxwell, A. The Microbial Toxin Microcin B17: Prospects for the development of new antibacterial agents. J. Mol. Biol. 431, 3400\u20133426 (2019).","journal-title":"J. Mol. Biol."},{"key":"6737_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1021\/bi052130w","volume":"45","author":"MW Vetting","year":"2006","unstructured":"Vetting, M. W. et al. Pentapeptide repeat proteins. Biochemistry 45, 1\u201310 (2006).","journal-title":"Biochemistry"},{"key":"6737_CR12","doi-asserted-by":"publisher","unstructured":"Feng, L. et al. The pentapeptide-repeat protein, MfpA, interacts with mycobacterial DNA gyrase as a DNA T-segment mimic. Proc. Natl Acad. Sci. USA 118, https:\/\/doi.org\/10.1073\/pnas.2016705118 (2021).","DOI":"10.1073\/pnas.2016705118"},{"key":"6737_CR13","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1126\/science.1110699","volume":"308","author":"SS Hegde","year":"2005","unstructured":"Hegde, S. S. et al. A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science 308, 1480\u20131483 (2005).","journal-title":"Science"},{"key":"6737_CR14","doi-asserted-by":"publisher","first-page":"MGM2-0009-2013","DOI":"10.1128\/microbiolspec.MGM2-0009-2013","volume":"2","author":"C Mayer","year":"2014","unstructured":"Mayer, C. & Takiff, H. The molecular genetics of Fluoroquinolone resistance in mycobacterium tuberculosis. Microbiol. Spectr. 2, MGM2-0009-2013 (2014).","journal-title":"Microbiol. Spectr."},{"key":"6737_CR15","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1111\/j.1365-2958.2006.05461.x","volume":"62","author":"M Komatsu","year":"2006","unstructured":"Komatsu, M. et al. Proteins encoded by the conservon of Streptomyces coelicolor A3(2) comprise a membrane-associated heterocomplex that resembles eukaryotic G protein-coupled regulatory system. Mol. Microbiol. 62, 1534\u20131546 (2006).","journal-title":"Mol. Microbiol."},{"key":"6737_CR16","doi-asserted-by":"publisher","first-page":"2370","DOI":"10.1093\/nar\/gks1351","volume":"41","author":"J Tao","year":"2013","unstructured":"Tao, J. et al. Mycobacterium fluoroquinolone resistance protein B, a novel small GTPase, is involved in the regulation of DNA gyrase and drug resistance. Nucleic Acids Res. 41, 2370\u20132381 (2013).","journal-title":"Nucleic Acids Res."},{"key":"6737_CR17","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02098-22","volume":"10","author":"Y Huang","year":"2022","unstructured":"Huang, Y. et al. Mycobacterium Fluoroquinolone Resistance Protein D (MfpD), a GTPase-activating protein of GTPase MfpB, is involved in Fluoroquinolones potency. Microbiol. Spectr. 10, e0209822 (2022).","journal-title":"Microbiol. Spectr."},{"key":"6737_CR18","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.00281-21","volume":"6","author":"B Bonet","year":"2021","unstructured":"Bonet, B. et al. The cvn8 Conservon system is a global regulator of specialized metabolism in Streptomyces coelicolor during interspecies interactions. mSystems 6, e0028121 (2021).","journal-title":"mSystems"},{"key":"6737_CR19","doi-asserted-by":"publisher","first-page":"3271","DOI":"10.1099\/00221287-147-12-3271","volume":"147","author":"KG Papavinasasundaram","year":"2001","unstructured":"Papavinasasundaram, K. G. et al. Slow induction of RecA by DNA damage in Mycobacterium tuberculosis. Microbiology 147, 3271\u20133279 (2001).","journal-title":"Microbiology"},{"key":"6737_CR20","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1110\/ps.062117006","volume":"15","author":"V Jain","year":"2006","unstructured":"Jain, V., Saleem-Batcha, R., China, A. & Chatterji, D. Molecular dissection of the mycobacterial stringent response protein Rel. Protein Sci. 15, 1449\u20131464 (2006).","journal-title":"Protein Sci."},{"key":"6737_CR21","doi-asserted-by":"publisher","first-page":"11346","DOI":"10.1073\/pnas.0602817103","volume":"103","author":"A Singh","year":"2006","unstructured":"Singh, A., Mai, D., Kumar, A. & Steyn, A. J. Dissecting virulence pathways of Mycobacterium tuberculosis through protein-protein association. Proc. Natl Acad. Sci. USA 103, 11346\u201311351 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"6737_CR22","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1016\/j.cell.2007.05.018","volume":"129","author":"JL Bos","year":"2007","unstructured":"Bos, J. L., Rehmann, H. & Wittinghofer, A. GEFs and GAPs: critical elements in the control of small G proteins. Cell 129, 865\u2013877 (2007).","journal-title":"Cell"},{"key":"6737_CR23","doi-asserted-by":"publisher","first-page":"8287","DOI":"10.1021\/bi00098a002","volume":"30","author":"B Antonny","year":"1991","unstructured":"Antonny, B., Chardin, P., Roux, M. & Chabre, M. GTP hydrolysis mechanisms in ras p21 and in the ras-GAP complex studied by fluorescence measurements on tryptophan mutants. Biochemistry 30, 8287\u20138295 (1991).","journal-title":"Biochemistry"},{"key":"6737_CR24","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1126\/science.277.5324.333","volume":"277","author":"K Scheffzek","year":"1997","unstructured":"Scheffzek, K. et al. The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science 277, 333\u2013338, (1997).","journal-title":"Science"},{"key":"6737_CR25","doi-asserted-by":"publisher","first-page":"E25","DOI":"10.1038\/10018","volume":"1","author":"LA Feig","year":"1999","unstructured":"Feig, L. A. Tools of the trade: use of dominant-inhibitory mutants of Ras-family GTPases. Nat. Cell Biol. 1, E25\u201327 (1999).","journal-title":"Nat. Cell Biol."},{"key":"6737_CR26","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1128\/MMBR.00009-11","volume":"75","author":"N Verstraeten","year":"2011","unstructured":"Verstraeten, N., Fauvart, M., Versees, W. & Michiels, J. The universally conserved prokaryotic GTPases. Microbiol. Mol. Biol. Rev. 75, 507\u2013542 (2011).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"6737_CR27","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.gene.2011.01.005","volume":"477","author":"H Takano","year":"2011","unstructured":"Takano, H., Hashimoto, K., Yamamoto, Y., Beppu, T. & Ueda, K. Pleiotropic effect of a null mutation in the cvn1 conservon of Streptomyces coelicolor A3(2). Gene 477, 12\u201318 (2011).","journal-title":"Gene"},{"key":"6737_CR28","doi-asserted-by":"publisher","first-page":"e1000430","DOI":"10.1371\/journal.pbio.1000430","volume":"8","author":"Y Zhang","year":"2010","unstructured":"Zhang, Y., Franco, M., Ducret, A. & Mignot, T. A bacterial Ras-like small GTP-binding protein and its cognate GAP establish a dynamic spatial polarity axis to control directed motility. PLoS Biol. 8, e1000430 (2010).","journal-title":"PLoS Biol."},{"key":"6737_CR29","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1080\/15384101.2017.1282584","volume":"16","author":"P Ghosh","year":"2017","unstructured":"Ghosh, P., Rangamani, P. & Kufareva, I. The GAPs, GEFs, GDIs and\u2026now, GEMs: New kids on the heterotrimeric G protein signaling block. Cell Cycle 16, 607\u2013612 (2017).","journal-title":"Cell Cycle"},{"key":"6737_CR30","doi-asserted-by":"publisher","first-page":"2276","DOI":"10.1038\/emboj.2010.114","volume":"29","author":"S Leonardy","year":"2010","unstructured":"Leonardy, S. et al. Regulation of dynamic polarity switching in bacteria by a Ras-like G-protein and its cognate GAP. EMBO J. 29, 2276\u20132289 (2010).","journal-title":"EMBO J."},{"key":"6737_CR31","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1038\/s41564-019-0451-4","volume":"4","author":"D Szadkowski","year":"2019","unstructured":"Szadkowski, D. et al. Spatial control of the GTPase MglA by localized RomR-RomX GEF and MglB GAP activities enables Myxococcus xanthus motility. Nat. Microbiol. 4, 1344\u20131355 (2019).","journal-title":"Nat. Microbiol."},{"key":"6737_CR32","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6689186","volume":"2021","author":"A Falco","year":"2021","unstructured":"Falco, A., Aranaga, C., Ocampo, I. & Takiff, H. Overexpression of mfpA Gene increases Ciprofloxacin resistance in Mycobacterium smegmatis. Int J. Microbiol. 2021, 6689186 (2021).","journal-title":"Int J. Microbiol."},{"key":"6737_CR33","doi-asserted-by":"publisher","unstructured":"Yan, M. Y. et al. CRISPR-Cas12a-assisted recombineering in bacteria. Appl. Environ. Microbiol. 83, https:\/\/doi.org\/10.1128\/AEM.00947-17 (2017).","DOI":"10.1128\/AEM.00947-17"},{"key":"6737_CR34","doi-asserted-by":"publisher","unstructured":"Kanie, T. & Jackson, P. K. Guanine nucleotide exchange assay using fluorescent MANT-GDP. Bio. Protoc. 8, https:\/\/doi.org\/10.21769\/BioProtoc.2795 (2018).","DOI":"10.21769\/BioProtoc.2795"},{"key":"6737_CR35","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.tube.2010.09.006","volume":"91","author":"A Kapopoulou","year":"2011","unstructured":"Kapopoulou, A., Lew, J. M. & Cole, S. T. The MycoBrowser portal: a comprehensive and manually annotated resource for mycobacterial genomes. Tuberculosis 91, 8\u201313 (2011).","journal-title":"Tuberculosis"},{"key":"6737_CR36","doi-asserted-by":"publisher","first-page":"W320","DOI":"10.1093\/nar\/gku316","volume":"42","author":"X Robert","year":"2014","unstructured":"Robert, X. & Gouet, P. Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res. 42, W320\u2013324, (2014).","journal-title":"Nucleic Acids Res."},{"key":"6737_CR37","doi-asserted-by":"publisher","first-page":"D480","DOI":"10.1093\/nar\/gkaa1100","volume":"49","author":"C UniProt","year":"2021","unstructured":"UniProt, C. UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Res. 49, D480\u2013D489 (2021).","journal-title":"Nucleic Acids Res."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-06737-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-06737-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-06737-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T19:22:15Z","timestamp":1724440935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-06737-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,23]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["6737"],"URL":"https:\/\/doi.org\/10.1038\/s42003-024-06737-x","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,23]]},"assertion":[{"value":"30 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1035"}}