{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:59:54Z","timestamp":1793408394118,"version":"4.5.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-025-09107-3","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T12:37:56Z","timestamp":1764160676000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["ACA kills Mycobacterium tuberculosis and M. bovis by targeting cell wall core assembling protein CpsA"],"prefix":"10.1038","volume":"8","author":[{"given":"Feng","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengcong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0945-4095","authenticated-orcid":false,"given":"Zheng-Guo","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"9107_CR1","unstructured":"World Health Organization. Global tuberculosis report 2023. World Health Organization Geneva. https:\/\/iris.who.int\/handle\/10665\/373828 (WHO, 2023)."},{"key":"9107_CR2","doi-asserted-by":"publisher","first-page":"5202","DOI":"10.3390\/ijms24065202","volume":"24","author":"SSR Alsayed","year":"2023","unstructured":"Alsayed, S. S. R. & Gunosewoyo, H. Tuberculosis: pathogenesis, current treatment regimens and new drug targets. Int. J. Mol. Sci. 24, 5202 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"9107_CR3","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1126\/science.1106753","volume":"307","author":"K Andries","year":"2005","unstructured":"Andries, K. et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 307, 223\u2013227 (2005).","journal-title":"Science"},{"key":"9107_CR4","unstructured":"United States Food and Drug Administration. Sirturo (bedaquiline) NDA 204384 accelerated approval letter. United States Food and Drug Administration https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/appletter\/2012\/204384Orig1s000ltr.pdf (2012)."},{"key":"9107_CR5","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1093\/jac\/dkab505","volume":"77","author":"SE Mudde","year":"2022","unstructured":"Mudde, S. E., Upton, A. M., Lenaerts, A., Bax, H. I. & De Steenwinkel, J. E. M. Delamanid or pretomanid? A Solomonic judgement! J. Antimicrob. Chemother. 77, 880\u2013902 (2022).","journal-title":"J. Antimicrob. Chemother."},{"key":"9107_CR6","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41579-019-0273-7","volume":"18","author":"CL Dulberger","year":"2020","unstructured":"Dulberger, C. L., Rubin, E. J. & Boutte, C. C. The mycobacterial cell envelope-a moving target. Nat. Rev. Microbiol. 18, 47\u201359 (2020).","journal-title":"Nat. Rev. Microbiol."},{"key":"9107_CR7","doi-asserted-by":"publisher","first-page":"e1011318","DOI":"10.1371\/journal.ppat.1011318","volume":"19","author":"S Parmar","year":"2023","unstructured":"Parmar, S. & Tocheva, E. I. The cell envelope of Mycobacterium abscessus and its role in pathogenesis. PLoS Pathog. 19, e1011318 (2023).","journal-title":"PLoS Pathog."},{"key":"9107_CR8","doi-asserted-by":"crossref","unstructured":"Minnikin, D. E. et al. Pathophysiological implications of cell envelope structure in Mycobacterium tuberculosis and related taxa. Tuberculosis-expanding knowledge, 145-175 (Intech Open, 2015).","DOI":"10.5772\/59585"},{"key":"9107_CR9","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1021\/acs.jproteome.0c00650","volume":"20","author":"C Hermann","year":"2021","unstructured":"Hermann, C., Karamchand, L., Blackburn, J. M. & Soares, N. C. Cell envelope proteomics of mycobacteria. J. Proteome Res. 20, 94\u2013109 (2021).","journal-title":"J. Proteome Res."},{"key":"9107_CR10","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1146\/annurev-micro-091014-104121","volume":"69","author":"M Jankute","year":"2015","unstructured":"Jankute, M., Cox, J. A., Harrison, J. & Besra, G. S. Assembly of the mycobacterial cell wall. Annu. Rev. Microbiol. 69, 405\u2013423 (2015).","journal-title":"Annu. Rev. Microbiol."},{"key":"9107_CR11","doi-asserted-by":"publisher","first-page":"e00141","DOI":"10.1128\/CMR.00141-20","volume":"34","author":"SN Goossens","year":"2020","unstructured":"Goossens, S. N., Sampson, S. L. & Van Rie, A. Mechanisms of drug-induced tolerance in Mycobacterium tuberculosis. Clin. Microbiol. Rev. 34, e00141\u201320 (2020).","journal-title":"Clin. Microbiol. Rev."},{"key":"9107_CR12","doi-asserted-by":"publisher","first-page":"603382","DOI":"10.3389\/fcimb.2020.603382","volume":"10","author":"M Shaku","year":"2020","unstructured":"Shaku, M., Ealand, C. & Kana, B. D. Cell surface biosynthesis and remodeling pathways in mycobacteria reveal new drug targets. Front. Cell. Infect. Microbiol. 10, 603382 (2020).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"9107_CR13","doi-asserted-by":"publisher","first-page":"a021113","DOI":"10.1101\/cshperspect.a021113","volume":"5","author":"LJ Alderwick","year":"2015","unstructured":"Alderwick, L. J., Harrison, J., Lloyd, G. S. & Birch, H. L. The mycobacterial cell wall-peptidoglycan and arabinogalactan. Cold Spring Harb. Perspect. Med. 5, a021113 (2015).","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"9107_CR14","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1017\/S0031182016002377","volume":"145","author":"KA Abrahams","year":"2018","unstructured":"Abrahams, K. A. & Besra, G. S. Mycobacterial cell wall biosynthesis: a multifaceted antibiotic target. Parasitology 145, 116\u2013133 (2018).","journal-title":"Parasitology"},{"key":"9107_CR15","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1126\/science.8284673","volume":"263","author":"A Banerjee","year":"1994","unstructured":"Banerjee, A. et al. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 263, 227\u2013230 (1994).","journal-title":"Science"},{"key":"9107_CR16","doi-asserted-by":"publisher","first-page":"4138","DOI":"10.1128\/AAC.00162-09","volume":"53","author":"R Goude","year":"2009","unstructured":"Goude, R., Amin, A. G., Chatterjee, D. & Parish, T. The arabinosyltransferase EmbC is inhibited by ethambutol in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 53, 4138\u20134146 (2009).","journal-title":"Antimicrob. Agents Chemother."},{"key":"9107_CR17","doi-asserted-by":"publisher","first-page":"879775","DOI":"10.3389\/fimmu.2022.879775","volume":"13","author":"YY Li","year":"2022","unstructured":"Li, Y. Y. et al. Arabinogalactan enhances Mycobacterium marinum virulence by suppressing host innate immune responses. Front. Immunol. 13, 879775 (2022).","journal-title":"Front. Immunol."},{"key":"9107_CR18","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1186\/1471-2164-9-617","volume":"9","author":"J Hubscher","year":"2008","unstructured":"Hubscher, J., Luthy, L., Berger-Bachi, B. & Stutzmann Meier, P. Phylogenetic distribution and membrane topology of the LytR-CpsA-Psr protein family. BMC Genomics 9, 617 (2008).","journal-title":"BMC Genomics"},{"key":"9107_CR19","doi-asserted-by":"publisher","first-page":"4931","DOI":"10.1038\/emboj.2011.358","volume":"30","author":"Y Kawai","year":"2011","unstructured":"Kawai, Y. et al. A widespread family of bacterial cell wall assembly proteins. EMBO J. 30, 4931\u20134941 (2011).","journal-title":"EMBO J."},{"key":"9107_CR20","doi-asserted-by":"publisher","first-page":"2844","DOI":"10.1128\/IAI.03081-14","volume":"83","author":"Q Wang","year":"2015","unstructured":"Wang, Q. et al. CpsA, a LytR-CpsA-Psr family protein in Mycobacterium marinum, is required for cell wall integrity and virulence. Infect. Immun. 83, 2844\u20132854 (2015).","journal-title":"Infect. Immun."},{"key":"9107_CR21","doi-asserted-by":"publisher","first-page":"217","DOI":"10.3390\/microorganisms10020217","volume":"10","author":"A Rajaei","year":"2022","unstructured":"Rajaei, A., Rowe, H. M. & Neely, M. N. The LCP family protein, Psr, is required for cell wall integrity and virulence in Streptococcus agalactiae. Microorganisms 10, 217 (2022).","journal-title":"Microorganisms"},{"key":"9107_CR22","doi-asserted-by":"publisher","first-page":"557","DOI":"10.3389\/fmicb.2020.00557","volume":"11","author":"F Li","year":"2020","unstructured":"Li, F. et al. Impairment of the cell wall ligase, LytR-CpsA-Psr Protein (LcpC), in methicillin resistant Staphylococcus aureus reduces its resistance to antibiotics and infection in a mouse model of sepsis. Front. Microbiol. 11, 557 (2020).","journal-title":"Front. Microbiol."},{"key":"9107_CR23","doi-asserted-by":"publisher","first-page":"15680","DOI":"10.1074\/jbc.M114.567669","volume":"289","author":"YG Chan","year":"2014","unstructured":"Chan, Y. G., Kim, H., Schneewind, K. & Missiakas, O. D. The capsular polysaccharide of Staphylococcus aureus is attached to peptidoglycan by the LytR-CpsA-Psr (LCP) family of enzymes. J. Biol. Chem. 289, 15680\u201315690 (2014).","journal-title":"J. Biol. Chem."},{"key":"9107_CR24","doi-asserted-by":"publisher","first-page":"5859","DOI":"10.1128\/JB.00724-09","volume":"191","author":"O Johnsborg","year":"2009","unstructured":"Johnsborg, O. & Havarstein, L. S. Pneumococcal LytR, a protein from the LytR-CpsA-Psr family, is essential for normal septum formation in Streptococcus pneumoniae. J. Bacteriol. 191, 5859\u20135864 (2009).","journal-title":"J. Bacteriol."},{"key":"9107_CR25","doi-asserted-by":"publisher","first-page":"18867","DOI":"10.1074\/jbc.M116.739227","volume":"291","author":"AE Grzegorzewicz","year":"2016","unstructured":"Grzegorzewicz, A. E. et al. Assembling of the Mycobacterium tuberculosis cell wall core. J. Biol. Chem. 291, 18867\u201318879 (2016).","journal-title":"J. Biol. Chem."},{"key":"9107_CR26","doi-asserted-by":"publisher","first-page":"e00972-16","DOI":"10.1128\/mBio.00972-16","volume":"7","author":"J Harrison","year":"2016","unstructured":"Harrison, J. et al. Lcp1 is a phosphotransferase responsible for ligating arabinogalactan to peptidoglycan in Mycobacterium tuberculosis. mBio 7, e00972-16 (2016).","journal-title":"mBio"},{"key":"9107_CR27","doi-asserted-by":"publisher","first-page":"E8711","DOI":"10.1073\/pnas.1707792114","volume":"114","author":"S Koster","year":"2017","unstructured":"Koster, S. et al. Mycobacterium tuberculosis is protected from NADPH oxidase and LC3-associated phagocytosis by the LCP protein CpsA. Proc. Natl Acad. Sci. USA 114, E8711\u2013E8720 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"9107_CR28","doi-asserted-by":"publisher","first-page":"3936","DOI":"10.1038\/s41598-018-22012-6","volume":"8","author":"S Malm","year":"2018","unstructured":"Malm, S., Maass, S., Schaible, U. E., Ehlers, S. & Niemann, S. In vivo virulence of Mycobacterium tuberculosis depends on a single homologue of the LytR-CpsA-Psr proteins. Sci. Rep. 8, 3936 (2018).","journal-title":"Sci. Rep."},{"key":"9107_CR29","first-page":"1001","volume":"1","author":"T Cui","year":"2018","unstructured":"Cui, T., Zeng, J. & He, Z. G. Anti-tuberculosis drug target discovery by targeting the higher in-degree proteins (HidPs) of the pathogen\u2019s transcriptional network. J. Tuberc. 1, 1001 (2018).","journal-title":"J. Tuberc."},{"key":"9107_CR30","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1146\/annurev.bi.64.070195.000333","volume":"64","author":"PJ Brennan","year":"1995","unstructured":"Brennan, P. J. The envelope of mycobacteria. Annu. Rev. Biochem. 64, 29\u20136.1 (1995).","journal-title":"Annu. Rev. Biochem."},{"key":"9107_CR31","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/s41579-022-00731-y","volume":"20","author":"VA Dartois","year":"2022","unstructured":"Dartois, V. A. & Rubin, E. J. Anti-tuberculosis treatment strategies and drug development: challenges and priorities. Nat. Rev. Microbiol. 20, 685\u2013701 (2022).","journal-title":"Nat. Rev. Microbiol."},{"key":"9107_CR32","doi-asserted-by":"publisher","first-page":"S407","DOI":"10.1093\/clinids\/5.Supplement_3.S407","volume":"5","author":"W Wehrli","year":"1983","unstructured":"Wehrli, W. Rifampin: mechanisms of action and resistance. Rev. Infect. Dis. 5, S407\u2013S411 (1983).","journal-title":"Rev. Infect. Dis."},{"key":"9107_CR33","first-page":"1","volume":"2","author":"Y Zhang","year":"2013","unstructured":"Zhang, Y., Shi, W., Zhang, W. & Mitchison, D. Mechanisms of pyrazinamide action and resistance. Microbiol. Spectr. 2, 1\u201312 (2013).","journal-title":"Microbiol. Spectr."},{"key":"9107_CR34","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1046\/j.1365-2958.2000.02145.x","volume":"38","author":"RA Slayden","year":"2000","unstructured":"Slayden, R. A., Lee, R. E. & Barry, C. E. 3rd Isoniazid affects multiple components of the type II fatty acid synthase system of Mycobacterium tuberculosis. Mol. Microbiol. 38, 514\u2013525 (2000).","journal-title":"Mol. Microbiol."},{"key":"9107_CR35","doi-asserted-by":"publisher","first-page":"2484","DOI":"10.1128\/AAC.39.11.2484","volume":"39","author":"K Mikusova","year":"1995","unstructured":"Mikusova, K., Slayden, R. A., Besra, G. S. & Brennan, P. J. Biogenesis of the mycobacterial cell wall and the site of action of ethambutol. Antimicrob. Agents Chemother. 39, 2484\u20132489 (1995).","journal-title":"Antimicrob. Agents Chemother."},{"key":"9107_CR36","doi-asserted-by":"publisher","first-page":"222","DOI":"10.4103\/0976-500X.136121","volume":"5","author":"AS Xavier","year":"2014","unstructured":"Xavier, A. S. & Lakshmanan, M. Delamanid: a new armor in combating drug-resistant tuberculosis. J. Pharmacol. Pharmacother. 5, 222\u2013224 (2014).","journal-title":"J. Pharmacol. Pharmacother."},{"key":"9107_CR37","doi-asserted-by":"publisher","first-page":"2907","DOI":"10.1038\/ncomms3907","volume":"4","author":"S Lun","year":"2013","unstructured":"Lun, S. et al. Indoleamides are active against drug-resistant Mycobacterium tuberculosis. Nat. Commun. 4, 2907 (2013).","journal-title":"Nat. Commun."},{"key":"9107_CR38","doi-asserted-by":"publisher","first-page":"3369","DOI":"10.1038\/ncomms4369","volume":"5","author":"A Koul","year":"2014","unstructured":"Koul, A. et al. Delayed bactericidal response of Mycobacterium tuberculosis to bedaquiline involves remodelling of bacterial metabolism. Nat. Commun. 5, 3369 (2014).","journal-title":"Nat. Commun."},{"key":"9107_CR39","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1093\/nar\/gkr830","volume":"40","author":"M Yang","year":"2012","unstructured":"Yang, M., Gao, C., Cui, T., An, J. & He, Z. G. A TetR-like regulator broadly affects the expressions of diverse genes in Mycobacterium smegmatis. Nucleic Acids Res. 40, 1009\u20131020 (2012).","journal-title":"Nucleic Acids Res."},{"key":"9107_CR40","doi-asserted-by":"publisher","first-page":"e38276","DOI":"10.1371\/journal.pone.0038276","volume":"7","author":"F Huang","year":"2012","unstructured":"Huang, F. & He, Z. G. Characterization of a conserved interaction between DNA glycosylase and ParA in Mycobacterium smegmatis and M. tuberculosis. PLoS One 7, e38276 (2012).","journal-title":"PLoS One"},{"key":"9107_CR41","doi-asserted-by":"publisher","first-page":"541","DOI":"10.3389\/fmicb.2016.00541","volume":"7","author":"HJ Lee","year":"2016","unstructured":"Lee, H. J., Ko, H. J. & Jung, Y. J. Insufficient generation of mycobactericidal mediators and inadequate level of phagosomal maturation are related with susceptibility to virulent Mycobacterium tuberculosis infection in mouse macrophages. Front. Microbiol. 7, 541 (2016).","journal-title":"Front. Microbiol."},{"key":"9107_CR42","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.intimp.2018.11.013","volume":"66","author":"S Yan","year":"2019","unstructured":"Yan, S. et al. Mce-associated protein Rv0177 alters the cell wall structure of Mycobacterium smegmatis and promotes macrophage apoptosis via regulating the cytokines. Int. Immunopharmacol. 66, 205\u2013214 (2019).","journal-title":"Int. Immunopharmacol."},{"key":"9107_CR43","doi-asserted-by":"publisher","first-page":"31159","DOI":"10.1074\/jbc.M111.241802","volume":"286","author":"Y Wang","year":"2011","unstructured":"Wang, Y., Huang, Y., Xue, C., He, Y. & He, Z. G. ClpR protein-like regulator specifically recognizes RecA protein-independent promoter motif and broadly regulates expression of DNA damage-inducible genes in mycobacteria. J. Biol. Chem. 286, 31159\u201331167 (2011).","journal-title":"J. Biol. Chem."},{"key":"9107_CR44","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1111\/1462-2920.15249","volume":"23","author":"H Xu","year":"2021","unstructured":"Xu, H., Su, Z., Li, W., Deng, Y. & He, Z. G. MmbR, a master transcription regulator that controls fatty acid beta-oxidation genes in Mycolicibacterium smegmatis. Environ. Microbiol. 23, 1096\u20131114 (2021).","journal-title":"Environ. Microbiol."},{"key":"9107_CR45","doi-asserted-by":"publisher","first-page":"818881","DOI":"10.3389\/fmicb.2022.818881","volume":"13","author":"W Wei","year":"2022","unstructured":"Wei, W. et al. Dehydroquinate synthase directly binds to streptomycin and regulates susceptibility of Mycobacterium bovis to streptomycin in a non-canonical mode. Front. Microbiol. 13, 818881 (2022).","journal-title":"Front. Microbiol."},{"key":"9107_CR46","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1111\/imcb.1030","volume":"96","author":"Q Tan","year":"2018","unstructured":"Tan, Q. et al. Mutation analysis of the EBV-lymphoblastoid cell line cautions their use as antigen-presenting cells. Immunol. Cell Biol. 96, 204\u2013211 (2018).","journal-title":"Immunol. Cell Biol."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09107-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09107-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09107-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T14:04:12Z","timestamp":1764165852000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09107-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["9107"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-09107-3","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]},"assertion":[{"value":"8 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 November 2025","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":"1706"}}