{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:48:04Z","timestamp":1787593684295,"version":"build-2736575974"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb) secretes the low molecular weight protein tyrosine phosphatase B (PtpB), which disrupts key host innate immune defenses. This review synthesizes current knowledge regarding PtpB, highlighting its unique structural features, including a ubiquitin-activated dynamic lid that regulates its catalytic activity toward diverse substrates. PtpB is known to suppress pro-inflammatory cytokine production by dephosphorylating essential components of the MAPK and JAK-STAT signaling pathways. Additionally, upon activation by host ubiquitin, PtpB directly dephosphorylates plasma membrane lipids such as phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol 4,5-bisphosphate [PI (4,5)P2], thereby inhibiting the plasma membrane localization of gasdermin D and blocking pyroptosis. This review further evaluates the translational potential of targeting PtpB, emphasizing the discovery and structural characterization of potent, selective inhibitors. Ultimately, PtpB emerges as an attractive target for novel host-directed therapies against tuberculosis, especially in the face of rising drug resistance.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1833963","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:38:51Z","timestamp":1780547931000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The functions and inhibitors of protein tyrosine phosphatase B from Mycobacterium tuberculosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Haonan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital","place":["Jinan, Shandong, China"]},{"name":"Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital","place":["Jinan, Shandong, China"]},{"name":"Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dcit.2025.100044","article-title":"Who report signals tuberculosis resurgence: Addressing systemic failures and revamping control strategies","volume":"3","author":"Bashar Haruna","year":"2025","journal-title":"Decoding. Infect. Transm"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e93","DOI":"10.1164\/rccm.201909-1874ST","article-title":"Treatment of drug-resistant tuberculosis. An official ATS\/CDC\/ERS\/IDSA clinical practice guideline","volume":"200","author":"Nahid","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/nrmicro840","article-title":"Interplay between mycobacteria and host signalling pathways","volume":"2","author":"Koul","year":"2004","journal-title":"Nat Rev Microbiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1109201108","article-title":"Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H+-ATPase to inhibit phagosome acidification","volume":"108","author":"Wong","year":"2011","journal-title":"PNAS"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036198","article-title":"The fbpA\/sapM double knock out strain of Mycobacterium tuberculosis is highly attenuated and immunogenic in macrophages","volume":"7","author":"Saikolappan","year":"2012","journal-title":"PloS One"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2005.08.015","article-title":"Deciphering the genes involved in pathogenesis of Mycobacterium tuberculosis","volume":"85","author":"Singh","year":"2005","journal-title":"Tuberculosis. Edinburgh. Scotland."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077930","article-title":"Secretory phosphatases deficient mutant of Mycobacterium tuberculosis imparts protection at the primary site of infection in Guinea pigs","volume":"8","author":"Chauhan","year":"2013","journal-title":"PloS One"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1042\/bj20070670","article-title":"MptpB, a virulence factor from Mycobacterium tuberculosis, exhibits triple-specificity phosphatase activity","volume":"406","author":"Beresford","year":"2007","journal-title":"Biochem J"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq0132","article-title":"A bacterial phospholipid phosphatase inhibits host pyroptosis by hijacking ubiquitin","volume":"378","author":"Chai","year":"2022","journal-title":"Sci New. York. NY."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2023.04.007","article-title":"Mycobacterium tuberculosis and its secreted tyrosine phosphatases","volume":"212","author":"Chatterjee","year":"2023","journal-title":"Biochimie"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2022.140782","article-title":"Targeting protein tyrosine phosphatases for the development of antivirulence agents: Yersinia spp. and Mycobacterium tuberculosis as prototypes","volume":"1870","author":"Menegatti","year":"2022","journal-title":"Biochim Biophys Acta. Proteins Proteomics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/microorganisms9010014","article-title":"Therapeutic targeting of protein tyrosine phosphatases from Mycobacterium tuberculosis","volume":"9","author":"Ruddraraju","year":"2021","journal-title":"Microorganisms"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1042\/bst20201308","article-title":"Functional interrogation and therapeutic targeting of protein tyrosine phosphatases","volume":"49","author":"Krabill","year":"2021","journal-title":"Biochem Soc Trans"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2012.09.002","article-title":"Mycobacterium tuberculosis-secreted phosphatases: From pathogenesis to targets for TB drug development","volume":"21","author":"Wong","year":"2013","journal-title":"Trends Microbiol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2174\/0929867322666150812150036","article-title":"Mycobacterium tuberculosis low molecular weight phosphatases (MPtpA and MPtpB): From biological insight to inhibitors","volume":"22","author":"Fanzani","year":"2015","journal-title":"Curr Med Chem"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.5582\/ddt.2022.01104","article-title":"Suppressing host pyroptosis by a ubiquitin-activated phospholipid phosphatase of Mycobacterium tuberculosis","volume":"17","author":"Feng","year":"2023","journal-title":"Drug Discoveries. Ther"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.11.020","article-title":"Mycobacterium tuberculosis hijacks ubiquitin to inhibit pyroptosis","volume":"82","author":"Krause","year":"2022","journal-title":"Mol Cell"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03712.x","article-title":"Disruption of mptpB impairs the ability of Mycobacterium tuberculosis to survive in Guinea pigs","volume":"50","author":"Singh","year":"2003","journal-title":"Mol Microbiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.str.2007.03.003","article-title":"Structural basis for selective inhibition of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB","volume":"15","author":"Grundner","year":"2007","journal-title":"Structure. Lond. Engl 1993."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077081","article-title":"Discovery of Mycobacterium tuberculosis protein tyrosine phosphatase B (PtpB) inhibitors from natural products","volume":"8","author":"Mascarello","year":"2013","journal-title":"PloS One"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2005.07.017","article-title":"Mycobacterium tuberculosis protein tyrosine phosphatase PtpB structure reveals a diverged fold and a buried active site","volume":"13","author":"Grundner","year":"2005","journal-title":"Structure. Lond. Engl 1993."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1850009","article-title":"Post translational modifications in tuberculosis: Ubiquitination paradox","volume":"17","author":"Shariq","year":"2021","journal-title":"Autophagy"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1095060","article-title":"Characteristics of Mycobacterium tuberculosis PtpA interaction and activity on the alpha subunit of human mitochondrial trifunctional protein, a key enzyme of lipid metabolism","volume":"13","author":"Margenat","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jmb.2011.08.015","article-title":"Structure and substrate recognition of the Staphylococcus aureus protein tyrosine phosphatase PtpA","volume":"413","author":"Vega","year":"2011","journal-title":"J Mol Biol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1754992","article-title":"Research progress on protein tyrosine phosphatase A from Mycobacterium tuberculosis","volume":"16","author":"Cai","year":"2025","journal-title":"Front Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.399261","article-title":"The apo-structure of the low molecular weight protein-tyrosine phosphatase A (MptpA) from Mycobacterium tuberculosis allows for better target-specific drug development","volume":"287","author":"Stehle","year":"2012","journal-title":"J Biol Chem"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nature18629","article-title":"Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores","volume":"535","author":"Liu","year":"2016","journal-title":"Nature"},{"key":"B28","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41420-021-00716-5","article-title":"Gasdermin D mediates host cell death but not interleukin-1\u03b2 secretion in Mycobacterium tuberculosis-infected macrophages","volume":"7","author":"Theobald","year":"2021","journal-title":"Cell Death Discov"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a036400","article-title":"Mechanism and regulation of gasdermin-mediated cell death","volume":"12","author":"Xia","year":"2020","journal-title":"Cold Spring Harbor Perspect Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00832","article-title":"Structure-based design of MptpB inhibitors that reduce multidrug-resistant Mycobacterium tuberculosis survival and infection burden in vivo","volume":"61","author":"Vickers","year":"2018","journal-title":"J Med Chem"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00171","article-title":"MptpB promotes mycobacteria survival by inhibiting the expression of inflammatory mediators and cell apoptosis in macrophages","volume":"8","author":"Fan","year":"2018","journal-title":"Front Cell Infect Microbiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2025.101067","article-title":"Mycobacterial tyrosine phosphatase PtpB affects host cytokine expression by dephosphorylating ERK1\/2 and STAT3","volume":"24","author":"Liu","year":"2025","journal-title":"Mol Cell Proteomics MCP."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909133107","article-title":"Targeting mycobacterium protein tyrosine phosphatase B for antituberculosis agents","volume":"107","author":"Zhou","year":"2010","journal-title":"PNAS"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1021\/jm060327w","article-title":"Brunsvicamides A-C: Sponge-related cyanobacterial peptides with Mycobacterium tuberculosis protein tyrosine phosphatase inhibitory activity","volume":"49","author":"M\u00fcller","year":"2006","journal-title":"J Med Chem"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/asia.200700125","article-title":"Identification of inhibitors for mycobacterial protein tyrosine phosphatase B (MptpB) by biology-oriented synthesis (BIOS)","volume":"2","author":"Corr\u00eaa","year":"2007","journal-title":"Chem Asian J"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1021\/jm301781p","article-title":"Discovery and evaluation of novel inhibitors of mycobacterium protein tyrosine phosphatase B from the 6-hydroxy-benzofuran-5-carboxylic acid scaffold","volume":"56","author":"He","year":"2013","journal-title":"J Med Chem"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104495","article-title":"Identification of fusarielin M as a novel inhibitor of Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB)","volume":"106","author":"Chen","year":"2021","journal-title":"Bioorg. Chem"},{"key":"B38","doi-asserted-by":"publisher","first-page":"381","DOI":"10.3390\/md18080381","article-title":"Bioactive metabolites from the deep-sea-derived fungus Diaporthe longicolla FS429","volume":"18","author":"Liu","year":"2020","journal-title":"Mar Drugs"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-s1-s3","article-title":"Structural insights into mode of actions of novel natural Mycobacterium protein tyrosine phosphatase B inhibitors","author":"Dhanjal","year":"2014","journal-title":"BMC Genomics"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3390\/md12052953","article-title":"Alterporriol-type dimers from the mangrove endophytic fungus, Alternaria sp. (SK11), and their MptpB inhibitions","volume":"12","author":"Xia","year":"2014","journal-title":"Mar Drugs"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/md13010366","article-title":"Asperlones A and B, dinaphthalenone derivatives from a mangrove endophytic fungus Aspergillus sp. 16-5C","volume":"13","author":"Xiao","year":"2015","journal-title":"Mar Drugs"},{"key":"B42","doi-asserted-by":"publisher","first-page":"319","DOI":"10.3390\/md16090319","article-title":"Lead compounds from mangrove-associated microorganisms","volume":"16","author":"Ancheeva","year":"2018","journal-title":"Mar Drugs"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107667","article-title":"Pyrimidine-based sulfonamides and acetamides as potent antimicrobial agents: Synthesis, computational studies, and biological assessment","volume":"151","author":"Indalkar","year":"2024","journal-title":"Bioorg. Chem"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114235","article-title":"Virtual screening and crystallographic studies reveal an unexpected \u03b3-lactone derivative active against MptpB as a potential antitubercular agent","volume":"234","author":"Cazzaniga","year":"2022","journal-title":"Eur J Med Chem"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp031","article-title":"Inhibition of MptpB phosphatase from Mycobacterium tuberculosis impairs mycobacterial survival in macrophages","volume":"63","author":"Beresford","year":"2009","journal-title":"J Antimicrob Chemother"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1021\/ol9023419","article-title":"High-throughput discovery of Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) inhibitors using click chemistry","volume":"11","author":"Tan","year":"2009","journal-title":"Org. Lett"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201000348","article-title":"Double click reaction for the acquisition of a highly potent and selective mPTPB inhibitor","volume":"5","author":"He","year":"2010","journal-title":"ChemMedChem"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201002138","article-title":"Identification of thiazolidinones spiro-fused to indolin-2-ones as potent and selective inhibitors of the Mycobacterium tuberculosis protein tyrosine phosphatase B","volume":"49","author":"Vintonyak","year":"2010","journal-title":"Angewandte. Chemie. International. Ed. English."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1039\/c3cc38961h","article-title":"Organocatalytic multicomponent reaction for the acquisition of a selective inhibitor of mPTPB, a virulence factor of tuberculosis","volume":"49","author":"He","year":"2013","journal-title":"Chem Commun (Cambridge Engl."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2018.12.009","article-title":"Synthesis, biological evaluation and molecular docking study of 1,2,3-1H-triazoles having 4H-pyrano[2,3-d]pyrimidine as potential Mycobacterium tuberculosis protein tyrosine phosphatase B inhibitors","volume":"29","author":"Thanh","year":"2019","journal-title":"Bioorg. Med Chem Lett"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2018.12.038","article-title":"Docking- and pharmacophore-based virtual screening for the identification of novel Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) inhibitor with a thiobarbiturate scaffold","volume":"85","author":"Zhang","year":"2019","journal-title":"Bioorg. Chem"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2022.117006","article-title":"Discovery of biphenyls bearing thiobarbiturate fragment by structure-based strategy as Mycobacterium tuberculosis protein tyrosine phosphatase B inhibitors","volume":"73","author":"Cheng","year":"2022","journal-title":"Bioorg. Med Chem"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00302","article-title":"Highly potent and selective N-aryl oxamic acid-based inhibitors for Mycobacterium tuberculosis protein tyrosine phosphatase B","volume":"63","author":"Ruddraraju","year":"2020","journal-title":"J Med Chem"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115571","article-title":"Design, synthesis and biological evaluation of 3-substituted-2-thioxothiazolidin-4-one (rhodanine) derivatives as antitubercular agents against Mycobacterium tuberculosis protein tyrosine phosphatase B","volume":"258","author":"Cheng","year":"2023","journal-title":"Eur J Med Chem"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1039\/c0ob00182a","article-title":"Design and synthesis of nonpeptidic, small molecule inhibitors for the Mycobacterium tuberculosis protein tyrosine phosphatase PtpB","volume":"8","author":"Rawls","year":"2010","journal-title":"Organic. Biomolecular. Chem"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1833963\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:38:55Z","timestamp":1780547935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1833963\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,4]]},"references-count":55,"alternative-id":["10.3389\/fimmu.2026.1833963"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1833963","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,4]]},"article-number":"1833963"}}