{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:52:07Z","timestamp":1787986327264,"version":"build-2784847793"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"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. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>MPT64 protein is an effective marker for detecting <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (MTB) in liquid culture and clinical tissue samples. However, some MTB clinical isolates test negative for this antigen because of varied mutation types across different regions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DNA samples of MPT64 antigen assay-negative MTB strains were collected from a tertiary hospital from January 2016 to January 2024, and <jats:italic>mpt64<\/jats:italic> gene mutations were detected by sequencing. Clinical records of patients with negative MPT64 antigen results were collected and compared with those of patients with positive results. The global distribution of <jats:italic>mpt64<\/jats:italic> gene mutations was analyzed using MTB genome sequences from the National Center for Biotechnology Information (NCBI) database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 821 mycobacterial specimens with negative MPT64 antigen assay results, 77 MTB strains were collected from 73 patients. Compared with MPT64-positive patients (<jats:italic>n<\/jats:italic> = 301), a higher percentage of MPT64-negative patients had a history of anti-tuberculosis therapy (<jats:italic>n<\/jats:italic> = 7, 11.1%; <jats:italic>P<\/jats:italic> = 0.01). Moreover, MPT64-negative patients demonstrated a lower percentage of positive Gene Xpert results than MPT64-positive patients (73.8% vs 95.1%, <jats:italic>P<\/jats:italic> &amp;lt; 0.001). Several gene mutations were detected in the MPT64-negative MTB strains, including 63 bp deletion, single nucleotide mutations, and <jats:italic>IS6110<\/jats:italic> insertion. Among 7,324 MTB genomes from the NCBI database, 87 strains had mutations in the <jats:italic>mpt64<\/jats:italic> gene sequence, with four common mutation sites causing single amino acid changes, including G34A (8.0%), A103G (27.6%), T128A (9.2%), and C477A (24.1%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A negative MPT64 antigen result in MTB cultures can be attributed to mutations in the <jats:italic>mpt64<\/jats:italic> gene, and infections caused by these strains are more likely to be misdiagnosed.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1531853","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T14:26:22Z","timestamp":1740579982000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["mpt64 mutations in Mycobacterium tuberculosis with negative MPT64 antigen assay results from a tertiary hospital in Southeastern China"],"prefix":"10.3389","volume":"12","author":[{"given":"Xinling","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujuan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songjun","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,26]]},"reference":[{"key":"B1","year":"2023","journal-title":"Global Tuberculosis Report 2023. 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