{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:42:36Z","timestamp":1790145756078,"version":"4.0.1"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"NSFC-Zhejiang Joint Fund | Basic Public Welfare Research Program of Zhejiang Province","award":["LGF20H010003"],"award-info":[{"award-number":["LGF20H010003"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Resistance to pyrazinamide (PZA) poses significant challenges to tuberculosis (TB) management, and prediction of susceptibility to PZA has been challenging. This study examined PZA resistance-associated gene mutations in 125 multidrug-resistant clinical isolates of\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      (MTB) from Wenzhou, China. Phenotypic drug-susceptibility testing (pDST) for PZA was performed on clinical isolates using the MGIT 960 system to accurately determine resistance. Subsequently, whole-genome sequencing (WGS) was conducted on the 125 isolates to identify genetic mutations linked to PZA resistance, focusing specifically on the\n                      <jats:italic toggle=\"yes\">pncA<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">rpsA<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">panD<\/jats:italic>\n                      genes. To provide a rapid diagnostic alternative to traditional methods, the MeltPro MTB\/PZA assay was also utilized to detect mutations in\n                      <jats:italic toggle=\"yes\">pncA<\/jats:italic>\n                      . pDST revealed a PZA resistance rate of 59.20%, with 29.41% observed in strains resistant only to isoniazid and rifampicin, 77.61% in pre-extensively drug-resistant TB (pre-XDR-TB), and 100% in extensively drug-resistant TB (XDR-TB). Among the isolates, WGS identified mutations primarily in the\n                      <jats:italic toggle=\"yes\">pncA<\/jats:italic>\n                      (64.00%) and\n                      <jats:italic toggle=\"yes\">rpsA<\/jats:italic>\n                      (6.40%), with\n                      <jats:italic toggle=\"yes\">panD<\/jats:italic>\n                      mutations not detected. PZA resistance was strongly associated with\n                      <jats:italic toggle=\"yes\">pncA<\/jats:italic>\n                      mutations, present in 97.30% of PZA-resistant strains. WGS demonstrated 97.30% sensitivity and 84.31% specificity compared to pDST, while MeltPro MTB\/PZA showed 91.89% sensitivity and 86.27% specificity. Compared to WGS, MeltPro MTB\/PZA showed 92.50% positive percent agreement and 97.78% negative percentage agreement, highlighting its diagnostic value. In conclusion, PZA resistance in multidrug-resistant tuberculosis (MDR-TB) is primarily due to\n                      <jats:italic toggle=\"yes\">pncA<\/jats:italic>\n                      mutations. MeltPro MTB\/PZA assay offers a reliable, rapid alternative for PZA resistance prediction, supporting timely treatment adaptations for improved TB patient care.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>This study underscores the pressing need for reliable diagnostic methods to address high PZA resistance rates in TB cases, particularly in MDR-TB strains. By confirming that pncA mutations are the principal drivers of PZA resistance, we highlight the diagnostic potential of the MeltPro MTB\/PZA assay as a rapid and effective alternative to conventional culture-based methods. Demonstrating sensitivity and specificity comparable to WGS and pDST, this assay offers a practical, accessible approach for timely PZA resistance prediction. It supports more tailored and effective MDR-TB treatment strategies, which are essential for optimizing patient care in both well-resourced and constrained settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02745-24","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T09:00:43Z","timestamp":1747904443000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Comprehensive evaluation of the MeltPro MTB\/PZA assay for prediction of pyrazinamide resistance in multidrug-resistant tuberculosis"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6700-6920","authenticated-orcid":false,"given":"Guiqing","family":"He","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Wenzhou Central Hospital, The Dingli Clinical College of Wenzhou Medical University","place":["Wenzhou, China"]},{"name":"Laboratory 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