{"id":6621,"date":"2026-09-21T21:41:06","date_gmt":"2026-09-21T14:41:06","guid":{"rendered":"https:\/\/mkimia.fst.unair.ac.id\/uncovering-tuberculosis-resistance-behind-changes-in-the-pzase-enzyme\/"},"modified":"2026-09-21T21:57:22","modified_gmt":"2026-09-21T14:57:22","slug":"uncovering-tuberculosis-resistance-behind-changes-in-the-pzase-enzyme","status":"publish","type":"post","link":"https:\/\/mkimia.fst.unair.ac.id\/en\/uncovering-tuberculosis-resistance-behind-changes-in-the-pzase-enzyme\/","title":{"rendered":"Uncovering Tuberculosis Resistance Behind Changes in the PZase Enzyme"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-post\" data-elementor-id=\"6621\" class=\"elementor elementor-6621 elementor-6611\" data-elementor-post-type=\"post\">\n\t\t\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-3f1138c4 elementor-section-height-min-height elementor-section-items-top elementor-section-boxed elementor-section-height-default\" data-id=\"3f1138c4\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-wide\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-50 elementor-top-column elementor-element elementor-element-33104423\" data-id=\"33104423\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-7abedd8e elementor-widget elementor-widget-theme-post-title elementor-page-title elementor-widget-heading\" data-id=\"7abedd8e\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"theme-post-title.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h1 class=\"elementor-heading-title elementor-size-default\">Uncovering Tuberculosis Resistance Behind Changes in the PZase Enzyme<\/h1>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-60bcdb9b elementor-widget elementor-widget-post-info\" data-id=\"60bcdb9b\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"post-info.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<ul class=\"elementor-inline-items elementor-icon-list-items elementor-post-info\">\n\t\t\t\t\t\t\t\t<li class=\"elementor-icon-list-item elementor-repeater-item-734f236 elementor-inline-item\" itemprop=\"author\">\n\t\t\t\t\t\t<a href=\"https:\/\/mkimia.fst.unair.ac.id\/en\/author\/editormkimia\/\">\n\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-icon\">\n\t\t\t\t\t\t\t\t<svg aria-hidden=\"true\" class=\"e-font-icon-svg e-far-user-circle\" viewBox=\"0 0 496 512\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\"><path d=\"M248 104c-53 0-96 43-96 96s43 96 96 96 96-43 96-96-43-96-96-96zm0 144c-26.5 0-48-21.5-48-48s21.5-48 48-48 48 21.5 48 48-21.5 48-48 48zm0-240C111 8 0 119 0 256s111 248 248 248 248-111 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class=\"e-font-icon-svg e-fas-calendar\" viewBox=\"0 0 448 512\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\"><path d=\"M12 192h424c6.6 0 12 5.4 12 12v260c0 26.5-21.5 48-48 48H48c-26.5 0-48-21.5-48-48V204c0-6.6 5.4-12 12-12zm436-44v-36c0-26.5-21.5-48-48-48h-48V12c0-6.6-5.4-12-12-12h-40c-6.6 0-12 5.4-12 12v52H160V12c0-6.6-5.4-12-12-12h-40c-6.6 0-12 5.4-12 12v52H48C21.5 64 0 85.5 0 112v36c0 6.6 5.4 12 12 12h424c6.6 0 12-5.4 12-12z\"><\/path><\/svg>\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-text elementor-post-info__item elementor-post-info__item--type-date\">\n\t\t\t\t\t\t\t\t\t\t<time>September 21, 2026<\/time>\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t<\/a>\n\t\t\t\t<\/li>\n\t\t\t\t<\/ul>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-371cf975 elementor-widget elementor-widget-theme-post-featured-image elementor-widget-image\" data-id=\"371cf975\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"theme-post-featured-image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t\t\t<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img fetchpriority=\"high\" decoding=\"async\" width=\"1024\" height=\"576\" src=\"https:\/\/mkimia.fst.unair.ac.id\/wp-content\/uploads\/sites\/27\/2026\/04\/aip-general-1024x576-1.jpg\" class=\"attachment-full size-full wp-image-6102\" alt=\"\" srcset=\"https:\/\/mkimia.fst.unair.ac.id\/wp-content\/uploads\/sites\/27\/2026\/04\/aip-general-1024x576-1.jpg 1024w, https:\/\/mkimia.fst.unair.ac.id\/wp-content\/uploads\/sites\/27\/2026\/04\/aip-general-1024x576-1-300x169.jpg 300w, https:\/\/mkimia.fst.unair.ac.id\/wp-content\/uploads\/sites\/27\/2026\/04\/aip-general-1024x576-1-768x432.jpg 768w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">AIP Illustration (Photo: UNAIR NEWS)<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-623b747b elementor-widget elementor-widget-text-editor\" data-id=\"623b747b\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\tTuberculosis (TB) remains one of the infectious diseases that is difficult to control, particularly due to the emergence of drug-resistant <em>Mycobacterium tuberculosis<\/em>. One of the important drugs used in TB therapy is pyrazinamide (PZA), which requires the enzyme pyrazinamidase (PZase) to convert it into its active form. The PZase enzyme is encoded by the <em>pncA<\/em> gene; therefore, changes or mutations in this gene are thought to play an important role in the development of PZA resistance.<br><br>This study investigated the relationship between <em>pncA<\/em> gene mutations, PZase enzyme characteristics, and PZA resistance in two clinical isolates of <em>M. tuberculosis<\/em>, namely R1 and R2. Isolate R1 was resistant to PZA at a concentration of 100 \u03bcg\/mL, whereas R2 was resistant at 150 \u03bcg\/mL. Genetic analysis revealed that R1 harbored three <em>pncA<\/em> mutations resulting in the amino acid substitutions Cys14Arg, Arg140His, and Ser179Gly, while R2 carried four mutations resulting in the substitutions Ala26Ser, Ala38Pro, Thr135Pro, and Arg140His.<br><br>To determine the effects of these mutations on enzyme function, the <em>pncA<\/em> genes from both isolates were recombinantly expressed using <em>Escherichia coli<\/em>. The resulting mutant PZase proteins had a molecular mass of approximately 21 kDa and were subsequently analyzed for their catalytic activity. The results showed that the catalytic efficiency of PZase-R1 was 1.759 mM\u207b\u00b9\u00b7min\u207b\u00b9, whereas that of PZase-R2 was 1.500 mM\u207b\u00b9\u00b7min\u207b\u00b9. These values were lower than that of the normal PZase, which reached 2.443 mM\u207b\u00b9\u00b7min\u207b\u00b9.<br><br>The reductions in catalytic efficiency reached 28.0% for PZase-R1 and 38.6% for PZase-R2. These findings indicate that mutations in <em>pncA<\/em> not only alter the genetic sequence but may also affect the ability of the PZase enzyme to perform its function. The resulting reduction in enzyme activity is thought to contribute to the ability of <em>M. tuberculosis<\/em> to survive exposure to pyrazinamide.<br><br>Nevertheless, because each isolate carries multiple mutations simultaneously, further research is required to determine the contribution of each individual mutation to changes in PZase function and PZA resistance. Approaches such as <em>site-directed mutagenesis<\/em> and protein structure modeling may help elucidate how each amino acid substitution affects the enzyme&#8217;s structure and its interaction with the drug.<br><br>This study demonstrates that understanding TB resistance requires more than simply identifying mutations in DNA. Small changes in a gene can lead to changes in the corresponding protein, affect enzyme activity, and ultimately contribute to the ability of bacteria to survive drug exposure. Understanding the relationship between genes, enzymes, and drug resistance is expected to provide a foundation for developing improved resistance detection methods and more effective TB treatment strategies.<br><br><em><strong>Keywords<\/strong><\/em>: pyrazinamide resistance, <em>pncA<\/em> gene, mutant PZase, catalytic kinetics.<br><br><strong>Paper Link:<\/strong><br><br><strong>Purkan Purkan<\/strong>, Alivia Nadila, Bilqis Aliifa Nabilah, R Merlyn Sujatha, Wiwin Retnowati, Pratiwi Pudjiastuti, and Sofijan Hadi. <em>Kinetical Analysis of Mutant PZase Enzyme to Uncover the Pyrazinamide Resistance in Mycobacterium tuberculosis Clinical Isolates<\/em>. <em>New Microbiologica<\/em>, 2026, 49(2), 107\u2013116.<br><br><a href=\"https:\/\/newmicrobiologica.org\/wp-content\/uploads\/2026\/07\/MICRO_2_2026_2.1_FULL_496N570_Purkan-107-116.pdf\">https:\/\/newmicrobiologica.org\/wp-content\/uploads\/2026\/07\/MICRO_2_2026_2.1_FULL_496N570_Purkan-107-116.pdf<\/a><br><br><strong>Authors and Affiliations<\/strong><br><br><strong>Purkan Purkan\u00b9<\/strong>, Alivia Nadila\u00b9, Bilqis Aliifa Nabilah\u00b9, R Merlyn Sujatha\u00b3, Wiwin Retnowati\u2074, Pratiwi Pudjiastuti\u00b9, and Sofijan Hadi\u00b9<br><br>\u00b9 <em>Department of Chemistry, Faculty of Science and Technology, Airlangga University, Jl. Mulyorejo, Surabaya 60115, Indonesia.<\/em><br><br>\u00b2 <em>Research Group of Biochemical Engineering, Enzyme Biotechnology and Gene Cloning, Airlangga University, Jl. Mulyorejo, Surabaya 60115, Indonesia.<\/em><br><br>\u00b3 <em>Department of Biochemistry, St. Peter\u2019s Institute of Higher Education and Research, Avadi, Chennai, Tamil Nadu, India.<\/em><br><br>\u2074 <em>Microbiology Division, Faculty of Medicine, Airlangga University, Jl. Prof. Dr. Moestajab, Surabaya, Indonesia.<\/em><br><br><strong>Corresponding author:<\/strong> <a href=\"mailto:purkan@fst.unair.ac.id\">purkan@fst.unair.ac.id<\/a><br><br>&nbsp;<br><p class=\"isSelectedEnd\"><em>This article is republished from the Popular Scientific Articles section of Universitas Airlangga (UNAIR) and has been adapted for publication on the UNAIR Chemistry website.<\/em><\/p><br><em>Original source:<\/em> <em><a href=\"https:\/\/unair.ac.id\/mengungkap-resistensi-tuberkulosis-di-balik-perubahan-enzim-pzase-2\/\">&#8220;Uncovering Tuberculosis Resistance Behind Changes in the PZase Enzyme&#8221;<\/a><\/em>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-5051293\" data-id=\"5051293\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-5657a8f3 elementor-widget elementor-widget-heading\" data-id=\"5657a8f3\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h4 class=\"elementor-heading-title elementor-size-default\">Other news<\/h4>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-2e6167bc elementor-widget-divider--view-line elementor-widget elementor-widget-divider\" data-id=\"2e6167bc\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"divider.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-divider\">\n\t\t\t<span class=\"elementor-divider-separator\">\n\t\t\t\t\t\t<\/span>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>Tuberculosis (TB) remains one of the infectious diseases that is difficult to control, particularly due to the emergence of drug-resistant Mycobacterium tuberculosis. One of the important drugs used in TB [&hellip;]<\/p>\n","protected":false},"author":14,"featured_media":6102,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[30],"tags":[],"class_list":["post-6621","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Uncovering Tuberculosis Resistance Behind Changes in the PZase Enzyme - S2 Kimia Fakultas Sains dan Teknologi Universitas Airlangga<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/mkimia.fst.unair.ac.id\/en\/uncovering-tuberculosis-resistance-behind-changes-in-the-pzase-enzyme\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Uncovering Tuberculosis Resistance Behind Changes in the PZase Enzyme - S2 Kimia Fakultas Sains dan Teknologi Universitas Airlangga\" \/>\n<meta property=\"og:description\" content=\"Tuberculosis (TB) remains one of the infectious diseases that is difficult to control, particularly due to the emergence of drug-resistant Mycobacterium tuberculosis. 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