{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:45:57Z","timestamp":1784828757520,"version":"3.55.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"crossref","award":["1S68722N"],"award-info":[{"award-number":["1S68722N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2024,1,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            While infections caused by\n            <jats:italic>Mycobacterium abscessus<\/jats:italic>\n            complex (MABC) are rising worldwide, the current treatment of these infections is far from ideal due to its numerous shortcomings thereby increasing the urge for novel drug targets. In this study, mycothione reductase (Mtr) was evaluated for its potential as a drug target for MABC infections since it is a key enzyme needed in the recycling of mycothiol, the main low-molecular-weight thiol protecting the bacteria against reactive oxygen species and other reactive intermediates. First, a\n            <jats:italic>Mab<\/jats:italic>\n            \u2206\n            <jats:italic>mtr<\/jats:italic>\n            mutant strain was generated, lacking\n            <jats:italic>mtr<\/jats:italic>\n            expression. Next, the\n            <jats:italic>in vitro<\/jats:italic>\n            sensitivity of\n            <jats:italic>Mab<\/jats:italic>\n            \u2206\n            <jats:italic>mtr<\/jats:italic>\n            to oxidative stress and antimycobacterial drugs was determined. Finally, we evaluated the intramacrophage survival and the virulence of\n            <jats:italic>Mab<\/jats:italic>\n            \u2206\n            <jats:italic>mtr<\/jats:italic>\n            in\n            <jats:italic>Galleria mellonella<\/jats:italic>\n            larvae.\n            <jats:italic>Mab<\/jats:italic>\n            \u2206\n            <jats:italic>mtr<\/jats:italic>\n            demonstrated a 39.5-fold reduction in IC90 when exposed to bedaquiline\n            <jats:italic>in vitro<\/jats:italic>\n            . Furthermore, the\n            <jats:italic>Mab<\/jats:italic>\n            \u2206\n            <jats:italic>mtr<\/jats:italic>\n            mutant showed a decreased ability to proliferate inside macrophages and larvae, suggesting that Mtr plays an important role during MABC infection. Altogether, these findings support the assumption of Mtr being a potential target for antimycobacterial drugs.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>Mycobacterium abscessus<\/jats:italic>\n              complex (MABC) is a group of bacteria causing a serious public health problem worldwide due to its ability to cause progressive disease, its highly resistant profile against various antibiotics, and its lengthy treatment. Therefore, new drugs are needed to alleviate antibiotic resistance and reduce the length of the current treatment. A potential new target for new antibiotics is mycothione reductase (Mtr), an important enzyme belonging to a pathway that protects the bacteria against harmful conditions. Our research created a bacterium deficient of\n              <jats:italic>mtr<\/jats:italic>\n              by using advanced genetic techniques and demonstrated that\n              <jats:italic>mtr<\/jats:italic>\n              -deficient bacteria have a decreased ability to multiply during infection. Furthermore, we show evidence that currently used antibiotics combined with\n              <jats:italic>mtr<\/jats:italic>\n              deficiency can lead to a better treatment of MABC infection. Altogether, our results validate Mtr as a potential new target and suggest that Mtr plays a role during MABC infection.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00669-23","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T14:37:25Z","timestamp":1702391845000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Mycothione reductase as a potential target in the fight against\n            <i>Mycobacterium abscessus<\/i>\n            infections"],"prefix":"10.1128","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1266-9513","authenticated-orcid":false,"given":"T.","family":"Piller","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"De Vooght","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Gansemans","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Van Nieuwerburgh","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4361-8911","authenticated-orcid":true,"given":"P.","family":"Cos","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.659997"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2020.05.028"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11101322"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3201\/2109.141634"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms10071454"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi5695"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27206948"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20122868"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2020.106148"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12984"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0098-2997(01)00010-3"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2022.07.013"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7074"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2013.11.004"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232315095"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep29491"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00128-18"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2019.7867"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01467-18"},{"key":"e_1_3_3_21_2","unstructured":"Andrews S. 2010. 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