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Among the other Mrr1\u2010regulated genes are putative methylglyoxal reductases. Methylglyoxal (MG) is a toxic metabolite that is elevated in diabetes, uremia, and sepsis, which are diseases that increase the risk for candidiasis, and MG serves as a regulatory signal in diverse organisms. Our studies in\n                    <jats:italic>Clavispora lusitaniae<\/jats:italic>\n                    , also known as\n                    <jats:italic>Candida lusitaniae<\/jats:italic>\n                    , showed that Mrr1 regulates expression of two paralogous MG reductases,\n                    <jats:italic>MGD1<\/jats:italic>\n                    and\n                    <jats:italic>MGD2<\/jats:italic>\n                    , and that both participate in MG resistance and MG catabolism. Exogenous MG increased Mrr1\u2010dependent expression of\n                    <jats:italic>MGD1<\/jats:italic>\n                    and\n                    <jats:italic>MGD2<\/jats:italic>\n                    as well as expression of\n                    <jats:italic>MDR1<\/jats:italic>\n                    , which encodes an efflux pump that exports fluconazole. MG improved growth in the presence of fluconazole and this was largely Mrr1\u2010dependent with contributions from a secondary transcription factor, Cap1. Increased fluconazole resistance was also observed in mutants lacking Glo1, a Mrr1\u2010independent MG catabolic enzyme. Isolates from other\n                    <jats:italic>Candida<\/jats:italic>\n                    species displayed heterogeneity in MG resistance and MG stimulation of azole resistance. We propose endogenous and host\u2010derived MG can induce\n                    <jats:italic>MDR1<\/jats:italic>\n                    and other Mrr1\u2010regulated genes causing increased drug resistance, which may contribute to some instances of fungal treatment failure.\n                  <\/jats:p>","DOI":"10.1111\/mmi.14604","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T12:41:08Z","timestamp":1608036068000},"page":"116-130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Mrr1 regulation of methylglyoxal catabolism and methylglyoxal\u2010induced fluconazole resistance in\n                    <i>Candida lusitaniae<\/i>"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0271-2346","authenticated-orcid":false,"given":"Amy R.","family":"Biermann","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Geisel 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