{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T00:46:38Z","timestamp":1768610798376,"version":"3.49.0"},"reference-count":39,"publisher":"Microbiology Society","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science Foundation Ireland","award":["19\/FFP\/6642"],"award-info":[{"award-number":["19\/FFP\/6642"]}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","award":["R01DE030130"],"award-info":[{"award-number":["R01DE030130"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SPP2225"],"award-info":[{"award-number":["SPP2225"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,16]]},"abstract":"<jats:p>\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    uniquely possesses an expanded family of genes (the\n                    <jats:italic>TLO<\/jats:italic>\n                    gene family) that encodes 10\u201315 paralogues of the Med2 component of the transcriptional regulator Mediator. Previous studies have shown that\n                    <jats:italic>TLO<\/jats:italic>\n                    null mutants are unable to form hyphae and are hypersensitive to environmental stress. However, the reason for the\n                    <jats:italic>TLO<\/jats:italic>\n                    gene expansion remains unclear, and the current study aimed to determine if reduction in the\n                    <jats:italic>TLO<\/jats:italic>\n                    family copy number affected virulence. In order to investigate this, we used CRISPR-Cas9 mutagenesis to generate two\n                    <jats:italic>TLO<\/jats:italic>\n                    -depleted mutants: one mutant retaining only\n                    <jats:italic>TLO<\/jats:italic>\n                    \u03b2\n                    <jats:italic>2<\/jats:italic>\n                    (CaTLO2) and the second mutant containing only\n                    <jats:italic>TLO<\/jats:italic>\n                    \u03b3\n                    <jats:italic>5<\/jats:italic>\n                    (CaTLO5). Both\n                    <jats:italic>TLO<\/jats:italic>\n                    -depleted mutants exhibited increased filamentous growth, increased susceptibility to specific stresses and reduced virulence in a murine model of oropharyngeal candidiasis (OPC).\n                    <jats:italic>In vitro<\/jats:italic>\n                    , the CaTLO5 mutant also exhibited impaired hyphal escape from macrophages and reduced hyphal invasion of oral keratinocytes. We then investigated if complementation with\n                    <jats:italic>TLO<\/jats:italic>\n                    \u03b1\n                    <jats:italic>1<\/jats:italic>\n                    , a gene previously shown to restore wild-type growth in a \u0394\n                    <jats:italic>tlo<\/jats:italic>\n                    null mutant, could restore virulence.\n                    <jats:italic>In vitro<\/jats:italic>\n                    infection models showed that\n                    <jats:italic>TLO<\/jats:italic>\n                    \u03b1\n                    <jats:italic>1<\/jats:italic>\n                    could restore true hypha formation, epithelial invasion and hyphal escape from macrophages in the CaTLO5 background. The murine OPC model showed that\n                    <jats:italic>TLO<\/jats:italic>\n                    \u03b1\n                    <jats:italic>1<\/jats:italic>\n                    could restore wild-type virulence in both CaTLO2 and CaTLO5 strains, suggesting an essential role for \u03b1-\n                    <jats:italic>TLO<\/jats:italic>\n                    in oral mucosal infection. Together, these findings highlight the functional specialization between the \u03b1, \u03b2 and \u03b3\n                    <jats:italic>TLO<\/jats:italic>\n                    gene groups and establish \u03b1-\n                    <jats:italic>TLO<\/jats:italic>\n                    as a major regulator of virulence in\n                    <jats:italic>C. albicans<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1099\/mic.0.001654","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T15:16:41Z","timestamp":1768576601000},"source":"Crossref","is-referenced-by-count":0,"title":["Depletion of the Candida albicans TLO gene family reveals a requirement for alpha TLO genes for wild-type virulence"],"prefix":"10.1099","volume":"172","author":[{"given":"James","family":"O\u2019Connor-Moneley","sequence":"first","affiliation":[{"name":"Division of Oral Biosciences, Dublin Dental University Hospital & University of Dublin, Trinity College Dublin, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Lange","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute (HKI), Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter R.","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Division of Oral Biosciences, Dublin Dental University Hospital & University of Dublin, Trinity College Dublin, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sascha","family":"Brunke","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute (HKI), Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute (HKI), Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rishabh","family":"Sharma","sequence":"additional","affiliation":[{"name":"Oral Microbiome Research Laboratory, Kornberg School of Dentistry, Temple University, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumant","family":"Puri","sequence":"additional","affiliation":[{"name":"Oral Microbiome Research Laboratory, Kornberg School of Dentistry, Temple University, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard","family":"Hube","sequence":"additional","affiliation":[{"name":"Cluster of Excellence Balance of the Microverse, Jena, Germany"},{"name":"Institute of Microbiology, Friedrich Schiller University, Jena, Germany"},{"name":"Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute (HKI), Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek J.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Division of Oral Biosciences, Dublin Dental University Hospital & University of Dublin, Trinity College Dublin, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0469-1788","authenticated-orcid":false,"given":"Gary P.","family":"Moran","sequence":"additional","affiliation":[{"name":"Division of Oral Biosciences, Dublin Dental University Hospital & University of Dublin, Trinity College Dublin, Dublin, 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