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Macrophage surface receptors bind to specific components of the\n                    <jats:italic>Candida<\/jats:italic>\n                    cell wall. Following phagocytosis,\n                    <jats:italic>Candida<\/jats:italic>\n                    can respond to the host's intracellular environment by switching from a yeast to a hyphal morphology facilitating escape from macrophages and allowing subsequent invasion of host tissues. Various disruptions of\n                    <jats:italic>Candida<\/jats:italic>\n                    's ability to form hyphae have been shown to reduce virulence and fitness in the host. Our previous work concluded that\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Candida albicans<\/jats:italic>\n                    <\/jats:styled-content>\n                    cells lacking AP\u20102 (\n                    <jats:italic>apm4\u0394\/\u0394)<\/jats:italic>\n                    , an endocytic adaptor complex, have increased cell wall chitin and morphologically defective hyphae in\u00a0vitro. Increased chitin has been correlated with decreased recognition by macrophages, possibly due to masking of cell wall \u03b2\u2010glucan, the target for the Dectin\u20101 immune receptor. Here we test the virulence profiles of\n                    <jats:italic>apm4\u0394\/\u0394<\/jats:italic>\n                    mutant, demonstrating a surprising increase in macrophage phagocytosis that does not occur due to the elevated exposure of \u03b2\u2010glucan, highlighting the importance of cell wall components beyond chitin and glucan for macrophage engagement and uptake. Furthermore, the\n                    <jats:italic>apm4<\/jats:italic>\n                    mutant exhibited parasitism of macrophages, surviving and proliferating within the phagosome, a phenotype that was then replicated with a well\u2010characterized yeast locked mutant, demonstrating the further complexity of\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">C.\u2009albicans<\/jats:styled-content>\n                      '\n                    <\/jats:italic>\n                    ability to evade macrophage responses. Finally, the combined phenotype of reduced hyphal formation but continued proliferation resulted in reduced virulence despite an equivalent burden of infection with wild\u2010type\n                    <jats:italic>Candida<\/jats:italic>\n                    infection, as determined using a zebrafish larval model of candidiasis.\n                  <\/jats:p>","DOI":"10.1111\/mmi.70032","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T06:31:02Z","timestamp":1762151462000},"page":"1-12","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>Candida albicans<\/i>\n                    Cells Lacking\n                    <scp>AP<\/scp>\n                    \u20102 Have Defective Hyphae and Are Avirulent Despite Increased Host Uptake and Intracellular Proliferation in Macrophages"],"prefix":"10.1111","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8287-788X","authenticated-orcid":false,"given":"Stella","family":"Christou","sequence":"first","affiliation":[{"name":"School of Biosciences University of Sheffield  Sheffield United\u00a0Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Evans","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health Florey Institute Bateson Centre University of Sheffield  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet","family":"Knafler","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Sheffield  Sheffield United\u00a0Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona Smaczynska\u2010de","family":"Rooij","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Sheffield  Sheffield United\u00a0Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn R.","family":"Ayscough","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Sheffield  Sheffield United\u00a0Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3429-9536","authenticated-orcid":false,"given":"Simon A.","family":"Johnston","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health Florey Institute Bateson Centre University of Sheffield  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01874-14"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep21489"},{"key":"e_1_2_8_4_1","unstructured":"Burgess T. B. F. R.Hammond P. T.Szkuta et\u00a0al.2023.\u201cCandida albicansSuppression of Neutrophil Reactive Nitrogen Species Is Rescued by Host Hif\u20101\u03b1 In\u00a0Vivo. bioRxiv.\u201dhttps:\/\/doi.org\/10.1101\/2023.11.02.565128v1."},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01612-14"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02535-18"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn304116f"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007597"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00989-09"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01452-08"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010389"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/523110"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00601-16"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof3040051"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-1140"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/1574\u20106968.12211"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02421-18"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80358-X"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.473223"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01282-10"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17625"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-407678-5.00004-0"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.17.4742"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1815"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.11.6813-6822.2001"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.2.298\u2010309.2005"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.01417\u201013"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02178-17"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008414"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00415-18"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof3030047"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens8010040"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1007"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00055-11"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003995"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01820-16"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01226-18"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.09.004"}],"container-title":["Molecular Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/mmi.70032","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T11:50:05Z","timestamp":1767441005000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/mmi.70032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,2]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/mmi.70032"],"URL":"https:\/\/doi.org\/10.1111\/mmi.70032","archive":["Portico"],"relation":{},"ISSN":["0950-382X","1365-2958"],"issn-type":[{"value":"0950-382X","type":"print"},{"value":"1365-2958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,2]]},"assertion":[{"value":"2024-03-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}