{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:56:40Z","timestamp":1790812600351,"version":"4.1.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Macrophages provide the first-line defense against invasive fungal infections and, therefore, escape from macrophage becomes the basis for the establishment of<jats:italic>Candida albicans<\/jats:italic>invasive infection. Here, we found that deletion of<jats:italic>ATP2<\/jats:italic>(<jats:italic>atp2<\/jats:italic>\u0394\/\u0394) in<jats:italic>C. albicans<\/jats:italic>resulted in a dramatic decrease from 69.2% (WT) to 1.2% in the escape rate<jats:italic>in vitro<\/jats:italic>. The effect of<jats:italic>ATP2<\/jats:italic>on macrophage clearance stands out among the genes currently known to affect clearance. In the normal mice, the<jats:italic>atp2<\/jats:italic>\u0394\/\u0394 cells were undetectable in major organs 72\u00a0h after systemic infection, while WT cells persisted<jats:italic>in vivo<\/jats:italic>. However, in the macrophage-depleted mice,<jats:italic>atp2<\/jats:italic>\u0394\/\u0394 could persist for 72\u00a0h at an amount comparable to that at 24\u00a0h. Regarding the mechanism, WT cells sustained growth and switched to hyphal form, which was more conducive to escape from macrophages, in media that mimic the glucose-deficient environment in macrophages. In contrast,<jats:italic>atp2<\/jats:italic>\u0394\/\u0394 cells can remained viable but were unable to complete morphogenesis in these media, resulting in them being trapped within macrophages in the yeast form. Meanwhile,<jats:italic>atp2<\/jats:italic>\u0394\/\u0394 cells were killed by oxidative stress in alternative carbon sources by 2- to 3-fold more than WT cells. Taken together,<jats:italic>ATP2<\/jats:italic>deletion prevents<jats:italic>C. albicans<\/jats:italic>from escaping macrophage clearance, and therefore<jats:italic>ATP2<\/jats:italic>has a functional basis as a drug target that interferes with macrophage clearance.<\/jats:p>","DOI":"10.3389\/fcimb.2021.643121","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T17:37:28Z","timestamp":1618594648000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Deletion of the ATP2 Gene in Candida albicans Blocks Its Escape From Macrophage Clearance"],"prefix":"10.3389","volume":"11","author":[{"given":"Yishan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanyan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanpeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuixiu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luobei","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1126\/science.1106753","article-title":"A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis","volume":"307","author":"Andries","year":"2005","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.mib.2020.05.007","article-title":"I want to break free - macrophage strategies to recognize and kill Candida albicans, and fungal counter-strategies to escape","volume":"58","author":"Austermeier","year":"2020","journal-title":"Curr. 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