Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, United States.
Curr Opin Microbiol. 2011 Dec;14(6):682-6. doi: 10.1016/j.mib.2011.09.014. Epub 2011 Oct 17.
In the healthy individual, Candida albicans is frequently found as a harmless commensal residing in the gastrointestinal tract. However, in the compromised patient, C. albicans may invade the body and cause disease that is associated with poor prognosis and high mortality. The C. albicans adenylyl cyclase, Cyr1, which is required for virulence in animal models, regulates three developmental programs, including invasive filamentous growth, phenotypic switching to a mating-competent cell type, and biofilm formation. Evidence suggests that Cyr1 controls these phenotypes in response to various environmental cues that are present within microbial populations. Additionally, C. albicans secretes an autoregulatory molecule, farnesol, which was recently shown to directly inhibit Cyr1 activity. Below, we summarize recent advances in our understanding of Cyr1-regulated development and discuss the multiple inputs known to positively and negatively regulate cAMP synthesis. We discuss the possibility that Cyr1 acts as a coincidence detector that tightly regulates fungal development in response to parallel environmental stimuli, and highlight ways in which this might occur.
在健康个体中，白色念珠菌常作为一种无害的共生体存在于胃肠道中。然而，在免疫功能受损的患者中，白色念珠菌可能会入侵人体并导致疾病，这些疾病与预后不良和高死亡率相关。白色念珠菌的腺苷酸环化酶 Cyr1 在动物模型中是毒力所必需的，它调节三个发育程序，包括侵袭丝状生长、表型转换为有交配能力的细胞类型和生物膜形成。有证据表明，Cyr1 控制这些表型是对微生物群体中存在的各种环境线索的反应。此外，白色念珠菌分泌一种自调节分子法尼醇，最近的研究表明它可以直接抑制 Cyr1 的活性。在下面，我们总结了我们对 Cyr1 调节的发育的理解的最新进展，并讨论了已知的正向和负向调节 cAMP 合成的多种输入。我们讨论了 Cyr1 作为一个巧合探测器的可能性，它可以紧密调节真菌对平行环境刺激的发育，并强调了可能发生的方式。
