Candida albicans Filamentation Does Not Require the cAMP-PKA Pathway In Vivo.
Candida albicans Filamentation Does Not Require the cAMP-PKA Pathway In Vivo.
复制标题
作者：
白色念珠菌是人类最常见的真菌病原体之一。它在发芽酵母和丝状形态(伪菌丝和菌丝)之间的转换能力与其发病密切相关。基于体外研究，cAMP-蛋白激酶A(PKA)途径是白念珠菌形态发生的关键调节因子。使用活体成像方法，我们研究了cAMP-PKA途径在感染过程中的作用。与它们在体外的作用一致，cAMP-PKA途径的下游效应器Efg1和Nrg1分别作为体内丝状化的激活器和抑制器发挥作用。令人惊讶的是，缺乏腺酰环化酶的菌株Cyr1在体内只显示出轻微的丝状化，尽管在37℃的Rpmi + 10%血清中完全不能丝状化。与这些发现一致的是，PKA催化亚基(Tpk1和Tpk2)的缺失，无论是单独还是联合，产生的菌株也在体内形成了丝状化，但在体外没有。从耳和肾组织分离的白色念珠菌的体内转录图谱显示，一组184个环境响应基因的表达与体外丝状(R2，0.62至0.68)基因有很好的相关性。这种一致性表明，体内和体外的转录反应相似，但上游调控机制是不同的。因此，这些数据强调，白色念珠菌的丝状化是一种复杂的表型，通过复杂的不同调控机制网络在不同的环境中发生。
Candida albicans is one of the most prevalent human fungal pathogens. Its ability to transition between budding yeast and filamentous morphological forms (pseudohyphae and hyphae) is tightly associated with its pathogenesis. Based on in vitro studies, the cAMP-protein kinase A (PKA) pathway is a key regulator of C. albicans morphogenesis. Using an intravital imaging approach, we investigated the role of the cAMP-PKA pathway during infection. Consistent with their roles in vitro, the downstream effectors of the cAMP-PKA pathway Efg1 and Nrg1 function, respectively, as an activator and a repressor of in vivo filamentation. Surprisingly, strains lacking the adenylyl cyclase, CYR1, showed only slightly reduced filamentation in vivo despite being completely unable to filament in RPMI + 10% serum at 37°C. Consistent with these findings, deletion of the catalytic subunits of PKA (Tpk1 and Tpk2), either singly or in combination, generated strains that also filamented in vivo but not in vitro. In vivo transcription profiling of C. albicans isolated from both ear and kidney tissue showed that the expression of a set of 184 environmentally responsive genes correlated well with in vitro filamentation (R2, 0.62 to 0.68) genes. This concordance suggests that the in vivo and in vitro transcriptional responses are similar but that the upstream regulatory mechanisms are distinct. As such, these data emphatically emphasize that C. albicans filamentation is a complex phenotype that occurs in different environments through an intricate network of distinct regulatory mechanisms.
登录
查看更多内容
影响因子：
9.8
作者：
Xu, Wenjie;Solis, Norma V.;Mitchell, Aaron P.
通讯作者：
Mitchell, Aaron P.
通过表型、转录组和磷酸蛋白质组分析揭示白色念珠菌 PKA 催化亚基无效突变体中 cAMP/PKA 通路的全局调节作用
影响因子：
3.6
作者：
Cao, Chengjun;Wu, Mei;Huang, Guanghua
通讯作者：
Huang, Guanghua
影响因子：
4.8
作者：
Huang MY;Mitchell AP
通讯作者：
Mitchell AP
影响因子：
4.5
作者：
Homann OR;Dea J;Noble SM;Johnson AD
通讯作者：
Johnson AD
影响因子：
6.7
作者：
Min K;Jannace TF;Si H;Veeramah KR;Haley JD;Konopka JB
通讯作者：
Konopka JB