Functional characterization of an Aspergillus fumigatus calcium transporter (PmcA) that is essential for fungal infection.
Functional characterization of an Aspergillus fumigatus calcium transporter (PmcA) that is essential for fungal infection.
复制标题
DOI：
10.1371/journal.pone.0037591
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Goldman GH
中科院分区：
文献类型：
--
作者：
Dinamarco TM;Freitas FZ;Almeida RS;Brown NA;dos Reis TF;Ramalho LN;Savoldi M;Goldman MH;Bertolini MC;Goldman GH
烟曲霉是哺乳动物的主要条件致病菌，也是主要的过敏原。Ca ~（2+）-钙调神经磷酸酶途径影响A.烟熏。在这里，我们研究了A.烟曲霉Ca+2-钙调磷酸酶途径，pmcA，-B和-C，它们编码钙转运蛋白。我们证明，CrzA可以直接控制mRNA积累的pmcA-C基因的启动子区结合。CrzA结合实验表明pmcA和pmcC基因上游的5′-CACAGCCAC-3′和5′-CCCTGCCCC-3′序列分别是可能的钙调神经磷酸酶依赖性反应元件（CDRE）样共有基序。构建了pmcA和-B的突变体和pmcC的条件突变体，证明pmcC是必需基因。ΔpmcA和ΔpmcB突变体对钙更敏感，对锰更耐受，环孢菌素能够调节这些突变体对这些盐的敏感性或耐受性，支持钙调神经磷酸酶与这些转运蛋白的功能之间的相互作用。在ΔcalA和ΔcrzA突变株中，pmcA-C基因降低了肺泡中的mRNA丰度。然而，只有A.烟曲霉ΔpmcA对侵袭性肺曲霉病小鼠模型无毒力。
Aspergillus fumigatus is a primary and opportunistic pathogen, as well as a major allergen, of mammals. The Ca+2-calcineurin pathway affects virulence, morphogenesis and antifungal drug action in A. fumigatus. Here, we investigated three components of the A. fumigatus Ca+2-calcineurin pathway, pmcA,-B, and -C, which encode calcium transporters. We demonstrated that CrzA can directly control the mRNA accumulation of the pmcA-C genes by binding to their promoter regions. CrzA-binding experiments suggested that the 5′-CACAGCCAC-3′ and 5′-CCCTGCCCC-3′ sequences upstream of pmcA and pmcC genes, respectively, are possible calcineurin-dependent response elements (CDREs)-like consensus motifs. Null mutants were constructed for pmcA and -B and a conditional mutant for pmcC demonstrating pmcC is an essential gene. The ΔpmcA and ΔpmcB mutants were more sensitive to calcium and resistant to manganese and cyclosporin was able to modulate the sensitivity or resistance of these mutants to these salts, supporting the interaction between calcineurin and the function of these transporters. The pmcA-C genes have decreased mRNA abundance into the alveoli in the ΔcalA and ΔcrzA mutant strains. However, only the A. fumigatus ΔpmcA was avirulent in the murine model of invasive pulmonary aspergillosis.
登录
查看更多内容
影响因子：
3
作者：
Findon, Helen;Calcagno-Pizarelli, Ana-Maria;Martinez, Jose L.;Spielvogel, Anja;Markina-Inarrairaegui, Ane;Indrakumar, Tanya;Ramos, Jose;Penalva, Miguel A.;Espeso, Eduardo A.;Arst, Herbert N., Jr.
通讯作者：
Arst, Herbert N., Jr.
影响因子：
--
作者：
Bowman, Barry J.;Draskovic, Marija;Bowman, Emma Jean
通讯作者：
Bowman, Emma Jean
影响因子：
--
作者：
Goldman, GH;Marques, ED;Goldman, MHS
通讯作者：
Goldman, MHS
DOI：
10.1083/jcb.124.3.351
发表时间：
1994-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cunningham KW;Fink GR
通讯作者：
Fink GR
影响因子：
4.1
作者：
Flipphi, M;Kocialkowska, J;Felenbok, B
通讯作者：
Felenbok, B