RRC ID 40068
著者 Bom VL, de Castro PA, Winkelströter LK, Marine M, Hori JI, Ramalho LN, dos Reis TF, Goldman MH, Brown NA, Rajendran R, Ramage G, Walker LA, Munro CA, Rocha MC, Malavazi I, Hagiwara D, Goldman GH.
タイトル The Aspergillus fumigatus sitA Phosphatase Homologue Is Important for Adhesion, Cell Wall Integrity, Biofilm Formation, and Virulence.
ジャーナル Eukaryot Cell
Abstract Aspergillus fumigatus is an opportunistic pathogenic fungus able to infect immunocompromised patients, eventually causing disseminated infections that are difficult to control and lead to high mortality rates. It is important to understand how the signaling pathways that regulate these factors involved in virulence are orchestrated. Protein phosphatases are central to numerous signal transduction pathways. Here, we characterize the A. fumigatus protein phosphatase 2A SitA, the Saccharomyces cerevisiae Sit4p homologue. The sitA gene is not an essential gene, and we were able to construct an A. fumigatus null mutant. The ΔsitA strain had decreased MpkA phosphorylation levels, was more sensitive to cell wall-damaging agents, had increased β-(1,3)-glucan and chitin, was impaired in biofilm formation, and had decreased protein kinase C activity. The ΔsitA strain is more sensitive to several metals and ions, such as MnCl2, CaCl2, and LiCl, but it is more resistant to ZnSO4. The ΔsitA strain was avirulent in a murine model of invasive pulmonary aspergillosis and induces an augmented tumor necrosis factor alpha (TNF-α) response in mouse macrophages. These results stress the importance of A. fumigatus SitA as a possible modulator of PkcA/MpkA activity and its involvement in the cell wall integrity pathway.
巻・号 14(8)
ページ 728-44
公開日 2015-8-1
DOI 10.1128/EC.00008-15
PII EC.00008-15
PMID 25911225
PMC PMC4519751
MeSH Animals Aspergillus fumigatus / metabolism* Biofilms / growth & development* Cation Transport Proteins / metabolism* Cell Adhesion / physiology* Cell Wall / metabolism* Chitin / metabolism Disease Models, Animal Female Fungal Proteins / metabolism Invasive Pulmonary Aspergillosis / metabolism Invasive Pulmonary Aspergillosis / microbiology Lung Diseases, Fungal / metabolism Lung Diseases, Fungal / microbiology Macrophages / microbiology Mice Mice, Inbred BALB C Phosphoric Monoester Hydrolases / metabolism* Signal Transduction / physiology Tumor Necrosis Factor-alpha / metabolism Virulence / physiology*
IF 2.992
引用数 24
WOS 分野 MYCOLOGY MICROBIOLOGY
リソース情報
病原微生物