Cryptococcus neoformans senses CO2 through the carbonic anhydrase Can2 and the adenylyl cyclase Cac1

被引:123
作者
Mogensen, EG
Janbon, G
Chaloupka, J
Steegborn, C
Fu, MS
Moyrand, F
Klengel, T
Pearson, DS
Geeves, MA
Buck, J
Levin, LR
Mühlschlegel, FA
机构
[1] Univ Kent, Dept Biosci, Canterbury CT2 7NJ, Kent, England
[2] Inst Pasteur, CNRS, FRE2849, Unite Mycol Mol, F-75015 Paris, France
[3] Cornell Univ, Joan & Sanford Weill Med Coll 1, Dept Pharmacol, New York, NY 10021 USA
[4] Ruhr Univ Bochum, Dept Physiol Chem, D-44801 Bochum, Germany
基金
英国惠康基金;
关键词
D O I
10.1128/EC.5.1.103-111.2006
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Cryptococcus neoformans, a fungal pathogen of humans, causes fatal meningitis in immunocompromised patients. Its virulence is mainly determined by the elaboration of a polysaccharide capsule surrounding its cell wall. During its life, C. neoformans is confronted with and responds to dramatic variations in CO2 concentrations; one important morphological change triggered by the shift from its natural habitat (0.033% CO2) to infected hosts (5% CO2) is the induction of capsule biosynthesis. In cells, CO2 is hydrated to bicarbonate in a spontaneous reaction that is accelerated by carbonic anhydrases. Here we show that C. neoformans contains two beta-class carbonic anhydrases, Can1 and Can2. We further demonstrate that CAN2, but not CAN], is abundantly expressed and essential for the growth of C. neoformans in its natural environment, where CO2 concentrations are limiting. Structural studies reveal that Can2 forms a homodimer in solution. Our data reveal Can2 to be the main carbonic anhydrase and suggest a physiological role for bicarbonate during C. neoformans growth. Bicarbonate directly activates the C. neoformans Cac1 adenylyl cyclase required for capsule synthesis. We show that this specific activation is optimal at physiological pH.
引用
收藏
页码:103 / 111
页数:9
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