Calcineurin Orchestrates Hyphal Growth, Septation, Drug Resistance and Pathogenesis of Aspergillus fumigatus: Where Do We Go from Here?

被引:25
作者
Juvvadi, Praveen R. [1 ]
Steinbach, William J. [1 ,2 ]
机构
[1] Duke Univ, Med Ctr, Dept Pediat, Div Pediat Infect Dis, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA
关键词
Aspergillus fumigatus; calcineurin; hyphal growth; septation; virulence; FK506; cyclosporine A; phosphorylation; drug target; drug resistance;
D O I
10.3390/pathogens4040883
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Studies on fungal pathogens belonging to the ascomycota phylum are critical given the ubiquity and frequency with which these fungi cause infections in humans. Among these species, Aspergillus fumigatus causes invasive aspergillosis, a leading cause of death in immunocompromised patients. Fundamental to A. fumigatus pathogenesis is hyphal growth. However, the precise mechanisms underlying hyphal growth and virulence are poorly understood. Over the past 10 years, our research towards the identification of molecular targets responsible for hyphal growth, drug resistance and virulence led to the elucidation of calcineurin as a key signaling molecule governing these processes. In this review, we summarize our salient findings on the significance of calcineurin for hyphal growth and septation in A. fumigatus and propose future perspectives on exploiting this pathway for designing new fungal-specific therapeutics.
引用
收藏
页码:883 / 893
页数:11
相关论文
共 57 条
[1]   Response to Environmental Stresses, Cell-wall Integrity, and Virulence Are Orchestrated Through the Calcineurin Pathway in Ustilago hordei [J].
Antonio Cervantes-Chavez, Jose ;
Ali, Shawkat ;
Bakkeren, Guus .
MOLECULAR PLANT-MICROBE INTERACTIONS, 2011, 24 (02) :219-232
[2]   CALCINEURIN IS ESSENTIAL IN CYCLOSPORINE-A-SENSITIVE AND FK506-SENSITIVE YEAST STRAINS [J].
BREUDER, T ;
HEMENWAY, CS ;
MOVVA, NR ;
CARDENAS, ME ;
HEITMAN, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (12) :5372-5376
[3]   TARGETS OF IMMUNOPHILIN-IMMUNOSUPPRESSANT COMPLEXES ARE DISTINCT HIGHLY CONSERVED REGIONS OF CALCINEURIN-A [J].
CARDENAS, ME ;
MUIR, RS ;
BREUDER, T ;
HEITMAN, J .
EMBO JOURNAL, 1995, 14 (12) :2772-2783
[4]   On the roles of calcineurin in fungal growth and pathogenesis [J].
Chen Y.-L. ;
Kozubowski L. ;
Cardenas M.E. ;
Heitman J. .
Current Fungal Infection Reports, 2010, 4 (4) :244-255
[5]   Calcineurin is essential for survival during membrane stress in Candida albicans [J].
Cruz, MC ;
Goldstein, AL ;
Blankenship, JR ;
Del Poeta, M ;
Davis, D ;
Cardenas, ME ;
Perfect, JR ;
McCusker, JH ;
Heitman, J .
EMBO JOURNAL, 2002, 21 (04) :546-559
[6]   Calcineurin is required for hyphal elongation during mating and haploid fruiting in Cryptococcus neoformans [J].
Cruz, MC ;
Fox, DS ;
Heitman, J .
EMBO JOURNAL, 2001, 20 (05) :1020-1032
[7]   YEAST HAS HOMOLOGS (CNA1 AND CNA2 GENE-PRODUCTS) OF MAMMALIAN CALCINEURIN, A CALMODULIN-REGULATED PHOSPHOPROTEIN PHOSPHATASE [J].
CYERT, MS ;
KUNISAWA, R ;
KAIM, D ;
THORNER, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (16) :7376-7380
[8]   Calcineurin signaling in Saccharomyces cereviside:: how yeast go crazy in response to stress [J].
Cyert, MS .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 311 (04) :1143-1150
[9]   Functional characterization of the Aspergillus fumigatus calcineurin [J].
da Silva Ferreira, Marcia Eliana ;
Heinekamp, Thorsten ;
Haertl, Albert ;
Brakhage, Axel A. ;
Semighini, Camile P. ;
Harris, Steven D. ;
Savoldi, Marcela ;
de Gouvea, Paula Fagundes ;
de Souza Goldman, Maria Helena ;
Goldman, Gustavo H. .
FUNGAL GENETICS AND BIOLOGY, 2007, 44 (03) :219-230
[10]   Calcineurin Is an Antagonist to PKA Protein Phosphorylation Required for Postmating Filamentation and Virulence, While PP2A Is Required for Viability in Ustilago maydis [J].
Egan, John D. ;
Garcia-Pedrajas, Maria D. ;
Andrews, David L. ;
Gold, Scott E. .
MOLECULAR PLANT-MICROBE INTERACTIONS, 2009, 22 (10) :1293-1301