scholarly journals Subtelomeric Silencing of the MTL3 Locus of Candida glabrata Requires yKu70, yKu80, and Rif1 Proteins

2010 ◽  
Vol 9 (10) ◽  
pp. 1602-1611 ◽  
Author(s):  
Candy Y. Ramírez-Zavaleta ◽  
Griselda E. Salas-Delgado ◽  
Alejandro De Las Peñas ◽  
Irene Castaño
Keyword(s):  
Mating Type ◽  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Sexual Cycle ◽  
Content Type ◽  
Internal Position ◽  
Cell Type Specific ◽  
Opportunistic Fungal Pathogen ◽  
Reported Data ◽  
Type Information

ABSTRACT Candida glabrata is a haploid opportunistic fungal pathogen that is phylogenetically related to Saccharomyces cerevisiae. Even though C. glabrata has no known sexual cycle, it contains, like S. cerevisiae, three mating type-like loci (MTL) called MTL1, MTL2, and MTL3, as well as most of the genes required for mating, meiosis, and sporulation. MTL1 is localized at an internal position on chromosome B and is thought to be the locus corresponding to the MAT locus in S. cerevisiae. MTL2 and MTL3 are localized close to two telomeres on different chromosomes (29.4 kb from Chr E-L and 10.5 kb from Chr B-L, respectively). By using URA3 reporter gene insertions at the three MTL loci, we found that in contrast to the case for S. cerevisiae, only MTL3 is subject to transcriptional silencing while MTL2 is transcriptionally active, and this is in agreement with previously reported data. We found that the silencing of MTL3 is nucleated primarily at the left telomere of chromosome B and spreads over 12 kb to MTL3, rather than nucleating at flanking, closely positioned cis-acting silencers, like those flanking HMR and HML of S. cerevisiae. Interestingly, the silencing of MTL3 absolutely requires the yKu70, yKu80, and Rif1 proteins, in sharp contrast to the silencing of the HM loci of S. cerevisiae. In addition, we found that several cell type-specific genes are expressed in C. glabrata regardless of the presence, or even absence, of mating type information at any of the MTL loci.

scholarly journals Multifactorial Role of Mitochondria in Echinocandin Tolerance Revealed by Transcriptome Analysis of Drug-Tolerant Cells

mBio ◽  
2021 ◽  
Author(s):  
Rocio Garcia-Rubio ◽  
Cristina Jimenez-Ortigosa ◽  
Lucius DeGregorio ◽  
Christopher Quinteros ◽  
Erika Shor ◽  
...  
Keyword(s):  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Clinical Failure ◽  
First Line ◽  
Content Type ◽  
First Line Therapy ◽  
Line Therapy ◽  
Resistant Strains ◽  
Opportunistic Fungal Pathogen

Echinocandin drugs are a first-line therapy to treat invasive candidiasis, which is a major source of morbidity and mortality worldwide. The opportunistic fungal pathogen Candida glabrata is a prominent bloodstream fungal pathogen, and it is notable for rapidly developing echinocandin-resistant strains associated with clinical failure.

scholarly journals Mating-Type-Specific and Nonspecific PAK Kinases Play Shared and Divergent Roles in Cryptococcus neoformans

2002 ◽  
Vol 1 (2) ◽  
pp. 257-272 ◽  
Author(s):  
Ping Wang ◽  
Connie B. Nichols ◽  
Klaus B. Lengeler ◽  
Maria E. Cardenas ◽  
Gary M. Cox ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Mating Type ◽  
Fungal Pathogen ◽  
Sexual Cycle ◽  
Type Locus ◽  
Serotype A ◽  
A Cells ◽  
Genes Encoding ◽  
Opportunistic Fungal Pathogen ◽  
Synthetically Lethal

ABSTRACT Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle involving fusion of haploid MATα and MATa cells. Virulence has been linked to the mating type, and MATα cells are more virulent than congenic MATa cells. To study the link between the mating type and virulence, we functionally analyzed three genes encoding homologs of the p21-activated protein kinase family: STE20α, STE20a, and PAK1. In contrast to the STE20 genes that were previously shown to be in the mating-type locus, the PAK1 gene is unlinked to the mating type. The STE20α, STE20a, and PAK1 genes were disrupted in serotype A and D strains of C. neoformans, revealing central but distinct roles in mating, differentiation, cytokinesis, and virulence. ste20α pak1 and ste20a pak1 double mutants were synthetically lethal, indicating that these related kinases share an essential function. In summary, our studies identify an association between the STE20α gene, the MATα locus, and virulence in a serotype A clinical isolate and provide evidence that PAK kinases function in a MAP kinase signaling cascade controlling the mating, differentiation, and virulence of this fungal pathogen.

scholarly journals Aspergillus fumigatus Acetate Utilization Impacts Virulence Traits and Pathogenicity

mBio ◽  
2021 ◽  
Author(s):  
Laure Nicolas Annick Ries ◽  
Patricia Alves de Castro ◽  
Lilian Pereira Silva ◽  
Clara Valero ◽  
Thaila Fernanda dos Reis ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Fungal Pathogen ◽  
Carbon Sources ◽  
Body Fluids ◽  
Peripheral Tissues ◽  
Content Type ◽  
Virulence Traits ◽  
Acetate Utilization ◽  
Opportunistic Fungal Pathogen

Aspergillus fumigatus is an opportunistic fungal pathogen in humans. During infection, A. fumigatus is predicted to use host carbon sources, such as acetate, present in body fluids and peripheral tissues, to sustain growth and promote colonization and invasion.

scholarly journals High-Throughput Nano-Biofilm Microarray for Antifungal Drug Discovery

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Anand Srinivasan ◽  
Kai P. Leung ◽  
Jose L. Lopez-Ribot ◽  
Anand K. Ramasubramanian
Keyword(s):  
Cell Culture ◽  
Candida Albicans ◽  
Drug Discovery ◽  
High Throughput ◽  
Fungal Pathogen ◽  
Microarray Platform ◽  
Microbial Cell ◽  
Content Type ◽  
Petri Dishes ◽  
Opportunistic Fungal Pathogen

ABSTRACT Micro- and nanoscale technologies have radically transformed biological research from genomics to tissue engineering, with the relative exception of microbial cell culture, which is still largely performed in microtiter plates and petri dishes. Here, we present nanoscale culture of the opportunistic fungal pathogen Candida albicans on a microarray platform. The microarray consists of 1,200 individual cultures of 30 nl of C. albicans biofilms (“nano-biofilms”) encapsulated in an inert alginate matrix. We demonstrate that these nano-biofilms are similar to conventional macroscopic biofilms in their morphological, architectural, growth, and phenotypic characteristics. We also demonstrate that the nano-biofilm microarray is a robust and efficient tool for accelerating the drug discovery process: (i) combinatorial screening against a collection of 28 antifungal compounds in the presence of immunosuppressant FK506 (tacrolimus) identified six drugs that showed synergistic antifungal activity, and (ii) screening against the NCI challenge set small-molecule library identified three heretofore-unknown hits. This cell-based microarray platform allows for miniaturization of microbial cell culture and is fully compatible with other high-throughput screening technologies. IMPORTANCE Microorganisms are typically still grown in petri dishes, test tubes, and Erlenmeyer flasks in spite of the latest advances in miniaturization that have benefitted other allied research fields, including genomics and proteomics. Culturing microorganisms in small scale can be particularly valuable in cutting down time, cost, and reagent usage. This paper describes the development, characterization, and application of nanoscale culture of an opportunistic fungal pathogen, Candida albicans. Despite a more than 2,000-fold reduction in volume, the growth characteristics and drug response profiles obtained from the nanoscale cultures were comparable to the industry standards. The platform also enabled rapid identification of new drug candidates that were effective against C. albicans biofilms, which are a major cause of mortality in hospital-acquired infections.

scholarly journals Identification of the Mating-Type (MAT) Locus That Controls Sexual Reproduction of Blastomyces dermatitidis

2012 ◽  
Vol 12 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Wenjun Li ◽  
Thomas D. Sullivan ◽  
Eric Walton ◽  
Anna Floyd Averette ◽  
Sharadha Sakthikumar ◽  
...  
Keyword(s):  
Sexual Reproduction ◽  
Mating Type ◽  
Genetic Recombination ◽  
Sexual Cycle ◽  
Blastomyces Dermatitidis ◽  
Comparative Genomic ◽  
Dimorphic Fungi ◽  
Content Type ◽  
Long Time ◽  
Northern United States

ABSTRACTBlastomyces dermatitidisis a dimorphic fungal pathogen that primarily causes blastomycosis in the midwestern and northern United States and Canada. While the genes controlling sexual development have been known for a long time, the genes controlling sexual reproduction ofB. dermatitidis(teleomorph,Ajellomyces dermatitidis) are unknown. We identified the mating-type (MAT) locus in theB. dermatitidisgenome by comparative genomic approaches. TheB. dermatitidis MATlocus resembles those of other dimorphic fungi, containing either an alpha-box (MAT1-1) or an HMG domain (MAT1-2) gene linked to theAPN2,SLA2, andCOX13genes. However, in some strains ofB. dermatitidis, theMATlocus harbors transposable elements (TEs) that make it unusually large compared to theMATlocus of other dimorphic fungi. Based on theMATlocus sequences ofB. dermatitidis, we designed specific primers for PCR determination of the mating type. TwoB. dermatitidisisolates of opposite mating types were cocultured on mating medium. Immature sexual structures were observed starting at 3 weeks of coculture, with coiled-hyphae-containing cleistothecia developing over the next 3 to 6 weeks. Genetic recombination was detected in potential progeny by mating-type determination, PCR-restriction fragment length polymorphism (PCR-RFLP), and random amplification of polymorphic DNA (RAPD) analyses, suggesting that a meiotic sexual cycle might have been completed. The F1 progeny were sexually fertile when tested with strains of the opposite mating type. Our studies provide a model for the evolution of theMATlocus in the dimorphic and closely related fungi and open the door to classic genetic analysis and studies on the possible roles of mating and mating type in infection and virulence.

scholarly journals Cell Wall Chitosan Is Necessary for Virulence in the Opportunistic Pathogen Cryptococcus neoformans

2011 ◽  
Vol 10 (9) ◽  
pp. 1264-1268 ◽  
Author(s):  
Lorina G. Baker ◽  
Charles A. Specht ◽  
Jennifer K. Lodge
Keyword(s):  
Cell Wall ◽  
Cryptococcus Neoformans ◽  
Fungal Pathogen ◽  
Slow Growth ◽  
Opportunistic Pathogen ◽  
Mammalian Host ◽  
Cell Integrity ◽  
Content Type ◽  
Opportunistic Fungal Pathogen ◽  
Chitin And Chitosan

ABSTRACTCryptococcus neoformansis an opportunistic fungal pathogen that causes meningoencephalitis. Its cell wall is composed of glucans, proteins, chitin, and chitosan. Multiple genetic approaches have defined a chitosan-deficient syndrome that includes slow growth and decreased cell integrity. Here we demonstrate chitosan is necessary for virulence and persistence in the mammalian host.

scholarly journals Ascorbic Acid Inhibition of Candida albicans Hsp90-Mediated Morphogenesis Occurs via the Transcriptional Regulator Upc2

2014 ◽  
Vol 13 (10) ◽  
pp. 1278-1289 ◽  
Author(s):  
Frédérique Van Hauwenhuyse ◽  
Alessandro Fiori ◽  
Patrick Van Dijck
Keyword(s):  
Ascorbic Acid ◽  
Candida Albicans ◽  
Fungal Pathogen ◽  
Transcriptional Regulator ◽  
Hsp90 Inhibitor ◽  
Ergosterol Biosynthesis ◽  
Content Type ◽  
Temperature Changes ◽  
Opportunistic Fungal Pathogen ◽  
Hsp90 Function

ABSTRACTMorphogenetic transitions of the opportunistic fungal pathogenCandida albicansare influenced by temperature changes, with induction of filamentation upon a shift from 30 to 37°C. Hsp90 was identified as a major repressor of an elongated cell morphology at low temperatures, as treatment with specific inhibitors of Hsp90 results in elongated growth forms at 30°C. Elongated growth resulting from a compromised Hsp90 is considered neither hyphal nor pseudohyphal growth. It has been reported that ascorbic acid (vitamin C) interferes with the yeast-to-hypha transition inC. albicans. In the present study, we show that ascorbic acid also antagonizes the morphogenetic change caused by hampered Hsp90 function. Further analysis revealed that Upc2, a transcriptional regulator of genes involved in ergosterol biosynthesis, and Erg11, the target of azole antifungals, whose expression is in turn regulated by Upc2, are required for this antagonism. Ergosterol levels correlate with elongated growth and are reduced in cells treated with the Hsp90 inhibitor geldanamycin (GdA) and restored by cotreatment with ascorbic acid. In addition, we show that Upc2 appears to be required for ascorbic acid-mediated inhibition of the antifungal activity of fluconazole. These results identify Upc2 as a major regulator of ascorbic acid-induced effects inC. albicansand suggest an association between ergosterol content and elongated growth upon Hsp90 compromise.

scholarly journals Opportunistic fungal pathogen Candida glabrata circulates between humans and yellow-legged gulls

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Mohammed Hashim Al-Yasiri ◽  
Anne-Cécile Normand ◽  
Coralie L’Ollivier ◽  
Laurence Lachaud ◽  
Nathalie Bourgeois ◽  
...  
Keyword(s):  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Opportunistic Fungal Pathogen
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