scholarly journals Genotypic and phenotypic portrait of Candida albicans clinical isolates colonizing the airways of patients with cystic fibrosis

2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Mayssa Gnaien ◽  
Aicha Kallel ◽  
Fatma Khalsi ◽  
Samia Hamouda ◽  
Hanen Smaoui ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Cell Wall ◽  
Candida Albicans ◽  
Sequence Type ◽  
Clinical Isolates ◽  
Wall Structure ◽  
Single Strain ◽  
Host Environment ◽  
Multiple Stress ◽  
Differential Ability

Candida albicans colonizes the respiratory tract of patients with Cystic Fibrosis (CF). It competes with CF-associated pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, and contributes to disease severity. We serially recovered 160 C. albicans clinical isolates over a period of 30 months from the sputum of 23 pediatric and 2 adult antifungal-naive CF patients at Children’s Hospital Tunis and characterized the genotype and phenotype of a subset of strains using multilocus sequence typing (MLST) and growth assays on multiple stress-, filamentous growth- and biofilm-inducing media. Out of 16 patients regularly sampled for at least 9 months, 8 and 4 were chronically and transiently colonized with C. albicans, respectively. MLST analyses of 56 strains originating from 15 patients indicated that each patient was colonized with a single strain, while 8 patients (53%) carried isolates from clade 4 known to be enriched with strains from Middle East-Africa. A subset of these isolates with the same sequence type and colonizing 3 unrelated patients displayed altered susceptibility to cell wall-perturbing agents, suggesting changes in cell wall structure/function during growth in the CF lung. We also observed differential ability to filament and/or form biofilms in a set of identical isolates from clade 10 sampled over a period of 9 months in a pediatric CF patient, suggesting alterations in phenotypes associated with virulence. Our findings will rely on future whole-genome sequencing analyses to identify polymorphisms that could explain the emergence of new traits in C. albicans strains thriving in the CF host environment.

scholarly journals Role of the Candida albicans MNN1 gene family in cell wall structure and virulence

2013 ◽  
Vol 6 (1) ◽  
Author(s):  
Steven Bates ◽  
Rebecca A Hall ◽  
Jill Cheetham ◽  
Mihai G Netea ◽  
Donna M MacCallum ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Gene Family ◽  
Cell Wall Structure ◽  
Wall Structure

scholarly journals The GPI-modified proteins Pga59 and Pga62 of Candida albicans are required for cell wall integrity

Microbiology ◽  
2009 ◽  
Vol 155 (6) ◽  
pp. 2004-2020 ◽  
Author(s):  
Emilia Moreno-Ruiz ◽  
Giuseppe Ortu ◽  
Piet W. J. de Groot ◽  
Fabien Cottier ◽  
Céline Loussert ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Fungal Pathogens ◽  
High Sensitivity ◽  
Wall Structure ◽  
Minor Role ◽  
Cell Wall Proteins ◽  
Calcofluor White ◽  
Fungal Cell ◽  
A Minor

The fungal cell wall is essential in maintaining cellular integrity and plays key roles in the interplay between fungal pathogens and their hosts. The PGA59 and PGA62 genes encode two short and related glycosylphosphatidylinositol-anchored cell wall proteins and their expression has been previously shown to be strongly upregulated when the human pathogen Candida albicans grows as biofilms. Using GFP fusion proteins, we have shown that Pga59 and Pga62 are cell-wall-located, N- and O-glycosylated proteins. The characterization of C. albicans pga59Δ/pga59Δ, pga62Δ/pga62Δ and pga59Δ/pga59Δ pga62Δ/pga62Δ mutants suggested a minor role of these two proteins in hyphal morphogenesis and that they are not critical to biofilm formation. Importantly, the sensitivity to different cell-wall-perturbing agents was altered in these mutants. In particular, simultaneous inactivation of PGA59 and PGA62 resulted in high sensitivity to Calcofluor white, Congo red and nikkomicin Z and in resistance to caspofungin. Furthermore, cell wall composition and observation by transmission electron microscopy indicated an altered cell wall structure in the mutant strains. Collectively, these data suggest that the cell wall proteins Pga59 and Pga62 contribute to cell wall stability and structure.

scholarly journals Serologic Response to Cell Wall Mannoproteins and Proteins of Candida albicans

1998 ◽  
Vol 11 (1) ◽  
pp. 121-141 ◽  
Author(s):  
José P. Martínez ◽  
M. Luisa Gil ◽  
José L. López-Ribot ◽  
W. LaJean Chaffin
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Antibody Response ◽  
Humoral Response ◽  
Binding Activity ◽  
Cell Wall Protein ◽  
Wall Structure ◽  
Cell Mediated Immunity ◽  
Host Immune System

SUMMARY The cell wall of Candida albicans not only is the structure in which many biological functions essential for the fungal cells reside but also is a significant source of candidal antigens. The major cell wall components that elicit a response from the host immune system are proteins and glycoproteins, the latter being predominantly mannoproteins. Both the carbohydrate and protein moieties are able to trigger immune responses. Although cell-mediated immunity is often considered to be the most important line of defense against candidiasis, cell wall protein and glycoprotein components also elicit a potent humoral response from the host that may include some protective antibodies. Proteins and glycoproteins exposed at the most external layers of the wall structure are involved in several types of interactions of fungal cells with the exocellular environment. Thus, coating of fungal cells with host antibodies has the potential to influence profoundly the host-parasite interaction by affecting antibody-mediated functions such as opsonin-enhanced phagocytosis and blocking the binding activity of fungal adhesins for host ligands. In this review, the various members of the protein and glycoprotein fraction of the C. albicans cell wall that elicit an antibody response in vivo are examined. Although a number of proteins have been shown to stimulate an antibody response, for some of these species the response is not universal. On the other hand, some of the studies demonstrate that certain cell wall antigens and anti-cell wall antibodies may be the basis for developing specific and sensitive serologic tests for the diagnosis of candidasis, particularly the disseminated form. In addition, recent studies have focused on the potential for antibodies to cell wall protein determinants to protect the host against infection. Hence, a better understanding of the humoral response to cell wall antigens of C. albicans may provide the basis for the development of (i) effective procedures for the serodiagnosis of disseminated candidiasis and (ii) novel prophylactic (vaccination) and therapeutic strategies for the management of this type of infection.

scholarly journals FsFKS1, the 1,3-β-Glucan Synthase from the Caspofungin-Resistant Fungus Fusarium solani

2006 ◽  
Vol 5 (7) ◽  
pp. 1036-1042 ◽  
Author(s):  
Young-sil Ha ◽  
Sarah F. Covert ◽  
Michelle Momany
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Fusarium Solani ◽  
Cell Walls ◽  
Clinical Isolates ◽  
Fungal Cell ◽  
Spore Viability ◽  
Glucan Synthase ◽  
Main Components ◽  
Sensitive Fungus

ABSTRACT The cell wall, a mesh of carbohydrates and proteins, shapes and protects the fungal cell. The enzyme responsible for the synthesis of one of the main components of the fungal wall, 1,3-β-glucan synthase, is targeted by the antifungal caspofungin acetate (CFA). Clinical isolates of Candida albicans and Aspergillus fumigatus are much more sensitive to CFA than clinical isolates of Fusarium species. To better understand CFA resistance in Fusarium species, we cloned and sequenced FsFKS1, which encodes the Fusarium solani f. sp. pisi β(1,3)-d-glucan synthase, used RNA interference to reduce its expression and complemented deletion of the essential fks gene of the CFA-sensitive fungus A. fumigatus with FsFKS1. Reduction of the FsFKS1 message in F. solani f. sp. pisi reduced spore viability and caused lysis of spores and hyphae, consistent with cell wall defects. Compensating for the loss of A. fumigatus fks1 with FsFKS1 caused only a modest increase in the tolerance of A. fumigatus for CFA. Our results suggest that FsFKS1 is required for the proper construction of F. solani cell walls and that the resistance of F. solani to CFA is at best only partially due to resistance of the FsFKS1 enzyme to this antifungal agent.

scholarly journals Mitochondrial Sorting and Assembly Machinery Subunit Sam37 in Candida albicans: Insight into the Roles of Mitochondria in Fitness, Cell Wall Integrity, and Virulence

2012 ◽  
Vol 11 (4) ◽  
pp. 532-544 ◽  
Author(s):  
Yue Qu ◽  
Branka Jelicic ◽  
Filomena Pettolino ◽  
Andrew Perry ◽  
Tricia L. Lo ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Mitochondrial Function ◽  
Drug Tolerance ◽  
Cell Wall Integrity ◽  
Mitochondrial Outer Membrane ◽  
Wall Structure ◽  
Content Type ◽  
Mitochondrial Functions ◽  
Insight Into

ABSTRACT Recent studies indicate that mitochondrial functions impinge on cell wall integrity, drug tolerance, and virulence of human fungal pathogens. However, the mechanistic aspects of these processes are poorly understood. We focused on the mitochondrial outer membrane SAM ( S orting and A ssembly M achinery) complex subunit Sam37 in Candida albicans . Inactivation of SAM37 in C. albicans leads to a large reduction in fitness, a phenotype not conserved with the model yeast Saccharomyces cerevisiae . Our data indicate that slow growth of the sam37ΔΔ mutant results from mitochondrial DNA loss, a new function for Sam37 in C. albicans , and from reduced activity of the essential SAM complex subunit Sam35. The sam37ΔΔ mutant was hypersensitive to drugs that target the cell wall and displayed altered cell wall structure, supporting a role for Sam37 in cell wall integrity in C. albicans . The sensitivity of the mutant to membrane-targeting antifungals was not significantly altered. The sam37ΔΔ mutant was avirulent in the mouse model, and bioinformatics showed that the fungal Sam37 proteins are distant from their animal counterparts and could thus represent potential drug targets. Our study provides the first direct evidence for a link between mitochondrial function and cell wall integrity in C. albicans and is further relevant for understanding mitochondrial function in fitness, antifungal drug tolerance, and virulence of this major pathogen. Beyond the relevance to fungal pathogenesis, this work also provides new insight into the mitochondrial and cellular roles of the SAM complex in fungi.

scholarly journals Hypoxia Promotes Immune Evasion by Triggering β-Glucan Masking on theCandida albicansCell Surface via Mitochondrial and cAMP-Protein Kinase A Signaling

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Arnab Pradhan ◽  
Gabriela M. Avelar ◽  
Judith M. Bain ◽  
Delma S. Childers ◽  
Daniel E. Larcombe ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Protein Kinase ◽  
Immune Evasion ◽  
Fungal Pathogen ◽  
Wall Structure ◽  
Adaptation To Hypoxia ◽  
Low Oxygen ◽  
Content Type ◽  
Kinase A

ABSTRACTOrganisms must adapt to changes in oxygen tension if they are to exploit the energetic benefits of reducing oxygen while minimizing the potentially damaging effects of oxidation. Consequently, organisms in all eukaryotic kingdoms display robust adaptation to hypoxia (low oxygen levels). This is particularly important for fungal pathogens that colonize hypoxic niches in the host. We show that adaptation to hypoxia in the major fungal pathogen of humansCandida albicansincludes changes in cell wall structure and reduced exposure, at the cell surface, of β-glucan, a key pathogen-associated molecular pattern (PAMP). This leads to reduced phagocytosis by murine bone marrow-derived macrophages and decreased production of IL-10, RANTES, and TNF-α by peripheral blood mononuclear cells, suggesting that hypoxia-induced β-glucan masking has a significant effect uponC. albicans-host interactions. We show that hypoxia-induced β-glucan masking is dependent upon both mitochondrial and cAMP-protein kinase A (PKA) signaling. The decrease in β-glucan exposure is blocked by mutations that affect mitochondrial functionality (goa1Δ andupc2Δ) or that decrease production of hydrogen peroxide in the inner membrane space (sod1Δ). Furthermore, β-glucan masking is enhanced by mutations that elevate mitochondrial reactive oxygen species (aox1Δ). The β-glucan masking defects displayed bygoa1Δ andupc2Δ cells are suppressed by exogenous dibutyryl-cAMP. Also, mutations that inactivate cAMP synthesis (cyr1Δ) or PKA (tpk1Δtpk2Δ) block the masking phenotype. Our data suggest thatC. albicansresponds to hypoxic niches by inducing β-glucan masking via a mitochondrial cAMP-PKA signaling pathway, thereby modulating local immune responses and promoting fungal colonization.IMPORTANCEAnimal, plant, and fungal cells occupy environments that impose changes in oxygen tension. Consequently, many species have evolved mechanisms that permit robust adaptation to these changes. The fungal pathogenCandida albicanscan colonize hypoxic (low oxygen) niches in its human host, such as the lower gastrointestinal tract and inflamed tissues, but to colonize its host, the fungus must also evade local immune defenses. We reveal, for the first time, a defined link between hypoxic adaptation and immune evasion inC. albicans. As this pathogen adapts to hypoxia, it undergoes changes in cell wall structure that include masking of β-glucan at its cell surface, and it becomes better able to evade phagocytosis by innate immune cells. We also define the signaling mechanisms that mediate hypoxia-induced β-glucan masking, showing that they are dependent on mitochondrial signaling and the cAMP-protein kinase pathway. Therefore, hypoxia appears to trigger immune evasion in this fungal pathogen.

Chemical and enzymatic changes in the cell walls of Candida albicans and Saccharomyces cerevisiae by scanning electron microscopy

1980 ◽  
Vol 26 (8) ◽  
pp. 965-970 ◽  
Author(s):  
Yvonne Koch ◽  
K. H. Rademacher
Keyword(s):  
Electron Microscopy ◽  
Saccharomyces Cerevisiae ◽  
Scanning Electron Microscopy ◽  
Cell Wall ◽  
Candida Albicans ◽  
Cell Walls ◽  
Wall Structure ◽  
Before And After ◽  
Enzymatic Changes ◽  
Scanning Electron

Candida albicans and Saccharomyces cerevisiae cells were examined by scanning electron microscopy before and after extraction of the mannans of the cell wall. The surfaces of control cells were smooth; after mannan extraction they were rough and showed erosions which were particularly striking within the area of the scars. Helicase digested irregular holes through the cell wall within 20 min; these increased in size during an additional 40 min of digestion. These holes were not localized in or on the bud scars, which remained intact even after the long digestion period. The results were used to construct a model for yeast cell wall structure.

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