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 The Eng1 β-Glucanase EnhancesHistoplasmaVirulence by Reducing β-Glucan Exposure

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Andrew L. Garfoot ◽  
Qian Shen ◽  
Marcel Wüthrich ◽  
Bruce S. Klein ◽  
Chad A. Rappleye
Keyword(s):  
Cell Wall ◽  
Proinflammatory Cytokine ◽  
Histoplasma Capsulatum ◽  
Cytokine Production ◽  
Yeast Cells ◽  
Wall Structure ◽  
Cell Mediated Immunity ◽  
Proinflammatory Cytokine Production ◽  
Pathogenic Yeast

ABSTRACTThe fungal pathogenHistoplasma capsulatumparasitizes host phagocytes. To avoid antimicrobial immune responses,Histoplasmayeasts must minimize their detection by host receptors while simultaneously interacting with the phagocyte. PathogenicHistoplasmayeast cells, but not avirulent mycelial cells, secrete the Eng1 protein, which is a member of the glycosylhydrolase 81 (GH81) family. We show thatHistoplasmaEng1 is a glucanase that hydrolyzes β-(1,3)-glycosyl linkages but is not required forHistoplasmagrowthin vitroor for cell separation. However,Histoplasmayeasts lacking Eng1 function have attenuated virulencein vivo, particularly during the cell-mediated immunity stage.Histoplasmayeasts deficient for Eng1 show increased exposure of cell wall β-glucans, which results in enhanced binding to the Dectin-1 β-glucan receptor. Consistent with this, Eng1-deficient yeasts trigger increased tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) cytokine production from macrophages and dendritic cells. While not responsible for large-scale cell wall structure and function, the secreted Eng1 reduces levels of exposed β-glucans at the yeast cell wall, thereby diminishing potential recognition by Dectin-1 and proinflammatory cytokine production by phagocytes. In α-glucan-producingHistoplasmastrains, Eng1 acts in concert with α-glucan to minimize β-glucan exposure: α-glucan provides a masking function by covering the β-glucan-rich cell wall, while Eng1 removes any remaining exposed β-glucans. Thus,HistoplasmaEng1 has evolved a specialized pathogenesis function to remove exposed β-glucans, thereby enhancing the ability of yeasts to escape detection by host phagocytes.IMPORTANCEThe success ofHistoplasma capsulatumas an intracellular pathogen results, in part, from an ability to minimize its detection by receptors on phagocytic cells of the immune system. In this study, we showed thatHistoplasmapathogenic yeast cells, but not avirulent mycelia, secrete a β-glucanase, Eng1, which reduces recognition of fungal cell wall β-glucans. We demonstrated that the Eng1 β-glucanase promotesHistoplasmavirulence by reducing levels of surface-exposed β-glucans on yeast cells, thereby enablingHistoplasmayeasts to escape detection by the host β-glucan receptor, Dectin-1. As a consequence, phagocyte recognition ofHistoplasmayeasts is reduced, leading to less proinflammatory cytokine production by phagocytes and less control ofHistoplasmainfectionin vivo. Thus,Histoplasmayeasts express two mechanisms to avoid phagocyte detection: masking of cell wall β-glucans by α-glucan and enzymatic removal of exposed β-glucans by the Eng1 β-glucanase.

scholarly journals Contribution of Candida albicans Cell Wall Components to Recognition by and Escape from Murine Macrophages

2010 ◽  
Vol 78 (4) ◽  
pp. 1650-1658 ◽  
Author(s):  
C. G. J. McKenzie ◽  
U. Koser ◽  
L. E. Lewis ◽  
J. M. Bain ◽  
H. M. Mora-Montes ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Cell Wall Protein ◽  
Host Immune System ◽  
Wild Type ◽  
Human Fungal Pathogen ◽  
Protein Mutants ◽  
Hyphal Formation ◽  
Type Strains ◽  
Macrophage Uptake

ABSTRACT The pathogenicity of the opportunistic human fungal pathogen Candida albicans depends on its ability to escape destruction by the host immune system. Using mutant strains that are defective in cell surface glycosylation, cell wall protein synthesis, and yeast-hypha morphogenesis, we have investigated three important aspects of C. albicans innate immune interactions: phagocytosis by primary macrophages and macrophage cell lines, hyphal formation within macrophage phagosomes, and the ability to escape from and kill macrophages. We show that cell wall glycosylation is critically important for the recognition and ingestion of C. albicans by macrophages. Phagocytosis was significantly reduced for mutants deficient in phosphomannan biosynthesis (mmn4Δ, pmr1Δ, and mnt3 mnt5Δ), whereas O- and N-linked mannan defects (mnt1Δ mnt2Δ and mns1Δ) were associated with increased ingestion, compared to the parent wild-type strains and genetically complemented controls. In contrast, macrophage uptake of mutants deficient in cell wall proteins such as adhesins (ece1Δ, hwp1Δ, and als3Δ) and yeast-locked mutants (clb2Δ, hgc1Δ, cph1Δ, efg1Δ, and efg1Δ cph1Δ), was similar to that observed for wild-type C. albicans. Killing of macrophages was abrogated in hypha-deficient strains, significantly reduced in all glycosylation mutants, and comparable to wild type in cell wall protein mutants. The diminished ability of glycosylation mutants to kill macrophages was not a consequence of impaired hyphal formation within macrophage phagosomes. Therefore, cell wall composition and the ability to undergo yeast-hypha morphogenesis are critical determinants of the macrophage's ability to ingest and process C. albicans.

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

Spilanthol as a promising antifungal alkylamide for the treatment of vulvovaginal candidiasis

2021 ◽  
Author(s):  
Rodrigo L Fabri ◽  
Jhamine C O Freitas ◽  
Ari S O Lemos ◽  
Lara M Campos ◽  
Irley O M Diniz ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Cell Membrane ◽  
Multidrug Resistant ◽  
Fungal Strain ◽  
Vulvovaginal Candidiasis ◽  
Biofilm Matrix

Abstract Spilanthol is a bioactive alkylamide from the native Amazon plant species, Acmella oleracea. However, antifungal activities of spilanthol and its application to the therapeutic treatment of candidiasis remains to be explored. This study sought to evaluate the in vitro and in vivo antifungal activity of spilanthol previously isolated from A. oleracea (spilanthol(AcO)) against Candida albicans ATCC® 10231™, a multidrug-resistant fungal strain. Microdilution methods were used to determine inhibitory and fungicidal concentrations of spilanthol(AcO). In planktonic cultures, the fungal growth kinetics, yeast cell metabolic activity, cell membrane permeability and cell wall integrity were investigated. The effect of spilanthol(AcO) on the proliferation and adhesion of fungal biofilms was evaluated by whole slide imaging and scanning electron microscopy. The biochemical composition of the biofilm matrix was also analyzed. In parallel, spilanthol(AcO) was tested in vivo in an experimental vulvovaginal candidiasis model. Our in vitro analyses in C. albicans planktonic cultures detected a significant inhibitory effect of spilanthol(AcO), which affects both yeast cell membrane and cell wall integrity, interfering with the fungus growth. C. albicans biofilm proliferation and adhesion, as well as, carbohydrates and DNA in biofilm matrix were reduced after spilanthol(AcO) treatment. Moreover, infected rats treated with spilanthol(AcO) showed consistent reduction of both fungal burden and inflammatory processes compared to the untreated animals. Altogether, our findings demonstrated that spilanthol(AcO) is an bioactive compound against planktonic and biofilm forms of a multidrug resistant C. albicans strain. Furthermore, spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans. Lay Abstract This study sought to evaluate the antifungal activity of spilanthol against Candida albicans ATCC® 10 231™, a multidrug-resistant fungal strain. Our findings demonstrated that spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans.

scholarly journals Rapid in vivo development of resistance to daptomycin in vancomycin-resistant Enterococcus faecium due to genomic rearrangements

2021 ◽  
Author(s):  
Sarah Mollerup ◽  
Christine Elmeskov ◽  
Heidi Gumpert ◽  
Mette Pinholt ◽  
Tobias Steen Sejersen ◽  
...  
Keyword(s):  
Cell Wall ◽  
Enterococcus Faecium ◽  
Chromosomal Rearrangements ◽  
Resistance Mechanisms ◽  
Resistant Isolate ◽  
Wall Structure ◽  
Whole Genome ◽  
Cyclic Lipopeptide ◽  
Vancomycin Resistant

AbstractBackgroundDaptomycin is a cyclic lipopeptide used in the treatment of vancomycin-resistant Enterococcus faecium (VREfm). However, the development of daptomycin-resistant VREfm challenges the treatment of nosocomial VREfm infections. Resistance mechanisms of daptomycin are not fully understood. Here we analysed the genomic changes leading to a daptomycin-susceptible VREfm isolate becoming resistant after 40 days of daptomycin and linezolid combination therapy.MethodsThe two isogenic VREfm isolates (daptomycin-susceptible and daptomycin-resistant) were analysed using whole genome sequencing with Illumina and Nanopore.ResultsWhole genome comparative analysis identified the loss of a 46.5 kb fragment and duplication of a 29.7 kb fragment in the daptomycin-resistant isolate, with many implicated genes involved in cell wall synthesis. Two plasmids of the daptomycin-susceptible isolate were also found integrated in the chromosome of the resistant isolate. One nonsynonymous SNP in the rpoC gene was identified in the daptomycin-resistant isolate.ConclusionsDaptomycin resistance developed through chromosomal rearrangements leading to altered cell wall structure. Such novel types of resistance mechanisms can only be identified by comparing closed genomes of isogenic isolates.

scholarly journals Effect of β-1,6-Glucan Inhibitors on the Invasion Process of Candida albicans: Potential Mechanism of Their In Vivo Efficacy

2009 ◽  
Vol 53 (9) ◽  
pp. 3963-3971 ◽  
Author(s):  
Akihiro Kitamura ◽  
Saito Higuchi ◽  
Masato Hata ◽  
Katsuhiro Kawakami ◽  
Kumi Yoshida ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Critical Role ◽  
Vaginal Candidiasis ◽  
Specific Cell ◽  
Cell Wall Proteins ◽  
Invasion Process ◽  
In Vivo Efficacy

ABSTRACT β-1,6-Glucan is a fungus-specific cell wall component that is essential for the retention of many cell wall proteins. We recently reported the discovery of a small molecule inhibitor of β-1,6-glucan biosynthesis in yeasts. In the course of our study of its derivatives, we found a unique feature in their antifungal profile. D21-6076, one of these compounds, exhibited potent in vitro and in vivo antifungal activities against Candida glabrata. Interestingly, although it only weakly reduced the growth of Candida albicans in conventional media, it significantly prolonged the survival of mice infected by the pathogen. Biochemical evaluation of D21-6076 indicated that it inhibited β-1,6-glucan synthesis of C. albicans, leading the cell wall proteins, which play a critical role in its virulence, to be released from the cell. Correspondingly, adhesion of C. albicans cells to mammalian cells and their hyphal elongation were strongly reduced by the drug treatment. The results of the experiment using an in vitro model of vaginal candidiasis showed that D21-6076 strongly inhibited the invasion process of C. albicans without a significant reduction in its growth in the medium. These evidences suggested that D21-6076 probably exhibited in vivo efficacy against C. albicans by inhibiting its invasion process.

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