Functional regions of Candida albicans hyphal cell wall protein Als3 that determine interaction with the oral bacterium Streptococcus gordonii

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.

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Cell wall protein mannosylation determines Candida albicans cell surface hydrophobicity

Microbiology ◽

10.1099/00221287-143-9-3015 ◽

1997 ◽

Vol 143 (9) ◽

pp. 3015-3021 ◽

Cited By ~ 64

Author(s):

J. Masuoka ◽

K. C. Hazen

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Cell Surface ◽

Cell Surface Hydrophobicity ◽

Surface Hydrophobicity ◽

Cell Wall Protein

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The Adhesin Hwp1 and the First Daughter Cell Localize to the a/a Portion of the Conjugation Bridge duringCandida albicansMating

Molecular Biology of the Cell ◽

10.1091/mbc.e03-04-0264 ◽

2003 ◽

Vol 14 (12) ◽

pp. 4920-4930 ◽

Cited By ~ 34

Author(s):

Karla J. Daniels ◽

Shawn R. Lockhart ◽

Janet F. Staab ◽

Paula Sundstrom ◽

David R. Soll

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Mating Type ◽

Daughter Cell ◽

Cell Wall Protein ◽

Parent Cell ◽

A Cells ◽

Α Pheromone

The cell wall protein Hwp1 was originally demonstrated to be expressed exclusively in hyphae of Candida albicans and cross-linked to human epithelium by mammalian transglutaminase. Hwp1 is expressed on the walls of hyphae formed by a/α, a/a, and α/α cells. Hence, it is expressed on hyphae independently of mating type. However, Hwp1 is selectively expressed on the wall of conjugation tubes formed by a/a cells, but not α/α cells, in the mating process. This was demonstrated in all possible crosses between four unrelated natural a/a strains and four unrelated α/α strains. In zygotes, Hwp1 is restricted to that portion of the wall of the conjugation bridge contributed by the a/a parent cell. Hwp1 staining further revealed that the first daughter bud that emerges from the conjugation bridge does so from the a/a-contributed portion. Hwp1 expression and localization during the mating process is, therefore, mating type specific, opaque phase specific, and α-pheromone induced. These results indicate that the mating type-specific contributions to the conjugation bridge during the mating process in C. albicans are qualitatively and functionally distinct and that the a/a portion of the bridge, which selectively contains Hwp1, bears the first daughter cell in the mating process.

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Characterization of Hwp2, a Candida albicans putative GPI-anchored cell wall protein necessary for invasive growth

Microbiological Research ◽

10.1016/j.micres.2009.03.006 ◽

2010 ◽

Vol 165 (3) ◽

pp. 250-258 ◽

Cited By ~ 16

Author(s):

Peter Hayek ◽

Leila Dib ◽

Pascal Yazbeck ◽

Berna Beyrouthy ◽

Roy A. Khalaf

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Cell Wall Protein ◽

Invasive Growth

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Characterisation of Pga1, a putative Candida albicans cell wall protein necessary for proper adhesion and biofilm formation

Mycoses ◽

10.1111/j.1439-0507.2010.01883.x ◽

2010 ◽

Vol 54 (6) ◽

pp. 491-500 ◽

Cited By ~ 19

Author(s):

Rami Hashash ◽

Samer Younes ◽

Wael Bahnan ◽

Joseph El Koussa ◽

Katia Maalouf ◽

...

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Biofilm Formation ◽

Cell Wall Protein

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

Infection and Immunity ◽

10.1128/iai.00001-10 ◽

2010 ◽

Vol 78 (4) ◽

pp. 1650-1658 ◽

Cited By ~ 164

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.

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