Discovering the secrets of the<i>Candida albicans</i>agglutinin-like sequence (ALS) gene family – a sticky pursuit

Hoyer, Lois L.; Green, Clayton B.; Oh, Soo Hee; Zhao, Xiaomin

doi:10.1080/13693780701435317

Cited by 310 publications

(334 citation statements)

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“…The peptide that we isolated is derived from a conserved region of two closely related members of the agglutinin-like sequence (ALS) gene family (27), which mediate adherence to and invasion of host cells (27,28). The capacity to invade host tissues is an important virulence determinant of C. albicans.…”

Section: Discussionmentioning

confidence: 99%

A Novel Th Cell Epitope of Candida albicans Mediates Protection from Fungal Infection

Bär

Gladiator

Bastidas

et al. 2012

The Journal of Immunology

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Fungal pathogens are a frequent cause of opportunistic infections. They live as commensals in healthy individuals but can cause disease when the immune status of the host is altered. T lymphocytes play a critical role in pathogen control. However, specific Ags determining the activation and function of antifungal T cells remain largely unknown. By using an immunoproteomic approach, we have identified for the first time, to our knowledge, a natural T cell epitope from Candida albicans. Isolation and sequencing of MHC class II-bound ligands from infected dendritic cells revealed a peptide that was recognized by a major population of all Candida-specific Th cells isolated from infected mice. Importantly, human Th cells also responded to stimulation with the peptide in an HLA-dependent manner but without restriction to any particular HLA class II allele. Immunization of mice with the peptide resulted in a population of epitope-specific Th cells that reacted not only with C. albicans but also with other clinically highly relevant species of Candida including the distantly related Candida glabrata. The extent of the reaction to different Candida species correlated with their degree of phylogenetic relationship to C. albicans. Finally, we show that the newly identified peptide acts as an efficient vaccine when used in combination with an adjuvant inducing IL-17A secretion from peptide-specific T cells. Immunized mice were protected from fatal candidiasis. Together, these results uncover a new immune determinant of the host response against Candida ssp. that could be exploited for the development of antifungal vaccines and immunotherapies.

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Section: Discussionmentioning

confidence: 99%

A Novel Th Cell Epitope of Candida albicans Mediates Protection from Fungal Infection

Bär

Gladiator

Bastidas

et al. 2012

The Journal of Immunology

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“…The ALS3 gene is a member of the C. albicans ALS (agglutinin-like sequence) gene family, which encodes eight cell surface glycoproteins with an N-terminal domain of adhesive function (Hoyer et al, 2008). The Als proteins diffusely cover the surface of the fungal cell, and therefore are involved in adherence to host and abiotic surfaces.…”

Section: Introductionmentioning

confidence: 99%

Staphylococcus aureus adherence to Candida albicans hyphae is mediated by the hyphal adhesin Als3p

et al. 2012

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The bacterium Staphylococcus (St.) aureus and the opportunistic fungus Candida albicans are currently among the leading nosocomial pathogens, often co-infecting critically ill patients, with high morbidity and mortality. Previous investigations have demonstrated preferential adherence of St. aureus to C. albicans hyphae during mixed biofilm growth. In this study, we aimed to characterize the mechanism behind this observed interaction. C. albicans adhesin-deficient mutant strains were screened by microscopy to identify the specific receptor on C. albicans hyphae recognized by St. aureus. Furthermore, an immunoassay was developed to validate and quantify staphylococcal binding to fungal biofilms. The findings from these experiments implicated the C. albicans adhesin agglutinin-like sequence 3 (Als3p) in playing a major role in the adherence process. This association was quantitatively established using atomic force microscopy, in which the adhesion force between single cells of the two species was significantly reduced for a C. albicans mutant strain lacking als3. Confocal microscopy further confirmed these observations, as St. aureus overlaid with a purified recombinant Als3 N-terminal domain fragment (rAls3p) exhibited robust binding. Importantly, a strain of Saccharomyces cerevisiae heterologously expressing Als3p was utilized to further confirm this adhesin as a receptor for St. aureus. Although the parental strain does not bind bacteria, expression of Als3p on the cell surface conferred upon the yeast the ability to strongly bind St. aureus. To elucidate the implications of these in vitro findings in a clinically relevant setting, an ex vivo murine model of co-infection was designed using murine tongue explants. Fluorescent microscopic images revealed extensive hyphal penetration of the epithelium typical of C. albicans mucosal infection. Interestingly, St. aureus bacterial cells were only seen within the Abbreviations: AFM, atomic force microscopy; CLSM, confocal laser scanning microscopy; ConA-Texas red, concanavalin A conjugated to Texas red; H&E, haematoxylin and eosin; IFA, indirect immunofluorescence; PNA-FISH, peptide nucleic acid probes for fluorescent in situ hybridization; SEM, scanning electron microscopy. A supplementary figure is available with the online version of this paper. Microbiology

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“…Mutaciones en estas adhesinas, se asocian a una importante disminución en la virulencia de C. albicans [5,6]. De estas proteínas Als3 es especialmente importante en adherencia [4].…”

Section: Introductionunclassified

Interacción Candida albicans-Hospedero: un proceso complejo en el que la inmunidad innata juega un importante papel

2013

Bol. Micol.

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Interacción Candida albicans-Hospedero: un proceso complejo en el que la inmunidad innata juega un importante papel (Candida albicans-host interaction: a complex process in which the innate immunity play an important role) Palabras clave: Candida, inmunidad innata, PRRs, PAMPS Key words: Candida, innate immunity, PRRs, PAMPS RESUMENCandida albicans es una levadura comensal, que bajo ciertas circunstancia puede convertirse en patógeno. La capacidad de cambiar se forma constituye un factor de virulencia, permitiéndole a la levadura invadir y diseminarse. El sistema inmune innato es capaz de reconocer las diferentes morfologías de C. albicans activando receptores (PRRs) que reconocen PAMPs o patrones moleculares conservados. Las células inmunes más importantes son los macrófagos y los neutrófilos que desencadenan una respuesta efectora a través de la fagocitosis y la activación de estrés oxidativo contra C. albicans. Las células dendríticas, por su parte expresan la mayoría de los PRRs involucrados en el reconocimiento de C. albicans activando la secreción de citoquinas hacia una respuesta tipo T H 1 (inducida por INF tipo1, IL-12, INFγ, ), T reg (inducida por TGFβ, IL-10) y TH 17 (inducida por IL-23, IL6). Las células epiteliales no sólo constituyen una barrera física frente a la infección por C. albicans, sino son fundamentales en el reconocimiento primario de este microorganismo. Mediante una respuesta bifásica estas células activan diferencialmente, vías de trans-ducción de señales que determinan que no se active una respuesta de citoquinas frente a la presencia de blastoconidios (forma comensal) y que se active frente a presencia de hifas (forma invasora). Por su parte,C. albicans es capaz de desarrollar mecanismos evasivos de la respuesta inmune. Esta compleja interacción y hongo-hospedero determina si el hospedero será capaz de eliminar a este microorganismo o si éste finalmente invadirá expresando su virulencia. ABSTRACTCandida albicans is a comensal microorganism that under certain circumstances is able to transform into a pathogen. This ability to switch constitute a virulence factor that C. albicans uses to invade and spread. The innate immune system recognize the different forms of C. albicans activating receptors (PRRs) that recognize PAMPs or conserved molecular patterns. The most impor tant immune cells are macrophages and neutrophils that generate an effector response through phagocytosis and oxidative burst against C. albicans. Dendritic cells express the most of PRRs involved in the recognition of C. albicans activating the cytokines synthesis forward to a T H 1 (induced by INF tipo1, IL-12, INFγ), T reg (induced by TGFβ, IL-10) y TH 17 (induced by IL-23, IL6) immune response. Epithelial cells not only constitute a physical barrier against C. albicans, but they are crucial in the first recognition of this microorganism. Through a biphasic response these cells differentially activate pathways that determine a no cytokine response when blastoconidia (commensal form) is present and an inflammatory ...

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Discovering the secrets of theCandida albicansagglutinin-like sequence (ALS) gene family – a sticky pursuit

Cited by 310 publications

References 83 publications

A Novel Th Cell Epitope of Candida albicans Mediates Protection from Fungal Infection

A Novel Th Cell Epitope of Candida albicans Mediates Protection from Fungal Infection

Staphylococcus aureus adherence to Candida albicans hyphae is mediated by the hyphal adhesin Als3p

Interacción Candida albicans-Hospedero: un proceso complejo en el que la inmunidad innata juega un importante papel

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