Antifungal and Antitumor Activities of a Monoclonal Antibody Directed Against a Stress Mannoprotein of Candida albicans

Omaetxebarria, Miren Josu; Moragues, Marı́a D.; Elguezabal, Natalia; Rodriguez-Alejandre, A.; Brena, Sonia; Schneider, J.; Polonelli, Luciano; Pontón, José

doi:10.2174/1566524054022521

Cited by 25 publications

(20 citation statements)

References 38 publications

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“…Interestingly, this monoclonal antibody also reduces C. albicans germination, is fungicidal, and protects mice from disseminated candidiasis (33,54). However, C7 binds to other antigens in addition to Als3, such as enolase and nucleoporin Nup88 (41). Also, other antibodies that bind only to Als3 do not inhibit germination or reduce C. albicans viability.…”

Section: Als3 Functionmentioning

confidence: 99%

Candida albicans Als3, a Multifunctional Adhesin and Invasin

2011

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2Candida albicans is part of the normal human flora, and it grows on mucosal surfaces in healthy individuals. In susceptible hosts, this organism can cause both mucosal and hematogenously disseminated disease. For C. albicans to persist in the host and induce disease, it must be able to adhere to biotic and abiotic surfaces, invade host cells, and obtain iron. The C. albicans hypha-specific surface protein Als3 is a member of the agglutininlike sequence (Als) family of proteins and is important in all of these processes. Functioning as an adhesin, Als3 mediates attachment to epithelial cells, endothelial cells, and extracellular matrix proteins. It also plays an important role in biofilm formation on prosthetic surfaces, both alone and in mixed infection with Streptococcus gordonii. Als3 is one of two known C. albicans invasins. It binds to host cell receptors such as E-cadherin and N-cadherin and thereby induces host cells to endocytose the organism. Als3 also binds to host cell ferritin and enables C. albicans to utilize this protein as a source of iron. Because of its multiple functions and its high expression level in vivo, Als3 is a promising target for vaccines that induce protective cell-mediated and antibody responses. This review will summarize the multiple functions of this interesting and multifunctional protein.Candida spp. are the fourth most common cause of nosocomial bloodstream infections, and Candida albicans accounts for approximately 50% of cases of candidemia (20,67). This organism also causes at least 80% of cases of oropharyngeal and vulvovaginal candidiasis (57, 66). The predominance of C. albicans as a cause of both hematogenously disseminated and mucosal disease suggests that this organism possesses unique virulence factors compared to other species of Candida. One such factor, which is present only in C. albicans, is Als3. This protein plays a key role in multiple processes that are necessary for the organism to colonize the host and cause disease. These processes include adherence to host cells, biofilm formation, host cell invasion, and iron acquisition. Moreover, because Als3 is highly expressed in vivo, it is a promising target for therapeutic antibody and vaccine development. This review will discuss Als3 structure and function, as well as its utility as a therapeutic target. GENETIC AND BIOCHEMICAL CHARACTERISTICS OF Als3The ALS gene family. Als3 is encoded by the ALS3 gene, which is a member of the agglutinin-like sequence (ALS) gene family (23). This family was discovered by Hoyer et al. (24) based on its similarity to Saccharomyces cerevisiae SAG1, which codes for ␣ agglutinin. The ALS gene family has eight members (ALS1 to ALS7 and ALS9) (Fig. 1). These genes encode cell surface proteins that are predicted to share the same overall structure (Fig. 2). At the N terminus is a signal peptide followed by a 300-amino-acid immunoglobulin-like domain and a 104-amino-acid threonine-rich domain that contains ␤-sheets (18,22,47,55). Most Als proteins have adhesin function (18,55,72), an...

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Section: Als3 Functionmentioning

confidence: 99%

Candida albicans Als3, a Multifunctional Adhesin and Invasin

2011

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“…Antibodies protect against C. albicans infections by several mechanisms, including opsonisation, neutralisation of extracellular virulence factors, inhibition of the Candida adherence to host tissue, inhibition of yeast-to-hypha transition, and direct fungicidal activity. [31][32][33] The Pmt4p constituents are present on fungal cell surfaces and are accessible to antibodies. Neutrophils are the main effector cells responsible for the defense against C. albicans infection.…”

Section: Discussionmentioning

confidence: 99%

Vaccination with Recombinant Non-transmembrane Domain of Protein Mannosyltransferase 4 Improves Survival during Murine Disseminated Candidiasis

Wang

Yan

et al. 2015

Biological & Pharmaceutical Bulletin

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Candida albicans is the most common cause of invasive fungal infections in humans. The C. albicans cell wall proteins play an important role in crucial host-fungus interactions and might be ideal vaccine targets to induce protective immune response in host. Meanwhile, protein that is specific to C. albicans is also an ideal target of vaccine. In this study, 11 proteins involving cell wall biosynthesis, yeast-to-hypha formation, or specific to C. albicans were chosen and were successfully cloned, purified and verified. The immune protection of vaccination with each recombinant protein respectively in preventing systemic candidiasis in BALB/c mice was assessed. The injection of rPmt4p vaccination significantly increased survival rate, decreased fungal burdens in the heart, liver, brain, and kidneys, and increased serum levels of both immunoglobulin G (IgG) and IgM against rPmt4p in the immunized mice. Histopathological assessment demonstrated that rPmt4p vaccination protected the tissue structure, and decreased the infiltration of inflammatory cells. Passive transfer of the rPmt4p immunized serum increased survival rate against murine systemic candidiasis and significantly reduced organ fungal burden. The immune serum enhanced mouse neutrophil killing activity by directly neutralizing rPmt4p effects in vitro. Levels of interleukin (IL)-4, IL-10, IL-12p70, IL-17A and tumor necrosis factor (TNF)-α in serum were higher in the immunized mice compared to those in the adjuvant control group. In conclusion, our results suggested that rPmt4p vaccination may be considered as a potential vaccine candidate against systemic candidiasis.

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“…Deficit of such effective tools of the first defense line, like AMP, the human organism should compensate by alternative mechanisms of resistance to fungal microflora: activation of phagocytal function and increase of specific immunoglobulines synthesis. Recently was found out that monoclonal antibodies Mab C7 obtained by C. albicans mannoprotein not only suppressed the adhesion of yeast cells to different surfaces, but had the direct candidacidal activity (Omaetxebarria et al, 2005). Earlier unknown mechanism of AMP induction in vagina was discovered: cathelicidine hCAP-18, contained at high concentrations, but in inert form in semen plasma, falling in vagina with low pH transformed in its active form (Sorensen et al, 2003).…”

Section: Antimicrobial Peptides As Factor Of Local Immunity In Vulvovmentioning

confidence: 99%

The New About Congenital Antimicrobial Defense of Some Epithelial Tissues – Vaginal Mucosa and Hair

Vera¹,

Ekaterina²,

Nune³

2012

A Search for Antibacterial Agents

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Antifungal and Antitumor Activities of a Monoclonal Antibody Directed Against a Stress Mannoprotein of Candida albicans

Cited by 25 publications

References 38 publications

Candida albicans Als3, a Multifunctional Adhesin and Invasin

Candida albicans Als3, a Multifunctional Adhesin and Invasin

Vaccination with Recombinant Non-transmembrane Domain of Protein Mannosyltransferase 4 Improves Survival during Murine Disseminated Candidiasis

The New About Congenital Antimicrobial Defense of Some Epithelial Tissues – Vaginal Mucosa and Hair

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