Molecular analysis of CaMnt1p, a mannosyl transferase important for adhesion and virulence of
            <i>Candida albicans</i>

Buurman, Ed T.; Westwater, Caroline; Hube, Bernhard; Brown, Alistair J. P.; Odds, Frank C.; Gow, Neil A. R.

doi:10.1073/pnas.95.13.7670

Cited by 129 publications

(134 citation statements)

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“…This could be because the targets of both proteins are different, and only the ones affected by KRE2 are involved in cell wall structure. Alternatively, it could be because in U. maydis, KRE2 is the enzyme primarily responsible for the addition of the second mannose, while KTR3 is involved in the addition of the third residue as has been suggested for C. albicans (Buurman et al, 1998). The fact that the deletion of genes from KRE2/MNT1 or MNN1 families does not affect pathogenesis suggests that PMT4 target proteins might only have one mannose residue added or that a single mannose is sufficient to confer to these proteins their proper tertiary structure required for functionality in the infection program.…”

Section: Effects Of Protein O-mannosylation On Cell Wall Integrity Anmentioning

confidence: 99%

“…These studies show that blocking access to glycoproteins with sugar group binding compounds, such as concanavalin A, interferes with the adhesive capacity of fungal cells (Buck and Andrews, 1999). Thus, current evidence suggests that protein glycosylation plays a key role in the adhesive properties of fungal cells (Buurman et al, 1998;Huang et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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TheO-Mannosyltransferase PMT4 Is Essential for Normal Appressorium Formation and Penetration inUstilago maydis

2009

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In Saccharomyces cerevisiae, the PMT, KRE2/MNT1, and MNN1 mannosyltransferase protein families catalyze the steps of the O-mannosylation pathway, sequentially adding mannoses to target proteins. We have identified members of all three families and analyzed their roles in pathogenesis of the maize smut fungus Ustilago maydis. Furthermore, we have shown that PMT4, one of the three PMT family members in U. maydis, is essential for tumor formation in Zea mays. Significantly, PMT4 seems to be required only for pathogenesis and is dispensable for other aspects of the U. maydis life cycle. We subsequently show that the deletion of pmt4 results in a strong reduction in the frequency of appressorium formation, with the few appressoria that do form lacking the capacity to penetrate the plant cuticle. Our findings suggest that the O-mannosylation pathway plays a key role in the posttranslational modification of proteins involved in the pathogenic development of U. maydis. The fact that PMT homologs are not found in plants may open new avenues for the development of fungal control strategies. Moreover, the discovery of a highly specific requirement for a single O-mannosyltransferase should aid in the identification of the proteins directly involved in fungal plant penetration, thus leading to a better understanding of plant-fungi interactions.

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Section: Effects Of Protein O-mannosylation On Cell Wall Integrity Anmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TheO-Mannosyltransferase PMT4 Is Essential for Normal Appressorium Formation and Penetration inUstilago maydis

2009

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“…Those studied include members of the PMT and MNT gene families, all of which act in O-glycosylation, and the studies have demonstrated the importance of O-glycans in virulence (19,(21)(22)(23)(24). Also, Mnn9p is involved in extension of the N-linked glycan outer chain and hence is required for normal cell wall composition (25).…”

mentioning

confidence: 99%

Candida albicans Pmr1p, a Secretory Pathway P-type Ca2+/Mn2+-ATPase, Is Required for Glycosylation and Virulence

Bates

MacCallum

Bertram

et al. 2005

Journal of Biological Chemistry

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The cell surface of Candida albicans is the immediate point of contact with the host. The outer layer of the cell wall is enriched in highly glycosylated mannoproteins that are implicated in many aspects of the host-fungus interaction. Glycosylation of cell wall proteins is initiated in the endoplasmic reticulum and then elaborated in the Golgi as the protein passes through the secretory pathway. Golgi-bound mannosyltransferases require Mn 2؉ as an essential cofactor. In Saccharomyces cerevisiae, the P-type ATPase Pmr1p transports Ca 2؉ and Mn 2؉ ions into the Golgi. To determine the effect of a gross defect in glycosylation on host-fungus interactions of C. albicans, we disrupted the PMR1 homolog, CaPMR1. This mutation would simultaneously inhibit many Golgi-located, Mn 2؉ -dependent mannosyltransferases. The Capmr1⌬ null mutant was viable in vitro and had no growth defect even on media containing low Ca 2؉ /Mn 2؉ ion concentrations. However, cells grown in these media progressively lost viability upon entering stationary phase. Phosphomannan was almost completely absent, and O-mannan was severely truncated in the null mutant. A defect in N-linked outer chain glycosylation was also apparent, demonstrated by the underglycosylation of surface acid phosphatase. Consistent with the glycosylation defect, the null mutant had a weakened cell wall, exemplified by hypersensitivity to Calcofluor white, Congo red, and hygromycin B and constitutive activation of the cell integrity pathway. In a murine model of systemic infection, the null mutant was severely attenuated in virulence. These results demonstrate the importance of glycosylation for cell wall structure and virulence of C. albicans.

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“…The O-linked oligosaccharides, attached to serine or threonine, consist of a linear chain of one to five ␣1,2-linked mannose residues (12)(13)(14) and are known to be required for full virulence (14). The process of N-glycosylation has been studied extensively in Saccharomyces cerevisiae.…”

mentioning

confidence: 99%

Outer Chain N-Glycans Are Required for Cell Wall Integrity and Virulence of Candida albicans

Bates

Hughes

Munro

et al. 2006

Journal of Biological Chemistry

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218

277

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The outer layer of the Candida albicans cell wall is enriched in highly glycosylated mannoproteins that are the immediate point of contact with the host and strongly influence the host-fungal interaction. N-Glycans are the major form of mannoprotein modification and consist of a core structure, common to all eukaryotes, that is further elaborated in the Golgi to form the highly branched outer chain that is characteristic of fungi. In yeasts, outer chain branching is initiated by the action of the ␣1,6-mannosyltransferase Och1p; therefore, we disrupted the C. albicans OCH1 homolog to determine the importance of outer chain N-glycans on the host-fungal interaction. Loss of CaOCH1 resulted in a temperature-sensitive growth defect and cellular aggregation. Outer chain elongation of N-glycans was absent in the null mutant, demonstrated by the lack of the ␣1,6-linked polymannose backbone and the underglycosylation of N-acetylglucosaminidase. A null mutant lacking OCH1 was hypersensitive to a range of cell wall perturbing agents and had a constitutively activated cell wall integrity pathway. These mutants had near normal growth rates in vitro but were attenuated in virulence in a murine model of systemic infection. However, tissue burdens for the Caoch1⌬ null mutant were similar to control strains with normal N-glycosylation, suggesting the host-fungal interaction was altered such that high burdens were tolerated. This demonstrates the importance of N-glycan outer chain epitopes to the host-fungal interaction and virulence.Candida albicans is a commensal organism carried by a significant proportion of healthy individuals. It is the most common opportunistic fungal pathogen of humans causing superficial infections of the mucosa and in the immunocompromised host life-threatening systemic infections (1-4). The cell wall is the immediate point of contact between fungus and host and plays an important role in adherence, antigenicity, and the modulation of the host immune response (5-9). The outer layer of the cell wall is enriched in highly glycosylated mannoproteins (10), and both the protein and carbohydrate components have been implicated in the host-fungal interaction (5, 6, 11). The study of glycosylation in C. albicans therefore has its own relevance in identifying the carbohydrate epitopes involved in pathogenesis.Cell surface mannoproteins contain both O-and N-linked oligosaccharides. The O-linked oligosaccharides, attached to serine or threonine, consist of a linear chain of one to five ␣1,2-linked mannose residues (12)(13)(14) and are known to be required for full virulence (14). The process of N-glycosylation has been studied extensively in Saccharomyces cerevisiae. N-Linked glycosylation is initiated in the endoplasmic reticulum with the transfer of the Glc 3 Man 9 GlcNAc 2 oligosaccharide precursor to the protein target (15, 16). The oligosaccharide precursor is then processed by endoplasmic reticulum-resident glucosidases and a mannosidase to yield the mature triantennary Man 8 GlcNAc 2 core (17). Outer chain ...

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Molecular analysis of CaMnt1p, a mannosyl transferase important for adhesion and virulence of Candida albicans

Cited by 129 publications

References 56 publications

TheO-Mannosyltransferase PMT4 Is Essential for Normal Appressorium Formation and Penetration inUstilago maydis

TheO-Mannosyltransferase PMT4 Is Essential for Normal Appressorium Formation and Penetration inUstilago maydis

Candida albicans Pmr1p, a Secretory Pathway P-type Ca2+/Mn2+-ATPase, Is Required for Glycosylation and Virulence

Outer Chain N-Glycans Are Required for Cell Wall Integrity and Virulence of Candida albicans

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