title: Role of Protein Glycosylation in Candida parapsilosis Cell Wall Integrity and Host Interaction.
abstract: Candida parapsilosis is an important, emerging opportunistic fungal pathogen. Highly mannosylated fungal cell wall proteins are initial contact points with host immune systems. In Candida albicans, Och1 is a Golgi α1,6-mannosyltransferase that plays a key role in the elaboration of the N-linked mannan outer chain. Here, we disrupted C. parapsilosis OCH1 to gain insights into the contribution of N-linked mannosylation to cell fitness and to interactions with immune cells. Loss of Och1 in C. parapsilosis resulted in cellular aggregation, failure of morphogenesis, enhanced susceptibility to cell wall perturbing agents and defects in wall composition. We removed the cell wall O-linked mannans by β-elimination, and assessed the relevance of mannans during interaction with human monocytes. Results indicated that O-linked mannans are important for IL-1β stimulation in a dectin-1 and TLR4-dependent pathway; whereas both, N- and O-linked mannans are equally important ligands for TNFα and IL-6 stimulation, but neither is involved in IL-10 production. Furthermore, mice infected with C. parapsilosis och1Δ null mutant cells had significantly lower fungal burdens compared to wild-type (WT)-challenged counterparts. Therefore, our data are the first to demonstrate that C. parapsilosis N- and O-linked mannans have different roles in host interactions than those reported for C. albicans.
authors.affiliation: Departamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato Guanajuato, Mexico.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pérez-García
authors.affiliation: Department of Microbiology, University of Szeged Szeged, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Csonka
authors.affiliation: Departamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato Guanajuato, Mexico.
authors.forename: Arturo
authors.initials: A
authors.lastname: Flores-Carreón
authors.affiliation: Departamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato Guanajuato, Mexico.
authors.forename: Eine
authors.initials: E
authors.lastname: Estrada-Mata
authors.affiliation: Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional Irapuato, Mexico.
authors.forename: Erika
authors.initials: E
authors.lastname: Mellado-Mojica
authors.affiliation: Department of Microbiology, University of Szeged Szeged, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Németh
authors.affiliation: Departamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato Guanajuato, Mexico.
authors.forename: Luz A
authors.initials: LA
authors.lastname: López-Ramírez
authors.affiliation: Department of Microbiology, University of Szeged Szeged, Hungary.
authors.forename: Renata
authors.initials: R
authors.lastname: Toth
authors.affiliation: Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional Irapuato, Mexico.
authors.forename: Mercedes G
authors.initials: MG
authors.lastname: López
authors.affiliation: Biological Research Centre, Hungarian Academy of Sciences Szeged, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Vizler
authors.affiliation: Biological Research Centre, Hungarian Academy of Sciences Szeged, Hungary.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Marton
authors.affiliation: Department of Microbiology, University of Szeged Szeged, Hungary.
authors.forename: Adél
authors.initials: A
authors.lastname: Tóth
authors.affiliation: Department of Medicine and Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, NY, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Nosanchuk
authors.affiliation: Department of Microbiology, University of Szeged Szeged, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Gácser
authors.affiliation: Departamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato Guanajuato, Mexico.
authors.forename: Héctor M
authors.initials: HM
authors.lastname: Mora-Montes
keywords: Candida parapsilosis; cell wall; host-fungus interplay; mannosylation pathway; mannosyltransferase; virulence