title: Disruption of Protein Mannosylation AffectsCandida guilliermondiiCell Wall, Immune Sensing, and Virulence.
abstract: The fungal cell wall contains glycoproteins that interact with the host immune system. In the prominent pathogenic yeastCandida albicans, Pmr1 acts as a Golgi-resident ion pump that provides cofactors to mannosyltransferases, regulating the synthesis of mannans attached to glycoproteins. To gain insight into a putative conservation of such a crucial process within opportunistic yeasts, we were particularly interested in studying the role of thePMR1homolog in a low-virulent species that rarely causes candidiasis,Candida guilliermondii. We disruptedC. guilliermondii PMR1and found that loss of Pmr1 affected cell growth and morphology, biofilm formation, susceptibility to cell wall perturbing agents, mannan levels, and the wall composition and organization. Despite the significant increment in the amount of β1,3-glucan exposed at the wall surface, this positively influenced only the ability of the mutant to stimulate IL-10 production by human monocytes, suggesting that recognition of both mannan and β1,3-glucan, is required to stimulate strong levels of pro-inflammatory cytokines. Accordingly, our results indicateC. guilliermondiisensing by monocytes was critically dependent on the recognition ofN-linked mannans and β1,3-glucan, as reported in otherCandidaspecies. In addition, chemical remotion of cell wallO-linked mannans was found to positively influence the recognition ofC. guilliermondiiby human monocytes, suggesting thatO-linked mannans mask other cell wall components from immune cells. This observation contrasts with that reported inC. albicans. Finally, mice infected withC. guilliermondii pmr1Δ null mutant cells had significantly lower fungal burdens compared to animals challenged with the parental strain. Accordingly, the null mutant showed inability to kill larvae in theGalleria mellonellainfection model. This study thus demonstrates that mannans are relevant for theC. guilliermondii-host interaction, with an atypical role forO-linked mannans.
authors.affiliation: División de Ciencias Naturales y Exactas, Departamento de Biología, Universidad de Guanajuato Guanajuato, Mexico.
authors.forename: María J
authors.initials: MJ
authors.lastname: Navarro-Arias
authors.affiliation: Biomolécules et Biotechnologies Végétales, Université François-Rabelais de ToursTours, France; Groupe d'Etude des Interactions Hôte-Pathogène, Université d'AngersAngers, France.
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Defosse
authors.affiliation: Laboratoire de Microbiologie Fondamentale et Pathogénicité, Université Bordeaux 2, UMR-Centre National de la Recherche Scientifique 5234 Bordeaux, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Dementhon
authors.affiliation: Department of Microbiology, University of Szeged Szeged, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Csonka
authors.affiliation: Centro de Investigaciones y de Estudios Avanzados del Instituto Politécnico Nacional (IPN) Guanajuato, Mexico.
authors.forename: Erika
authors.initials: E
authors.lastname: Mellado-Mojica
authors.affiliation: Departamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina Londrina, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Dias Valério
authors.affiliation: División de Ciencias Naturales y Exactas, Departamento de Biología, Universidad de Guanajuato Guanajuato, Mexico.
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: González-Hernández
authors.affiliation: Biomolécules et Biotechnologies Végétales, Université François-Rabelais de Tours Tours, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Courdavault
authors.affiliation: Biomolécules et Biotechnologies Végétales, Université François-Rabelais de Tours Tours, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Clastre
authors.affiliation: División de Ciencias Naturales y Exactas, Departamento de Biología, Universidad de Guanajuato Guanajuato, Mexico.
authors.forename: Nahúm V
authors.initials: NV
authors.lastname: Hernández
authors.affiliation: División de Ciencias Naturales y Exactas, Departamento de Biología, 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: Dhirendra K
authors.initials: DK
authors.lastname: Singh
authors.affiliation: Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences Szeged, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Vizler
authors.affiliation: Department of Microbiology, University of Szeged Szeged, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Gácser
authors.affiliation: Departamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina Londrina, Brazil.
authors.forename: Ricardo S
authors.initials: RS
authors.lastname: Almeida
authors.affiliation: Laboratoire de Microbiologie Fondamentale et Pathogénicité, Université Bordeaux 2, UMR-Centre National de la Recherche Scientifique 5234 Bordeaux, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Noël
authors.affiliation: Centro de Investigaciones y de Estudios Avanzados del Instituto Politécnico Nacional (IPN) Guanajuato, Mexico.
authors.forename: Mercedes G
authors.initials: MG
authors.lastname: López
authors.affiliation: Groupe d'Etude des Interactions Hôte-Pathogène, Université d'Angers Angers, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Papon
authors.affiliation: División de Ciencias Naturales y Exactas, Departamento de Biología, Universidad de Guanajuato Guanajuato, Mexico.
authors.forename: Héctor M
authors.initials: HM
authors.lastname: Mora-Montes
keywords: Candida guilliermondii; cell wall; host-fungus interplay; mannosylation pathway; protein glycosylation; virulence