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Front Microbiol. 2016 Mar 08;7:306. doi: 10.3389/fmicb.2016.00306. eCollection 2016.

Role of Protein Glycosylation in Candida parapsilosis Cell Wall Integrity and Host Interaction.

Frontiers in microbiology

Luis A Pérez-García, Katalin Csonka, Arturo Flores-Carreón, Eine Estrada-Mata, Erika Mellado-Mojica, Tibor Németh, Luz A López-Ramírez, Renata Toth, Mercedes G López, Csaba Vizler, Annamaria Marton, Adél Tóth, Joshua D Nosanchuk, Attila Gácser, Héctor M Mora-Montes

Affiliations

  1. Departamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato Guanajuato, Mexico.
  2. Department of Microbiology, University of Szeged Szeged, Hungary.
  3. Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional Irapuato, Mexico.
  4. Biological Research Centre, Hungarian Academy of Sciences Szeged, Hungary.
  5. Department of Medicine and Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, NY, USA.

PMID: 27014229 PMCID: PMC4781877 DOI: 10.3389/fmicb.2016.00306

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.

Keywords: Candida parapsilosis; cell wall; host-fungus interplay; mannosylation pathway; mannosyltransferase; virulence

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