title: Lysozyme plays a dual role against the dimorphic fungus Paracoccidioides brasiliensis.
abstract: In order to determine the role of lysozyme, an antimicrobial peptide belonging to the innate immune system, against the dimorphic fungus Paracoccidioides brasiliensis, co-cultures of the MH-S murine alveolar macrophages cell line with P. brasiliensis conidia were done; assays to evaluate the effect of physiological and inflammatory concentrations of lysozyme directly on the fungus life cycle were also undertaken. We observed that TNF-alpha-activated macrophages significantly inhibited the conidia to yeast transition (p = 0.0043) and exerted an important fungicidal effect (p = 0.0044), killing 27% more fungal propagules in comparison with controls. Nonetheless, after adding a selective inhibitor of lysozyme, the fungicidal effect was reverted. When P. brasiliensis propagules were exposed directly to different concentrations of lysozyme, a dual effect was observed. Physiologic concentrations of the enzyme facilitated the conidia-to-yeast transition process (p < 0.05). On the contrary, inflammatory concentrations impaired the normal temperature-dependent fungal transition (p < 0.0001). When yeast cells were exposed to lysozyme, irrespective of concentration, the multiple-budding ability was badly impaired (p < 0.0001). In addition, ultra-structural changes such as subcellular degradation, fusion of lipid vacuoles, lamellar structures and interruption of the fibrillar layer were observed in lysozyme exposed conidia. These results suggest that lysozyme appears to exert a dual role as part of the anti-P. brasiliensis defense mechanisms.
authors.affiliation: Medical and Experimental Mycology Group, Corporación para Investigaciones Biológicas, Carrera 72A No. 78B-141, Medellín, Colombia.
authors.forename: Damaris
authors.initials: D
authors.lastname: Lopera
authors.forename: Beatriz H
authors.initials: BH
authors.lastname: Aristizabal
authors.forename: Angela
authors.initials: A
authors.lastname: Restrepo
authors.forename: Luz Elena
authors.initials: LE
authors.lastname: Cano
authors.forename: Angel
authors.initials: A
authors.lastname: González
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D018920:Coculture Techniques / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008018:Life Cycle Stages / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009113:Muramidase / Q000494:pharmacology*; D010228:Paracoccidioides / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D016898:Interferon-alpha; D009113:Muramidase