title: Identification of novel secreted proteases during extracellular proteolysis by dermatophytes at acidic pH.
abstract: The dermatophytes are a group of closely related fungi which are responsible for the great majority of superficial mycoses in humans and animals. Among various potential virulence factors, their secreted proteolytic activity attracts a lot of attention. Most dermatophyte-secreted proteases which have so far been isolated in vitro are neutral or alkaline enzymes. However, inspection of the recently decoded dermatophyte genomes revealed many other hypothetical secreted proteases, in particular acidic proteases similar to those characterized in Aspergillus spp. The validation of such genome predictions instigated the present study on two dermatophyte species, Microsporum canis and Arthroderma benhamiae. Both fungi were found to grow well in a protein medium at acidic pH, accompanied by extracellular proteolysis. Shotgun MS analysis of secreted protein revealed fundamentally different protease profiles during fungal growth in acidic versus neutral pH conditions. Most notably, novel dermatophyte-secreted proteases were identified at acidic pH such as pepsins, sedolisins and acidic carboxypeptidases. Therefore, our results not only support genome predictions, but demonstrate for the first time the secretion of acidic proteases by dermatophytes. Our findings also suggest the existence of different pathways of protein degradation into amino acids and short peptides in these highly specialized pathogenic fungi.
authors.affiliation: Department of Dermatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Dev
authors.initials: D
authors.lastname: Sriranganadane
authors.forename: Patrice
authors.initials: P
authors.lastname: Waridel
authors.forename: Karine
authors.initials: K
authors.lastname: Salamin
authors.forename: Marc
authors.initials: M
authors.lastname: Feuermann
authors.forename: Bernard
authors.initials: B
authors.lastname: Mignon
authors.forename: Peter
authors.initials: P
authors.lastname: Staib
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Neuhaus
authors.forename: Manfredo
authors.initials: M
authors.lastname: Quadroni
authors.forename: Michel
authors.initials: M
authors.lastname: Monod
mesh_terms: D003883:Arthrodermataceae / Q000201:enzymology* / Q000502:physiology; D003470:Culture Media / Q000737:chemistry / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005110:Extracellular Space; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D008864:Microsporum / Q000201:enzymology* / Q000502:physiology; D010436:Pepstatins; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism; D010449:Peptide Mapping; D059748:Proteolysis; D030262:Soybean Proteins
chemical_list: D003470:Culture Media; D010436:Pepstatins; D030262:Soybean Proteins; D010447:Peptide Hydrolases; C031375:pepstatin