Abstract:
:Scedosporium apiospermum is an emerging agent of opportunistic mycoses in humans. Previously, we showed that mycelia of S. apiospermum secreted metallopeptidases which were directly linked to the destruction of key host proteins. In this study, we analysed the effect of metallopeptidase inhibitors on S. apiospermum development. As germination of inhaled conidia is a crucial event in the infectious process of S. apiospermum, we studied the morphological transformation induced by the incubation of conidia in Sabouraud-dextrose medium at 37 °C. After 6 h, some conidia presented a small projection resembling a germ-tube. A significant increase, around sixfold, in the germ-tube length was found after 12 h, and hyphae were exclusively observed after 24 h. Three distinct metallopeptidase inhibitors were able to arrest the transformation of conidia into hyphae in different ways; for instance, 1,10-phenanthroline (PHEN) completely blocked this process at 10 μmol l(-1), while ethylenediamine tetraacetic acid (EDTA) and ethylene glycol-bis (β-aminoethyl ether; EGTA) only partially inhibited the differentiation at up to 10 mmol l(-1). EGTA did not promote any significant reduction in the conidial growth, while PHEN and EDTA, both at 10 mmol l(-1), inhibited the proliferation around 100% and 65%, respectively. The secretion of polypeptides into the extracellular environment and the metallopeptidase activity secreted by mycelia were completely inhibited by PHEN. These findings suggest that metallo-type enzymes could be potential targets for future therapeutic interventions against S. apiospermum.
journal_name
Mycosesjournal_title
Mycosesauthors
Silva BA,Souza-Gonçalves AL,Pinto MR,Barreto-Bergter E,Santos ALdoi
10.1111/j.1439-0507.2009.01767.xsubject
Has Abstractpub_date
2011-03-01 00:00:00pages
105-12issue
2eissn
0933-7407issn
1439-0507pii
MYC1767journal_volume
54pub_type
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