title: Post-antifungal effects of the antifungal compound 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1-methylethyl pentanoate on Aspergillus fumigatus.
abstract: The post-antifungal effect (PAFE) of the antifungal compound 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1-methylethyl pentanoate (DHP) upon Aspergillus fumigatus was investigated. The conidia of A. fumigatus were exposed to DHP at concentrations of 1 x and 4 x MIC(90) for variable times at 37 degrees C. Amphotericin B (AmB)-treated or drug-free controls were included in the study. DHP as well as AmB exposure resulted in prolonged lag phases of the turbidimetric growth curves. Both the treatments gave rise to delayed growth, with lag phases of 11 h upon treatment with a concentration of 4 x MIC(90) for 4 h. Furthermore, it was observed that DHP inhibited the expression of three A. fumigatus secretory proteins of 18, 42 and 55 kDa. One protein of 42 kDa was found to be a metalloprotease, which is an important virulence factor. Analysis of time-dependent antigenic profiles showed the early expression of high-molecular-mass antigens. Expression of low-molecular-mass antigens started after 24 h culture. The antigens of A. fumigatus that are expressed during the early phase of growth were observed to be adversely affected after treatment with DHP. Although the mechanism of action of DHP to inhibit these proteins/antigens is unknown, the observations may be valuable to understand their role in the virulence of the pathogen, as well as the antigen-mediated responses caused by A. fumigatus.
authors.affiliation: Regional Research Institute (Ay), Nehru Garden, Kothrud, Pune 411 038, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Dabur
authors.affiliation: Regional Research Institute (Ay), Nehru Garden, Kothrud, Pune 411 038, India.
authors.forename: T K
authors.initials: TK
authors.lastname: Mandal
authors.affiliation: Institute of Genomics and Integrative Biology, Mall Road, Delhi 110 007, India.
authors.forename: G L
authors.initials: GL
authors.lastname: Sharma
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D000946:Antigens, Fungal / Q000096:biosynthesis / Q000737:chemistry; D001228:Aspergillosis / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000254:growth & development; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006801:Humans; D045726:Metalloproteases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008970:Molecular Weight; D011758:Pyrroles / Q000494:pharmacology*; D014631:Valerates / Q000494:pharmacology*; D037521:Virulence Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: C488953:2beta-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1'-methylethyl pentanoate; D000935:Antifungal Agents; D000946:Antigens, Fungal; D005656:Fungal Proteins; D011758:Pyrroles; D014631:Valerates; D037521:Virulence Factors; D000666:Amphotericin B; D045726:Metalloproteases