Differential expression of Aspergillus fumigatus protein in response to treatment with a novel antifungal compound, diethyl 4-(4-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarboxylate.
A dihydropyridine derivative, diethyl 4-(4-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarboxylate (2e), having potent antifungal activity against pathogenic species of Aspergillus was investigated for its possible molecular mechanism of action. The SDS-PAGE coupled with nano-high-performance liquid chromatography-tandem mass spectrometry was used directly to assess both absolute abundance and differential expression of proteins in the secretory phases of Aspergillus fumigatus under the influence of 2e. It was observed that the compound inhibited the expression of two proteins of 60.99 and 79.77 kDa. Both of these secretory proteins that were inhibited by 2e, were analysed further by matrix assisted laser desorption ionization time-of-flight mass spectrometry. The 60.99- and 79.77-kDa proteins were identified as probable retroelement pol polyprotein and elongation factor G respectively. These targeted proteins could be the products of potentially virulence-related genes of A. fumigatus which may unravel the mode of action of 2e and pathobiology of A. fumigatus.
Chhillar
A K
AK
Shriram Institute for Industrial Research, Delhi, India.
Yadav
V
V
Kumar
A
A
Kumar
M
M
Parmar
V S
VS
Prasad
A
A
Sharma
G L
GL
D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D008969:Molecular Sequence Data; D008970:Molecular Weight
D000935:Antifungal Agents; D004095:Dihydropyridines; D005656:Fungal Proteins; C541366:diethyl 4-(4-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarboxylate