ASP2397, a novel natural compound that exhibits rapid and potent fungicidal activity against Aspergillus species through a specific transporter.

ASP2397, a novel natural compound that exhibits rapid and potent fungicidal activity against Aspergillus species through a specific transporter. Antimicrob Agents Chemother. 2019 Aug 12;: Authors: Nakamura I, Ohsumi K, Takeda S, Katsumata K, Matsumoto S, Akamatsu S, Mitori H, Nakai T Abstract Current therapies against invasive pulmonary aspergillosis (IPA) have a limited cure rate. Given that a delay in treatment initiation may be fatal, a new drug with rapid -onset and potent antifungicidal activity is needed. The novel cyclic hexapeptide ASP2397 (currently known as VL-2397) exhibited antifungal activity against Aspergillus fumigatus (including azole-sensitive and azole-resistant isolates), A. terreus, and A. flavus at a MIC range of 1 to 4 μg/ml in human serum. Time-kill curve experiments showed that ASP2397 reduced germinated conidia of A. fumigatu by more than 1-log10 CFUs within 6 hours. In addition, ASP2397 inhibited hyphal elongation from germinated conidia of A. fumigatus, A. terreus, and A. flavus more rapidly than voriconazole. When treatment initiation was delayed in an IPA mouse model, ASP2397 had superior efficacy over posaconazole, with 100% survival and over 1-log10 CFU/g reduction in lung fungal burden. Histopathological investigation of lungs also showed that ASP2397 markedly suppressed disease progression. To clarify its mechanism of action, we generated a UV-induced mutant of A. fumigatus with low susceptibility t...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research