Hitting the caspofungin salvage pathway of human-pathogenic fungi with the novel lasso peptide humidimycin (MDN-0010)

Abstract:

Fungal infections have increased dramatically in the last 2 decades, and fighting infectious diseases requires innovative approaches such as the combination of two drugs acting on different targets or even targeting a salvage pathway of one of the drugs. The fungal cell wall biosynthesis is inhibited by the clinically used antifungal drug caspofungin. This antifungal activity has been found to be potentiated by humidimycin, a new natural product identified from the screening of a collection of 20,000 microbial extracts, which has no major effect when used alone. An analysis of transcriptomes and selected Aspergillus fumigatus mutants indicated that humidimycin affects the high osmolarity glycerol response pathway. By combining humidimycin and caspofungin, a strong increase in caspofungin efficacy was achieved, demonstrating that targeting different signaling pathways provides an excellent basis to develop novel anti-infective strategies.

SEEK ID: https://funginet.hki-jena.de/publications/70

PubMed ID: 26055366

Projects: B3 (E), FungiNet A - Aspergillus projects

Publication type: Not specified

Journal: Antimicrob Agents Chemother

Citation:

Date Published: 8th Jun 2015

Registered Mode: Not specified

Authors: , M. C. Monteiro, J. Martin, R. Altwasser, N. El Aouad, I. Gonzalez, , E. Mellado, S. Palomo, N. de Pedro, I. Perez-Victoria, J. R. Tormo, F. Vicente, F. Reyes, O. Genilloud,

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Created: 12th May 2016 at 08:54

Last updated: 17th Jan 2024 at 10:24

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