Screening of Chemical Libraries for New Antifungal Drugs against Aspergillus fumigatus Reveals Sphingolipids Are Involved in the Mechanism of Action of Miltefosine

Author:

dos Reis Thaila Fernanda12,Horta Maria Augusta Crivelente1,Colabardini Ana Cristina1,Fernandes Caroline Mota3,Silva Lilian Pereira1,Bastos Rafael Wesley1,Fonseca Maria Vitória de Lazari1,Wang Fang4,Martins Celso5,Rodrigues Márcio L.67,Silva Pereira Cristina5ORCID,Del Poeta Maurizio38910ORCID,Wong Koon Ho41112,Goldman Gustavo H.1ORCID

Affiliation:

1. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil

2. MicroControl Innovation Ltd., Ribeirão Preto, São Paulo, Brazil

3. Department of Microbiology and Immunology, Stony Brook University, Stony Brook, New York, USA

4. Faculty of Health Sciences, University of Macau, Taipa, Macau, SAR, China

5. Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa (ITQB NOVA), Oeiras, Portugal

6. Instituto Carlos Chagas (ICC), Fundação Oswaldo Cruz–Fiocruz, Curitiba, Brazil

7. Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

8. Veteran Administration Medical Center, Northport, New York, USA

9. MicroRid Technologies Inc., Dix Hills, New York, USA

10. Division of Infectious Diseases, School of Medicine, Stony Brook University, New York, USA

11. Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau, SAR, China

12. MoE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau, SAR, China

Abstract

The filamentous fungus Aspergillus fumigatus causes a group of diseases named aspergillosis, and their development occurs after the inhalation of conidia dispersed in the environment. Very few classes of antifungal drugs are available for aspergillosis treatment, e.g., azoles, but the emergence of global resistance to azoles in A. fumigatus clinical isolates has increased over recent decades.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

HHS | National Institutes of Health

UM | Research Services and Knowledge Transfer Office, University of Macau

U.S. Department of Veterans Affairs

MEC | Fundação para a Ciência e a Tecnologia

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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