Administration of Zinc Chelators Improves Survival of Mice Infected with Aspergillus fumigatus both in Monotherapy and in Combination with Caspofungin.

Paris Laskaris; Ahmad Atrouni; José Antonio Calera; Christophe d'Enfert; Hélène Munier-Lehmann; Jean-Marc Cavaillon; Jean-Paul Latgé; Oumaïma Ibrahim-Granet

Administration of Zinc Chelators Improves Survival of Mice Infected with Aspergillus fumigatus both in Monotherapy and in Combination with Caspofungin.

Paris Laskaris ¹ Ahmad Atrouni ¹ José Antonio Calera ² Christophe d'Enfert ³ Hélène Munier-Lehmann ⁴ Jean-Marc Cavaillon ¹ Jean-Paul Latgé ⁵ Oumaïma Ibrahim-Granet ^{1, *}

* Corresponding author

1 Cytokines et Inflammation

2 Universidad de Salamanca

3 Biologie et Pathogénicité fongiques

4 Chimie et Biocatalyse

5 Aspergillus

Abstract : Aspergillus fumigatus can infect immunocompromised patients, leading to high mortality rates due to the lack of reliable treatment options. This pathogen requires uptake of zinc from host tissues in order to successfully grow and cause virulence. Reducing the availability of that micronutrient could help treat A. fumigatus infections. In this study, we examined the in vitro effects of seven chelators using a bioluminescent strain of A. fumigatus 1,10-Phenanthroline and N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine (TPEN) proved to be the chelators most effective at inhibiting fungal growth. Intraperitoneal administration of either phenanthroline or TPEN resulted in a significant improvement in survival and decrease of weight loss and fungal burden for immunosuppressed mice intranasally infected with A. fumigatus In vitro both chelators had an indifferent effect when employed in combination with caspofungin. The use of TPEN in combination with caspofungin also significantly increased survival compared to that when using these drugs individually. Our results suggest that zinc chelation may be a valid strategy for dealing with A. fumigatus infections and that both phenanthroline and TPEN could potentially be used either independently or in combination with caspofungin, indicating that their use in combination with other antifungal treatments might also be applicable.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Microbiology and Parasitology / Mycology

Complete list of metadatas

https://hal-pasteur.archives-ouvertes.fr/pasteur-01515325
Contributor : Christelle Lenormand <>
Submitted on : Thursday, April 27, 2017 - 12:15:23 PM
Last modification on : Tuesday, February 13, 2018 - 3:48:04 PM

Administration of Zinc Chelators Improves Survival of Mice Infected with Aspergillus fumigatus both in Monotherapy and in Combination with Caspofungin.

Links full text

Identifiers

Collections

Citation

Export

Metrics

142

Contact

Administration of Zinc Chelators Improves Survival of Mice Infected with Aspergillus fumigatus both in Monotherapy and in Combination with Caspofungin.

Links full text

Identifiers

Collections

Citation

Export

Share

Metrics

142

Contact