Universidad Complutense de Madrid
E-Prints Complutense

Targeting Aspergillus fumigatus Crf Transglycosylases With Neutralizing Antibody Is Relevant but Not Sufficient to Erase Fungal Burden in a Neutropenic Rat Model

Impacto

Downloads

Downloads per month over past year

Chauvin, David and Hust, Michael and Schütte, Mark and Chesnay, Adélaïde and Parent, Christelle and Moreira, Gustavo Marçal Schmidt Garcia and Arroyo, Javier and Sanz Santamaría, Ana Belén and Pugnière, Martine and Martineau, Pierre and Chandenier, Jacques and Heuzé-Vourc'h, Nathalie and Desoubeaux, Guillaume and Parentani, R. (2019) Targeting Aspergillus fumigatus Crf Transglycosylases With Neutralizing Antibody Is Relevant but Not Sufficient to Erase Fungal Burden in a Neutropenic Rat Model. Frontiers in Microbiology, 10 . p. 600. ISSN 1664-302X

[img]
Preview
PDF
Creative Commons Attribution.

2MB

Official URL: https://www.frontiersin.org/



Abstract

is an airborne opportunistic fungal pathogen responsible for severe infections. Among them, invasive pulmonary aspergillosis has become a major concern as mortality rates exceed 50% in immunocompromised hosts. In parallel, allergic bronchopulmonary aspergillosis frequently encountered in cystic fibrosis patients, is also a comorbidity factor. Current treatments suffer from high toxicity which prevents their use in weakened subjects, resulting in impaired prognostic. Because of their low toxicity and high specificity, anti-infectious therapeutic antibodies could be a new alternative to conventional therapeutics. In this study, we investigated the potential of cell wall transglycosylases of to be therapeutic targets for therapeutic antibodies. We demonstrated that the Crf target was highly conserved, regardless of the pathophysiological context; whereas the gene was found to be 100% conserved in 92% of the isolates studied, Crf proteins were expressed in 98% of the strains. In addition, we highlighted the role of Crf proteins in fungal growth, using a deletion mutant for gene, for which a growth decrease of 23.6% was observed after 48 h. It was demonstrated that anti-Crf antibodies neutralized the enzymatic activity of recombinant Crf protein, and delayed fungal growth by 12.3% when added to spores. In a neutropenic rat model of invasive pulmonary aspergillosis, anti-Crf antibodies elicited a significant recruitment of neutrophils, macrophages and T CD4 lymphocytes but it was not correlated with a decrease of fungal burden in lungs and improvement in survival. Overall, our study highlighted the potential relevance of targeting Crf cell wall protein (CWP) with therapeutic antibodies.


Item Type:Article
Uncontrolled Keywords:Aspergillus, Fungi, Invasive pulmonary aspergillosis, Cell wall, Crf1, Crh5, Glycosyltransferase, Monoclonal antibody
Subjects:Medical sciences > Medicine > Communicable diseases
Medical sciences > Pharmacy > Cytology
Medical sciences > Pharmacy > Microbiology
Medical sciences > Pharmacy > Pharmaceutical technology
ID Code:55684
Deposited On:11 Jun 2019 08:04
Last Modified:11 Jun 2019 11:50

Origin of downloads

Repository Staff Only: item control page