Preclinical Evaluation of Recombinant Microbial Glycoside Hydrolases in the Prevention of Experimental Invasive Aspergillosis.
Animals
Antifungal Agents
/ administration & dosage
Aspergillus fumigatus
/ pathogenicity
Biofilms
/ drug effects
Disease Models, Animal
Drug Evaluation, Preclinical
Female
Glycoside Hydrolases
/ administration & dosage
Invasive Pulmonary Aspergillosis
/ microbiology
Mice
Mice, Inbred BALB C
Neutropenia
Recombinant Proteins
/ administration & dosage
Virulence
Aspergillus fumigatus
antifungal agents
antimicrobial combinations
biofilm
exopolysaccharide
filamentous fungi
galactosaminogalactan (GAG)
glycoside hydrolase (GH)
pulmonary aspergillosis
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
26 10 2021
26 10 2021
Historique:
pubmed:
29
9
2021
medline:
28
1
2022
entrez:
28
9
2021
Statut:
ppublish
Résumé
Aspergillus fumigatus is a ubiquitous mold that can cause invasive pulmonary infections in immunocompromised patients. Within the lung, A. fumigatus forms biofilms that can enhance resistance to antifungals and immune defenses. Aspergillus biofilm formation requires the production of a cationic matrix exopolysaccharide, galactosaminogalactan (GAG). In this study, recombinant glycoside hydrolases (GH)s that degrade GAG were evaluated as antifungal agents in a mouse model of invasive aspergillosis. Intratracheal GH administration was well tolerated by mice. Pharmacokinetic analysis revealed that although GHs have short half-lives, GH prophylaxis resulted in reduced fungal burden in leukopenic mice and improved survival in neutropenic mice, possibly through augmenting pulmonary neutrophil recruitment. Combining GH prophylaxis with posaconazole treatment resulted in a greater reduction in fungal burden than either agent alone. This study lays the foundation for further exploration of GH therapy in invasive fungal infections.
Identifiants
pubmed: 34579578
doi: 10.1128/mBio.02446-21
pmc: PMC8546845
doi:
Substances chimiques
Antifungal Agents
0
Recombinant Proteins
0
Glycoside Hydrolases
EC 3.2.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
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