PUBLICATION
Pseudomonas Synergizes with Fluconazole against Candida during Treatment of Polymicrobial Infection
- Authors
- Hattab, S., Dagher, A.M., Wheeler, R.T.
- ID
- ZDB-PUB-220316-9
- Date
- 2022
- Source
- Infection and Immunity 90(4): e0062621 (Journal)
- Registered Authors
- Wheeler, Robert
- Keywords
- Candida, Pseudomonas aeruginosa, fluconazole, mucosal, polymicrobial, zebrafish
- MeSH Terms
-
- Animals
- Antifungal Agents/pharmacology
- Antifungal Agents/therapeutic use
- Candida
- Candida albicans
- Coinfection*/drug therapy
- Drug Resistance, Fungal
- Fluconazole*/pharmacology
- Fluconazole*/therapeutic use
- Humans
- Iron
- Microbial Sensitivity Tests
- Pseudomonas
- Pseudomonas aeruginosa
- Zebrafish
- PubMed
- 35289633 Full text @ Infect. Immun.
Citation
Hattab, S., Dagher, A.M., Wheeler, R.T. (2022) Pseudomonas Synergizes with Fluconazole against Candida during Treatment of Polymicrobial Infection. Infection and Immunity. 90(4):e0062621.
Abstract
Polymicrobial infections are challenging to treat because we don't fully understand how pathogens interact during infection and how these interactions affect drug efficacy. Candida albicans and Pseudomonas aeruginosa are opportunistic pathogens that can be found in similar sites of infection such as in burn wounds and most importantly in the lungs of CF and mechanically ventilated patients. C. albicans is particularly difficult to treat because of the paucity of antifungal agents, some of which lack fungicidal activity. In this study, we investigated the efficacy of anti-fungal treatment during C. albicans-P. aeruginosa coculture in vitro and co-infection in the mucosal zebrafish infection model analogous to the lung. We find that P. aeruginosa enhances the activity of fluconazole (FLC), an anti-fungal drug that is fungistatic in vitro, to promote both clearance of C. albicans during co-infection in vivo and fungal killing in vitro. This synergy between FLC treatment and bacterial antagonism is partly due to iron piracy, as it is reduced upon iron supplementation and knockout of bacterial siderophores. Our work demonstrates that FLC has enhanced activity in clinically relevant contexts and highlights the need to understand antimicrobial effectiveness in the complex environment of the host with its associated microbial communities.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping