Pseudomonas Synergizes with Fluconazole against Candida during Treatment of Polymicrobial Infection

Area of Science:

• Microbiology
• Infectious Diseases
• Antimicrobial Resistance

Background:

• Polymicrobial infections present treatment challenges due to complex pathogen interactions and variable drug efficacy.
• Candida albicans and Pseudomonas aeruginosa are opportunistic pathogens frequently co-infecting vulnerable patient populations.
• Limited antifungal agents and their fungistatic nature complicate Candida albicans treatment.

Purpose of the Study:

• To investigate the efficacy of antifungal treatment during Candida albicans-Pseudomonas aeruginosa co-culture and co-infection.
• To elucidate the mechanisms underlying drug synergy in polymicrobial infections.
• To evaluate antifungal drug effectiveness in a relevant host-pathogen model.

Main Methods:

• In vitro co-culture models of Candida albicans and Pseudomonas aeruginosa.
• Mucosal zebrafish infection model for polymicrobial co-infection studies.
• Iron supplementation and bacterial siderophore knockout experiments to assess mechanisms.

Main Results:

• Pseudomonas aeruginosa significantly enhanced the fungistatic antifungal fluconazole (FLC) to achieve fungal killing in vitro.
• FLC treatment promoted clearance of Candida albicans during co-infection in vivo.
• The observed synergy was partly attributed to bacterial iron piracy, as it was reduced by iron supplementation and siderophore deficiency.

Conclusions:

• Fluconazole exhibits enhanced antifungal activity in the context of polymicrobial infections.
• Bacterial interactions, such as iron piracy, can modulate antifungal drug efficacy.
• Understanding microbial communities is crucial for optimizing antimicrobial strategies in clinical settings.