Palmitoylethanolamide shows limited efficacy in controlling cerebral cryptococcosis in vivo

( ) is an encapsulated neurotropic fungal pathogen and the causative agent of cryptococcal meningoencephalitis (CME) in humans. Recommended treatment for CME is Amphotericin B (AmpB) and 5-fluorocytosine (5-FC). Though effective, AmpB has displayed numerous adverse side effects due to its potency an...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2023-10, Vol.67 (10), p.e0045923-e0045923
Main Authors: Munzen, Melissa E, Reguera Gomez, Marta, Hamed, Mohamed F, Enriquez, Vanessa, Charles-Niño, Claudia L, Dores, Michael R, Alviña, Karina, Martinez, Luis R
Format: Article
Language:English
Subjects:
Amphotericin B - therapeutic use
Animals
Antifungal Agents - therapeutic use
Cryptococcosis - drug therapy
Cryptococcosis - microbiology
Cryptococcus neoformans
Experimental Therapeutics
Flucytosine - therapeutic use
Humans
Meningitis, Cryptococcal - drug therapy
Meningitis, Cryptococcal - microbiology
Meningoencephalitis - drug therapy
Mice
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Summary:( ) is an encapsulated neurotropic fungal pathogen and the causative agent of cryptococcal meningoencephalitis (CME) in humans. Recommended treatment for CME is Amphotericin B (AmpB) and 5-fluorocytosine (5-FC). Though effective, AmpB has displayed numerous adverse side effects due to its potency and nephrotoxicity, prompting investigation into alternative treatments. Palmitoylethanolamide (PEA) is an immunomodulatory compound capable of promoting neuroprotection and reducing inflammation. To investigate the efficacy of PEA as a therapeutic alternative for CME, we intracerebrally infected mice with and treated them with PEA or AmpB alone or in combination. Our results demonstrate that PEA alone does not significantly prolong survival nor reduce fungal burden, but when combined with AmpB, PEA exerts an additive effect and promotes both survivability and fungal clearance. However, we compared this combination to traditional AmpB and 5-FC treatment in a survivability study and observed lower efficacy. Overall, our study revealed that PEA alone is not effective as an antifungal agent in the treatment of CME. Importantly, we describe the therapeutic capability of PEA in the context of infection and show that its immunomodulatory properties may confer limited protection when combined with an effective fungicidal agent.
ISSN:0066-4804
1098-6596
DOI:10.1128/aac.00459-23