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Proton pump inhibitors versus Cryptococcus species: effects on in vitro susceptibility and melanin production
Raimunda Sn Brilhante1, Maria G da Rocha2, Jonathas S de Oliveira1
1Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Department of Pathology & Legal Medicine, Federal University of Ceará. Rua Cel. Nunes de Melo, 1315 - Rodolfo Teófilo - CEP: 60430-275, Fortaleza, Ceará, Brazil.
Abstract:
Aim: This study aimed to evaluate the effects of proton pump inhibitors (PPIs) on growth and melanin production by Cryptococcus spp. Materials & methods: Minimum inhibitory concentrations (MICs) of omeprazole, esomeprazole, rabeprazole, pantoprazole and lansoprazole against Cryptococcus spp. were determined and the effect of PPIs on melanin production was evaluated, in the presence or absence of copper sulfate or glutathione. Results: PPIs showed MICs ranging from 125-1000 μg/ml and decreased melanization by Cryptococcus cells. Addition of copper sulfate or gluthatione restored melanogenesis of cells grown in the presence of PPIs. The presence of PPIs and glyphosate decreased copper sulfate toxicity (1 mM). Conclusion: PPIs inhibited melanogenesis of Cryptococcus spp., possibly by chelating copper or inhibiting copper ATPase transport.
Insights
Proton pump inhibitors (PPIs) were found to inhibit melanin production in Cryptococcus species. This effect may be due to PPIs chelating copper or affecting copper transport, impacting fungal growth.
Area of Science:
- Medical Mycology
- Pharmacology
- Infectious Diseases
Background:
- Cryptococcus species are opportunistic fungal pathogens.
- Melanin production is a key virulence factor for Cryptococcus.
- Proton pump inhibitors (PPIs) are widely used medications.
Purpose of the Study:
- To investigate the impact of various PPIs on Cryptococcus growth.
- To determine the effect of PPIs on melanin production by Cryptococcus.
- To elucidate the mechanism underlying PPIs' effect on melanization.
Main Methods:
- Determination of minimum inhibitory concentrations (MICs) for five PPIs against Cryptococcus.
- Evaluation of PPIs' effect on melanin production with and without copper sulfate or glutathione.
- Assessment of PPIs' influence on copper toxicity.
Main Results:
- PPIs demonstrated MICs between 125-1000 μg/ml.
- Melanization in Cryptococcus cells was reduced by PPIs.
- Copper sulfate or glutathione addition reversed the inhibition of melanogenesis.
- PPIs and glyphosate reduced copper toxicity.
Conclusions:
- PPIs inhibit melanogenesis in Cryptococcus species.
- The mechanism may involve copper chelation or inhibition of copper ATPase transport.
- Further research is needed to confirm these findings and their clinical implications.
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