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.

Future Microbiology
|April 30, 2019
PubMed

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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