Increase of reactive oxygen species contributes to growth inhibition by fluconazole in Cryptococcus neoformans

Authors

Nadir Hani Dbouk, Furman UniversityFollow
Madison Bailey Covington, Furman UniversityFollow
Kenny Nguyen, Furman UniversityFollow
Srikripa Chandrasekaran, Furman UniversityFollow

Document Type

Article (Journal or Newsletter)

Scholarship Type

Faculty Scholarship, Student Scholarship

Publication Date

11-6-2019

Abstract

Background

Cryptococcus neoformans, a basidiomycetous yeast, is a fungal pathogen that can colonize the lungs of humans causing pneumonia and fungal meningitis in severely immunocompromised individuals. Recent studies have implied that the antifungal drug fluconazole (FLC) can induce oxidative stress in C. neoformans by increasing the production of reactive oxygen species (ROS), as presence of the antioxidant ascorbic acid (AA) could reverse the inhibitory effects of FLC on C. neoformans. However, in Candida albicans, AA has been shown to stimulate the expression of genes essential for ergosterol biosynthesis. Hence, the contribution of ROS in FLC-mediated growth inhibition remains unclear.

Results

In order to determine whether counteracting ROS generated by FLC in C. neoformans can contribute to diminishing inhibitory effects of FLC, we tested three other antioxidants in addition to AA, namely, pyrrolidine dithiocarbamate (PDTC), retinoic acid (RA), and glutathione (GSH). Our data confirm that there is an increase in ROS in the presence of FLC in C. neoformans. Importantly, all four antioxidants reversed FLC-mediated growth inhibition of C. neoformans to various extents. We further verified the involvement of increased ROS in FLC-mediated growth inhibition by determining that ROS-scavenging proteins, metallothioneins (CMT1 and CMT2), contribute to growth recovery by PDTC and AA during treatment with FLC.

Conclusion

Our study suggests that ROS contributes to FLC-mediated growth inhibition and points to a complex nature of antioxidant-mediated growth rescue in the presence of FLC.

Comments

Open access publication of this article was supported by the Furman University Libraries Open Access Fund.

Additional Affiliated Department, Center or Institute

Biology

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Recommended Citation

Dbouk, N.H., Covington, M.B., Nguyen, K. et al. Increase of reactive oxygen species contributes to growth inhibition by fluconazole in Cryptococcus neoformans. BMC Microbiol 19, 243 (2019). https://doi.org/10.1186/s12866-019-1606-4