HPLC-MS identification and expression of Candida drug-resistance proteins from African HIV-infected patients

Pedro M D S Abrantes; Randall Fisher; Patrick J D Bouic; Carole P McArthur; Burtram C Fielding; Charlene W J Africa

doi:10.3934/microbiol.2021020

HPLC-MS identification and expression of Candida drug-resistance proteins from African HIV-infected patients

AIMS Microbiol. 2021 Sep 10;7(3):320-335. doi: 10.3934/microbiol.2021020. eCollection 2021.

Authors

Pedro M D S Abrantes¹, Randall Fisher², Patrick J D Bouic³, Carole P McArthur⁴, Burtram C Fielding⁵, Charlene W J Africa¹

Affiliations

¹ Maternal Endogenous Infections Studies (MEnIS) Research Laboratories, Department of Medical Biosciences, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa.
² Separated Sector Cyclotron Laboratory, iThemba LABS, Radiation Biophysics Division, National Research Foundation, Cape Town, South Africa.
³ Synexa Life Sciences, PO Box 36596, Chempet 7442, South Africa.
⁴ Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, MO 64108, USA.
⁵ Molecular Biology and Virology Laboratory, Department of Medical Biosciences, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa.

Abstract

The objective of this study was to elucidate the proteomic mechanisms of drug resistance in HIV-infected African patients. Cell membrane fractions from forty oral Candida isolates isolated from African HIV-positive patients were analysed using HPLC-MS with the aim of identifying proteins associated with their pathogenicity and drug resistance. Heat shock proteins that mediate the fungicidal activity of salivary peptides were found in all tested Candida fractions, with pH-responsive proteins associated with increased pathogenicity only being present in the three most commonly isolated species. ABC multidrug transporter efflux pumps and estrogen binding proteins were only found in C. albicans fractions, while ergosterol biosynthesis proteins were identified in four species. The combination of various adherence, invasion, upregulation and efflux pump mechanisms appear to be instrumental for the Candida host colonization and drug resistance emergence in HIV-infected individuals.

Keywords: Candida; HIV; HPLC-MS; drug resistance; protein expression.