HPLC-MS identification and expression of <i>Candida</i> 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; 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

AIMS Microbiology

2021, Volume 7, Issue 3: 320-335. doi: 10.3934/microbiol.2021020

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Research article

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

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

Received: 19 May 2021 Accepted: 23 August 2021 Published: 10 September 2021

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.
- Candida,
- drug resistance,
- HPLC-MS,
- protein expression,
- HIV
Citation: Pedro M D S Abrantes, Randall Fisher, Patrick J D Bouic, Carole P McArthur, Burtram C Fielding, Charlene W J Africa. HPLC-MS identification and expression of Candida drug-resistance proteins from African HIV-infected patients[J]. AIMS Microbiology, 2021, 7(3): 320-335. doi: 10.3934/microbiol.2021020

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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.

Acknowledgments

This material is based upon work partially supported financially by the National Research Foundation of South Africa [Grant number TTK2008052700013]. Any opinion, findings and conclusions or recommendations expressed in this material are those of the authors and therefore the NRF does not accept any liability in regards thereto.
Our sincere gratitude is expressed to the patients who willingly participated in this study. We also wish to acknowledge the passing of our wonderful colleague, collaborator and friend, Dr Leo Ayuk Njock of Bamenda, Cameroon due to Covid 19. Dr Ayuk worked assiduously for several months to recruit the Cameroonian cohort from which half of these patients were selected.

Conflict of interest

All authors declare no conflicts of interest in this paper.

Authors' contributions

CA conceptualized the study, participated in its design, coordination and writing of the manuscript. PA performed the laboratory isolation, identification, drug susceptibility and cell fractioning of the Candida isolates, analysed the data and prepared the first draft of the manuscript. RF assisted with the protocol for the isolation of the cell fractions and contributed to the writing of the manuscript. PB participated in the study's design and coordination and facilitated sample collection in South Africa. BF assisted with the protocol for the isolation of the cell fractions. CM facilitated the recruitment and specimen collection in Cameroon and contributed to the final revision of the manuscript.

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