A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome

Nyaradzo T L Chigorimbo-Murefu; Matthys Potgieter; Sonwabile Dzanibe; Zikhona Gabazana; Gershom Buri; Aditya Chawla; Bokani Nleya; Abraham J Olivier; Rushil Harryparsad; Bridget Calder; Shaun Garnett; Lungile Maziya; David A Lewis; Heather Jaspan; Doug Wilson; Jo-Ann S Passmore; Nicola Mulder; Jonathan Blackburn; Linda-Gail Bekker; Clive M Gray

doi:10.3389/fmicb.2022.928317

A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome

Front Microbiol. 2022 Oct 17:13:928317. doi: 10.3389/fmicb.2022.928317. eCollection 2022.

Authors

Nyaradzo T L Chigorimbo-Murefu¹, Matthys Potgieter^{2

3}, Sonwabile Dzanibe⁴, Zikhona Gabazana², Gershom Buri⁴, Aditya Chawla⁴, Bokani Nleya⁴, Abraham J Olivier⁴, Rushil Harryparsad¹, Bridget Calder³, Shaun Garnett³, Lungile Maziya⁵, David A Lewis^{6

7}, Heather Jaspan^{4

8

9}, Doug Wilson⁵, Jo-Ann S Passmore¹, Nicola Mulder², Jonathan Blackburn³, Linda-Gail Bekker¹⁰, Clive M Gray^{4

11}

Affiliations

¹ Divisions of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
² Division of Computational Biology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
³ Division of Chemical and Systems Biology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
⁴ Division of Immunology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
⁵ Department of Medicine, Edendale Hospital, Pietermaritzburg, South Africa.
⁶ Western Sydney Sexual Health Centre, Western Sydney Local Health District, Parramatta, NSW, Australia.
⁷ Westmead Clinical School and Sydney Institute for Infectious Diseases, University of Sydney, Sydney, NSW, Australia.
⁸ Seattle Children's Research Institute, Seattle, WA, United States.
⁹ Department of Global Health, University of Washington, Seattle, WA, United States.
¹⁰ Desmond Tutu HIV Centre, Cape Town, South Africa.
¹¹ Division of Molecular Biology and Human Genetics, Stellenbosch University, Cape Town, South Africa.

Abstract

There is limited data on the role of asymptomatic STIs (aSTIs) on the risk of human immunodeficiency virus (HIV) acquisition in the male genital tract (MGT). The impact of foreskin removal on lowering HIV acquisition is well described, but molecular events leading to HIV acquisition are unclear. Here, in this pilot study, we show that asymptomatic urethral infection with Chlamydia trachomatis (CT) significantly impacts the foreskin proteome composition. We developed and optimized a shotgun liquid chromatography coupled tandem mass spectrometry (MS)-based proteomics approach and utilized this on foreskins collected at medical male circumcision (MMC) from 16 aSTI⁺ men and 10 age-matched STI- controls. We used a novel bioinformatic metaproteomic pipeline to detect differentially expressed (DE) proteins. Gene enrichment ontology analysis revealed proteins associated with inflammatory and immune activation function in both inner and outer foreskin from men with an aSTI. Neutrophil activation/degranulation and viral-evasion proteins were significantly enriched in foreskins from men with aSTI, whereas homotypic cell-cell adhesion proteins were enriched in foreskin tissue from men without an aSTI. Collectively, our data show that asymptomatic urethral sexually transmitted infections result in profound alterations in epithelial tissue that are associated with depletion of barrier integrity and immune activation.

Keywords: HIV susceptibility; asymptomatic sexually transmitted infection; foreskin; foreskin proteome; gene ontology enrichment analysis.

Copyright © 2022 Chigorimbo-Murefu, Potgieter, Dzanibe, Gabazana, Buri, Chawla, Nleya, Olivier, Harryparsad, Calder, Garnett, Maziya, Lewis, Jaspan, Wilson, Passmore, Mulder, Blackburn, Bekker and Gray.

Grants and funding

R01 DK108434/DK/NIDDK NIH HHS/United States