AUTHOR=Chigorimbo-Murefu Nyaradzo T. L. , Potgieter Matthys , Dzanibe Sonwabile , Gabazana Zikhona , Buri Gershom , Chawla Aditya , Nleya Bokani , Olivier Abraham J. , Harryparsad Rushil , Calder Bridget , Garnett Shaun , Maziya Lungile , Lewis David A. , Jaspan Heather , Wilson Doug , Passmore Jo-Ann S. , Mulder Nicola , Blackburn Jonathan , Bekker Linda-Gail , Gray Clive M. TITLE=A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome JOURNAL=Frontiers in Microbiology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.928317 DOI=10.3389/fmicb.2022.928317 ISSN=1664-302X 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.