Microbial function and genital inflammation in young South African women at high risk of HIV infection
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RESEARCH
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Microbial function and genital inflammation in young South African women at high risk of HIV infection Arghavan Alisoltani1,2, Monalisa T. Manhanzva1, Matthys Potgieter3,4, Christina Balle5, Liam Bell6, Elizabeth Ross6, Arash Iranzadeh3, Michelle du Plessis6, Nina Radzey1, Zac McDonald6, Bridget Calder4, Imane Allali3,7, Nicola Mulder3,8,9, Smritee Dabee1,10, Shaun Barnabas1, Hoyam Gamieldien1, Adam Godzik2, Jonathan M. Blackburn4,8, David L. Tabb8,11,12, Linda-Gail Bekker8,13, Heather B. Jaspan5,8,10, Jo-Ann S. Passmore1,8,14,15 and Lindi Masson1,8,14,16,17*
Abstract Background: Female genital tract (FGT) inflammation is an important risk factor for HIV acquisition. The FGT microbiome is closely associated with inflammatory profile; however, the relative importance of microbial activities has not been established. Since proteins are key elements representing actual microbial functions, this study utilized metaproteomics to evaluate the relationship between FGT microbial function and inflammation in 113 young and adolescent South African women at high risk of HIV infection. Women were grouped as having low, medium, or high FGT inflammation by K-means clustering according to pro-inflammatory cytokine concentrations. Results: A total of 3186 microbial and human proteins were identified in lateral vaginal wall swabs using liquid chromatography-tandem mass spectrometry, while 94 microbial taxa were included in the taxonomic analysis. Both metaproteomics and 16S rRNA gene sequencing analyses showed increased non-optimal bacteria and decreased lactobacilli in women with FGT inflammatory profiles. However, differences in the predicted relative abundance of most bacteria were observed between 16S rRNA gene sequencing and metaproteomics analyses. Bacterial protein functional annotations (gene ontology) predicted inflammatory cytokine profiles more accurately than bacterial relative abundance determined by 16S rRNA gene sequence analysis, as well as functional predictions based on 16S rRNA gene sequence data (p < 0.0001). The majority of microbial biological processes were underrepresented in women with high inflammation compared to those with low inflammation, including a Lactobacillus-associated signature of reduced cell wall organization and peptidoglycan biosynthesis. This signature remained associated with high FGT inflammation in a subset of 74 women 9 weeks later, was upheld after adjusting for Lactobacillus relative abundance, and was associated with in vitro inflammatory cytokine responses to Lactobacillus isolates from the same women. Reduced cell wall organization and peptidoglycan biosynthesis were also associated with high FGT (Continued on next page)
* Correspondence: [email protected] 1 Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa 8 Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town 7925, South Africa Full list of author information is available at the end of the artic
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