Science Bite (3 minute oral presentation with PPT in live session and poster) - Students and ECRs only Lorne Infection and Immunity 2023

Functional differences between cervicovaginal Lactobacillus species that protect against HIV infection (#25)

Jenna Wilson 1 , Arghavan Alisoltani 2 3 , Monalisa T Manhanzva 2 3 , Grace Androga 1 , Matthys Potgieter 2 4 5 , Liam Bell 6 , Elizabeth Ross 6 , Arash Iranzadeh 2 4 , Imane Allali 4 7 8 , Nicola Mulder 2 4 9 , Smritee Dabee 2 3 10 , Shaun L Barnabas 3 11 , Hoyam Gamieldien 2 3 , Jonathan M Blackburn 2 5 , Linda-Gail Bekker 2 12 , Heather B Jaspan 2 10 13 , Jo-Ann S Passmore 2 3 14 15 , Lindi Masson 1 2 3 14 16
  1. Disease Elimination Program, Life Sciences Discipline, Burnet Institute, Melbourne, Victoria, Australia
  2. Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
  3. Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town, South Africa
  4. Computational Biology Division, Department of Integrative Biomedical Science, University of Cape Town, Cape Town, South Africa
  5. Division of Chemical and Systems Biology, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa
  6. Centre for Proteomic and Genomic Research, Cape Town, South Africa
  7. Faculty of Sciences, , University Mohammed V, Rabat, Morocco
  8. Laboratory of Human Pathologies Biology, Department of Biology and Genomic Center of Human Pathologies, Mohammed V University, Rabat, Morocco
  9. Centre for Infectious Diseases Research (CIDRI) in Africa Wellcome Trust Centre, University of Cape Town, Cape Town, South Africa
  10. Seattle Children’s Research Institute, University of Washington, Washington, USA
  11. Famcru, University of Stellenbosch, Cape Town, South Africa
  12. Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa
  13. Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa
  14. Centre for the AIDS Programme of Research in South Africa, Durban, South Africa
  15. National Health Laboratory Service, Cape Town, South Africa
  16. Central Clinical School, Monash University, Melbourne, Australia

Background: Young South African women are at disproportionate risk of bacterial vaginosis (BV) and HIV infection, and strategies to reduce these outcomes are urgently needed. Cervicovaginal Lactobacillus species such as L. crispatus protect against HIV, while L. iners is considered less protective. To understand this difference, this study compared the protein and functional profiles of cervicovaginal L. iners and L. crispatus communities in young South African women.

Methods: Vaginal swab samples collected from women (aged 16-22 years) with cervicovaginal microbiota dominated by either L. crispatus (n=19) or L. iners (n=50), were analysed using liquid chromatography-tandem mass spectrometry, a custom cervicovaginal database and MaxQuant. Data analysis comprised moderated t-tests, principal component analysis and hierarchical clustering.

Results: A total of 218 L. iners and 276 L. crispatus proteins were identified, and of the 105 proteins shared by both species, 39 were significantly differentially abundant. Proteins including glucose-6-phosphate isomerase and LPXTG-motif anchor-domain protein were overabundant in L. crispatus communities, and enolase and L-lactate dehydrogenase overabundant in L. iners. Comparison of L. iners protein relative abundance between BV positive versus negative women revealed that several L. iners proteins involved in pathogenesis and carbohydrate metabolism were significantly upregulated in women with non-optimal microbiota. Additionally, 40 host proteins were overabundant in women with L. iners and 13 in those with L. crispatus. After excluding participants with BV, L. iners dominance was correlated with immune markers (IgG H chain, clusterin and calpain small-subunit 1), while L. crispatus cytokeratin-8 overabundance suggests greater epithelial barrier integrity.

Discussion: Metaproteomic analyses provided valuable insight into the function of Lactobacillus spp. in vivo, demonstrating significant differences in the metabolic activities of L. iners versus L. crispatus. The functional activities of L. iners were linked to host BV status, suggesting that bacterial gene expression is influenced by environmental factors or strain level differences.