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Impact of the mycobiome on the health of the female genital tract

The female genital tract microbiome comprises a community of microorganisms. Imbalances in the microbiome are associated with vaginal diseases such as bacterial vaginosis (BV) and sexually transmitted infections (STIs). These diseases greatly burden South Africa, and young women in this region are a...

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Main Author: Gangiah, Tamlyn Kirstey
Other Authors: Mulder, Nicola
Format: Thesis
Language:English
Published: Department of Clinical Laboratory Sciences 2023
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access_status_str Open Access
author Gangiah, Tamlyn Kirstey
author2 Mulder, Nicola
author_browse Gangiah, Tamlyn Kirstey
Mulder, Nicola
author_facet Mulder, Nicola
Gangiah, Tamlyn Kirstey
author_sort Gangiah, Tamlyn Kirstey
collection Thesis
description The female genital tract microbiome comprises a community of microorganisms. Imbalances in the microbiome are associated with vaginal diseases such as bacterial vaginosis (BV) and sexually transmitted infections (STIs). These diseases greatly burden South Africa, and young women in this region are at an increased risk of contracting vaginal diseases. Consequently, it is vital to investigate the factors that influence FGT health. The fungal constituent of the microbiome (the mycobiome) has been demonstrated to play a role in regulating mucosal health, especially when the bacterial component is disturbed. However, we have a limited understanding of the vaginal mycobiome since many microbiome studies have focused on bacterial communities and have neglected low abundance taxonomic groups, such as fungi. To reduce this knowledge deficit, we present the first large-scale metaproteomic study to define the taxonomic composition and potential functional processes of the vaginal mycobiome in South African women. We examined vaginal fungal communities present in optimal and nonoptimal states (BV, STIs, and genital inflammation) by collecting lateral vaginal wall swabs from 123 women for liquid chromatography-tandem mass spectrometry. Taxonomic analysis requires representative sequence databases; however, since mycobiome research is relatively new, fungal databases are still in their infancy. As a result, metaproteomic methods are not optimized for fungal research. Therefore, we optimized a metaproteomic approach to increase fungal protein group assignments. With this, 50 fungal proteins belonging to 39 different genera were identified post quality-control and analysed for taxonomic and functional distributions. Taxonomic analysis revealed that the vaginal mycobiome had a high relative abundance of Candida across optimal and non-optimal states. We observed changes in differential abundance at the genus and biological process level between optimal and non-optimal states for BV and Mycoplasma genitalium. In the BV positive state, most fungal proteins were significantly underabundant (p< 0.05) compared to the BV negative state, with the exception of Malassezia and Condiobolus. Correspondingly, Nugent score was negatively associated with total fungal protein intensity, implying that the microenvironment during BV is less suitable for fungal growth. Furthermore, we assessed which clinical variables were associated with driving fungal community composition; results indicated that Nugent score, pro-inflammatory cytokines, chemokines, vaginal pH, Chlamydia trachomatis, and the presence of clue cells were involved. Lastly, we used publicly available vaginal proteome data to confirm our fungal identifications and suspect Candida, Debaryomyces, Kluyveromyces, Malassezia, Penicillium, Yarrowia, Aspergillus, Cryptococcus, Wallemia, Trichosporon, and Saccharomyces are likely true vaginal inhabitants. Thus, this study sets the groundwork for understanding the vaginal mycobiome and its association with prevalent vaginal diseases.
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spelling oai:open.uct.ac.za:11427/37109 Impact of the mycobiome on the health of the female genital tract Gangiah, Tamlyn Kirstey Mulder, Nicola Masson, Lindi Bioinformatics The female genital tract microbiome comprises a community of microorganisms. Imbalances in the microbiome are associated with vaginal diseases such as bacterial vaginosis (BV) and sexually transmitted infections (STIs). These diseases greatly burden South Africa, and young women in this region are at an increased risk of contracting vaginal diseases. Consequently, it is vital to investigate the factors that influence FGT health. The fungal constituent of the microbiome (the mycobiome) has been demonstrated to play a role in regulating mucosal health, especially when the bacterial component is disturbed. However, we have a limited understanding of the vaginal mycobiome since many microbiome studies have focused on bacterial communities and have neglected low abundance taxonomic groups, such as fungi. To reduce this knowledge deficit, we present the first large-scale metaproteomic study to define the taxonomic composition and potential functional processes of the vaginal mycobiome in South African women. We examined vaginal fungal communities present in optimal and nonoptimal states (BV, STIs, and genital inflammation) by collecting lateral vaginal wall swabs from 123 women for liquid chromatography-tandem mass spectrometry. Taxonomic analysis requires representative sequence databases; however, since mycobiome research is relatively new, fungal databases are still in their infancy. As a result, metaproteomic methods are not optimized for fungal research. Therefore, we optimized a metaproteomic approach to increase fungal protein group assignments. With this, 50 fungal proteins belonging to 39 different genera were identified post quality-control and analysed for taxonomic and functional distributions. Taxonomic analysis revealed that the vaginal mycobiome had a high relative abundance of Candida across optimal and non-optimal states. We observed changes in differential abundance at the genus and biological process level between optimal and non-optimal states for BV and Mycoplasma genitalium. In the BV positive state, most fungal proteins were significantly underabundant (p< 0.05) compared to the BV negative state, with the exception of Malassezia and Condiobolus. Correspondingly, Nugent score was negatively associated with total fungal protein intensity, implying that the microenvironment during BV is less suitable for fungal growth. Furthermore, we assessed which clinical variables were associated with driving fungal community composition; results indicated that Nugent score, pro-inflammatory cytokines, chemokines, vaginal pH, Chlamydia trachomatis, and the presence of clue cells were involved. Lastly, we used publicly available vaginal proteome data to confirm our fungal identifications and suspect Candida, Debaryomyces, Kluyveromyces, Malassezia, Penicillium, Yarrowia, Aspergillus, Cryptococcus, Wallemia, Trichosporon, and Saccharomyces are likely true vaginal inhabitants. Thus, this study sets the groundwork for understanding the vaginal mycobiome and its association with prevalent vaginal diseases. 2023-03-02T08:12:55Z 2023-03-02T08:12:55Z 2022 2023-02-20T12:46:42Z Master Thesis Masters MSc http://hdl.handle.net/11427/37109 eng application/pdf Department of Clinical Laboratory Sciences Faculty of Health Sciences
spellingShingle Bioinformatics
Gangiah, Tamlyn Kirstey
Impact of the mycobiome on the health of the female genital tract
thesis_degree_str Master's
title Impact of the mycobiome on the health of the female genital tract
title_full Impact of the mycobiome on the health of the female genital tract
title_fullStr Impact of the mycobiome on the health of the female genital tract
title_full_unstemmed Impact of the mycobiome on the health of the female genital tract
title_short Impact of the mycobiome on the health of the female genital tract
title_sort impact of the mycobiome on the health of the female genital tract
topic Bioinformatics
url http://hdl.handle.net/11427/37109
work_keys_str_mv AT gangiahtamlynkirstey impactofthemycobiomeonthehealthofthefemalegenitaltract