Metatranscriptome analysis of the vaginal microbiota reveals potential mechanisms for protection against metronidazole in bacterial vaginosis

Deng, Zhi-Luo; Gottschick, Cornelia; Bhuju, Sabin; Masur, Clarissa; Abels, Christoph; Wagner-Doebler, Irene

doi:10.1101/248302

Cited by 12 publications

(18 citation statements)

References 62 publications

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“…Populations of bacterial species in vaginal communities are likely comprised of multiple strains. Previous studies of the vaginal microbiome have largely treated these species as singular genotypes 43 , although some more recent studies have examined intraspecies diversity in these communities 44,45 . Intraspecies diversity is important because it is likely to influence many properties of the communities including their temporal stability and resilience, as well as how they relate to host health.…”

Section: Discussionmentioning

confidence: 99%

A comprehensive non-redundant gene catalog reveals extensive within-community intraspecies diversity in the human vagina

et al. 2020

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Analysis of metagenomic and metatranscriptomic data is complicated and typically requires extensive computational resources. Leveraging a curated reference database of genes encoded by members of the target microbiome can make these analyses more tractable. In this study, we assemble a comprehensive human vaginal non-redundant gene catalog (VIRGO) that includes 0.95 million non-redundant genes. The gene catalog is functionally and taxonomically annotated. We also construct a vaginal orthologous groups (VOG) from VIRGO. The gene-centric design of VIRGO and VOG provides an easily accessible tool to comprehensively characterize the structure and function of vaginal metagenome and metatranscriptome datasets. To highlight the utility of VIRGO, we analyze 1,507 additional vaginal metagenomes, and identify a high degree of intraspecies diversity within and across vaginal microbiota. VIRGO offers a convenient reference database and toolkit that will facilitate a more in-depth understanding of the role of vaginal microorganisms in women's health and reproductive outcomes.

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Section: Discussionmentioning

confidence: 99%

A comprehensive non-redundant gene catalog reveals extensive within-community intraspecies diversity in the human vagina

et al. 2020

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“…Complementary ‐omic technologies aimed at evaluating the functional capacity of the microbiome, including metatranscriptomics and metaproteomics, offer further opportunities to expand our understanding of gene transcriptional activity and protein expression respectively in complex microbial communities inhabiting the human body. To date, metatranscriptomics with RNA‐seq has only been exploited in a handful of small studies of the vaginal microbiome . Vaginal bacterial metatranscriptome comparison between two women with BV and two healthy individuals indicated that in BV, L. iners increases transcription of cholesterol‐dependent cytolysin, genes involved in glycerol metabolism, and CRISPR‐related genes .…”

Section: Introductionmentioning

confidence: 99%

“…Vaginal bacterial metatranscriptome comparison between two women with BV and two healthy individuals indicated that in BV, L. iners increases transcription of cholesterol‐dependent cytolysin, genes involved in glycerol metabolism, and CRISPR‐related genes . Comparing the vaginal bacterial metatranscriptome in BV between metronidazole treatment responders and non‐responders, found that increased transcription of CRISPR‐Cas genes in G. vaginalis in non‐responders may mitigate treatment resistance . Metatranscriptomic analyses of cultured vaginal bacteria under different growth conditions may also provide important information.…”

Section: Introductionmentioning

confidence: 99%

The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women

et al. 2019

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Introduction Young women in sub‐Saharan Africa are disproportionately affected by HIV, accounting for 25% of all new infections in 2017. Several behavioural and biological factors are known to impact a young woman's vulnerability for acquiring HIV. One key, but lesser understood, biological factor impacting vulnerability is the vaginal microbiome. This review describes the vaginal microbiome and examines its alterations, its influence on HIV acquisition as well as the efficacy of HIV prevention technologies, the role of the rectal microbiome in HIV acquisition, advances in technologies to study the microbiome and some future research directions. Discussion Although the composition of each woman's vaginal microbiome is unique, a microbiome dominated by Lactobacillus species is generally associated with a “healthy” vagina. Disturbances in the vaginal microbiota, characterized by a shift from a low‐diversity, Lactobacillus ‐dominant state to a high‐diversity non‐ Lactobacillus ‐dominant state, have been shown to be associated with a range of adverse reproductive health outcomes, including increasing the risk of genital inflammation and HIV acquisition. Gardnerella vaginalis and Prevotella bivia have been shown to contribute to both HIV risk and genital inflammation. In addition to impacting HIV risk, the composition of the vaginal microbiome affects the vaginal concentrations of some antiretroviral drugs, particularly those administered intravaginally, and thereby their efficacy as pre‐exposure prophylaxis (PrEP) for HIV prevention. Although the role of rectal microbiota in HIV acquisition in women is less well understood, the composition of this compartment's microbiome, particularly the presence of species of bacteria from the Prevotellaceae family likely contribute to HIV acquisition. Advances in technologies have facilitated the study of the genital microbiome's structure and function. While next‐generation sequencing advanced knowledge of the diversity and complexity of the vaginal microbiome, the emerging field of metaproteomics, which provides important information on vaginal bacterial community structure, diversity and function, is further shedding light on functionality of the vaginal microbiome and its relationship with bacterial vaginosis (BV), as well as antiretroviral PrEP efficacy. Conclusions A better understanding of the composition, structure and function of the microbiome is needed to identify opportunities to alter the vaginal microbiome and prevent BV and reduce the risk of HIV acquisition.

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“…RNA from expressed genes is stronger evidence for functional activity than DNA, as many genes are only conditionally expressed. However, metatranscriptomic sequencing may not capture all species in the vaginal microbiome if some are insufficiently active at the time of sampling . Thus metatranscriptomic sequencing provides a census of who‐is‐active, rather than who‐is‐there, and an inventory of their transcriptionally active genes and pathways.…”

Section: Community Sequencing Methodsmentioning

confidence: 99%

“…Community sequencing is furthering the study of how BV‐associated microbes increase HIV and HPV risk and reduce efficacy of antiretrovirals for HIV prevention . Metatranscriptomic sequencing of the vaginal microbiome during BV and STI is being used to find pathways related to aetiology, treatment targets, and treatment evasion, as well as to determine the dominant pathogen in STI co‐infection …”

Section: Research In the Vaginal Microbiome Using Community Sequencingmentioning

confidence: 99%

Understanding and interpreting community sequencing measurements of the vaginal microbiome

Berman

McLaren

Callahan

2019

BJOG

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Community-wide high-throughput sequencing has transformed the study of the vaginal microbiome, and clinical applications are on the horizon. Here we outline the three main community sequencing methods: (1) amplicon sequencing, (2) shotgun metagenomic sequencing, and (3) metatranscriptomic sequencing. We discuss the advantages and limitations of community sequencing generally, and the unique strengths and weaknesses of each method. We briefly review the contributions of community sequencing to vaginal microbiome research and practice. We develop suggestions for critically interpreting research results and potential clinical applications based on community sequencing of the vaginal microbiome.

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Metatranscriptome analysis of the vaginal microbiota reveals potential mechanisms for protection against metronidazole in bacterial vaginosis

Cited by 12 publications

References 62 publications

A comprehensive non-redundant gene catalog reveals extensive within-community intraspecies diversity in the human vagina

A comprehensive non-redundant gene catalog reveals extensive within-community intraspecies diversity in the human vagina

The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women

Understanding and interpreting community sequencing measurements of the vaginal microbiome

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