Comparative genomics of human Lactobacillus crispatus isolates reveals genes for glycosylation and glycogen degradation: Implications for in vivo dominance of the vaginal microbiota

Veer, Charlotte van der; Hertzberger, Rosanne; Bruisten, Sylvia M.; Tytgat, Hanne L. P.; Swanenburg, Jorne; Angelino-Bart, Alie de Kat; Schuren, Frank; Molenaar, Douwe; Reid, Gregor; Vries, Henry De; Kort, Remco

doi:10.1101/441972

Cited by 22 publications

(40 citation statements)

References 50 publications

(51 reference statements)

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“…These families of vaginal orthologs will assist the development of a mechanistic understanding of these proteins and how they relate to health. For example, van der Veer and co-workers recently identified and characterized the L. crispatus pullulanase (pulA) gene which they show encodes an enzyme with amylase activity that likely allows this species to degrade host glycogen in the vaginal environment 42 . Using VIRGO, we were able to identify pullulanase domain containing proteins in 37 other vaginal taxa including: G. vaginalis, L. iners and P. timonensis ( Supplementary Data 12), providing insight into the breadth of vaginal bacteria that may be capable of degrading host glycogen.…”

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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“…In healthy women, lactic acid bacteria (LAB) are thought to be responsible for maintaining a homeostatic microbiome by inhibiting growth and adhesion of other microbes via the production of secreted metabolites such as lactic acid, biosurfactants, bacteriocins and H 2 O 2 . L. crispatus is a prevalent commensal of the healthy vaginal environment in various microbiome studies and produces both lactic acid and H 2 O 2 [18, 19]. Additionally, L. crispatus secretes the L-lactic acid isomer which has been extensively studied for its ability to lower vaginal pH, elicit anti-inflammatory responses and inhibit microbial colonisation [20, 21].…”

Section: Importancementioning

confidence: 99%

Recurrent Vulvovaginal Candidiasis; a dynamic interkingdom biofilm disease ofCandidaandLactobacillus

McKloud

Sherry

Kean

et al. 2021

Preprint

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Vulvovaginal Candidiasis (VVC) is the most prevalent Candida infection in humans affecting 75% of women at least once throughout their lifetime. In its debilitating recurrent form, RVVC is estimated to affect 140 million women annually. Despite this strikingly high prevalence, treatment options for RVVC remain limited with many women experiencing failed clinical treatment with frontline azoles. Further, the cause of onset and recurrence of disease is largely unknown with few studies identifying potential mechanisms of failed treatment. This study aimed to assess a panel of clinical samples from healthy women and those with RVVC to investigate the influence of Candida, vaginal microbiome and antagonism between Candida and Lactobacillus on disease pathology. 16S rRNA sequencing characterised disease by a reduction in specific health-associated Lactobacillus such as L. crispatus, coupled with an increase in L. iners. In vitro analysis showed Candida albicans clinical isolates are capable of heterogeneous biofilm formation and show the presence of hyphae and C. albicans aggregates in vaginal lavage. Additionally, the ability of Lactobacillus to inhibit C. albicans biofilm formation and biofilm-related geneexpression was demonstrated. Using RNA sequencing technology, we were able to exploit a possible mechanism by which L. crispatus may aim to re-establish a healthy vaginal environment through amino-acid acquisition from C. albicans. This study suggests RVVC is not entirely due to an arbitrary switch in C. albicans from commensal to pathogen and understanding interactions between the yeast and vaginal Lactobacillus species may be more crucial to elucidating the cause of RVVC and developing appropriate therapies.

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“…These families of vaginal orthologs will assist the development of a mechanistic understanding of these proteins and how they relate to health. For example, van der Veer and co-workers recently identified and characterized the L. crispatus pullulanase ( pulA ) gene which they show encodes an enzyme with amylase activity that likely allows this species to degrade host glycogen in the vaginal environment [52]. Using VIRGO and VOG, we were able to identify pullulanase domain containing proteins in 37 other vaginal taxa including: G. vaginalis, L. iners and P. timonensis ( Additional file 2: Table S12 ), providing insight into the breadth of vaginal bacteria that may be capable of degrading host glycogen.…”

Section: Discussionmentioning

confidence: 99%

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

Crabtree

Holm

et al. 2019

Preprint

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12 Background 13 Analysis of metagenomic and metatranscriptomic data is complicated and typically 14 requires extensive computational resources. Leveraging a curated reference database 15 of genes encoded by members of the target microbiome can make these analyses more 16 tractable. Unfortunately, there is no such reference database available for the vaginal 17 microbiome. 18 Results 19 In this study, we assembled a comprehensive human vaginal non-redundant gene 20 catalog (VIRGO) from 264 vaginal metagenomes and 416 genomes of urogenital 21 bacterial isolates. VIRGO includes 0.95 million non-redundant genes compiled from a 22 3 Keywords 39 vaginal microbiome, metagenome and metatranscriptome reference database, non-40 redundant gene catalog, intraspecies diversity, gene-centric design, protein family 41 catalog, multi-omics data integration 42 4 Background 43The microbial communities that inhabit the human body play critical roles in the 44 maintenance of health, and dysfunction of these communities is often associated with 45 disease [1]. Taxonomic profiling of the human microbiome via 16S rRNA gene amplicon 46 sequencing has provided critical insight into the potential role of the microbiota in a wide 47 array of common diseases [2][3][4]. Yet these data routinely fall short of describing the 48 etiology of such microbiome-associated diseases, such as bacterial vaginosis [5, 6], 49Crohn's disease [7, 8] or psoriasis [9], among others. This is perhaps because while 50 16S rRNA gene sequencing can provide species-level taxonomic profiles of a microbial 51 community, it does not describe the genes or metabolic functions that are encoded in 52 the constituents' genomes. This is an important distinction because strains of a bacterial 53 species have been documented to exhibit substantial diversity in gene content [10], 54 such that their genomes harbor sets of accessory genes whose presence is variable 55 [11, 12]. It is therefore difficult, if not impossible, to infer the complete function of a 56 microbial species in a specific environment using only the sequence of their 16S rRNA 57 gene. As a consequence, to investigate the role of the human microbiome in health and 58 diseases, particular emphasis should be placed on describing the gene content and 59 gene expression of these microbial communities. 60 61 Metagenomic and metatranscriptomic profiling are emerging approaches aimed at 62 characterizing the gene content and expression of microbial communities. Results have 63 led to increased appreciation for the important role microbial communities play in human 64 health and diseases [13, 14]. Despite the rapid development and increased throughput 65 of sequencing technologies, current knowledge of the genetic and functional diversity of 66 microbial community is still highly limited. This is due, at least in part, to a lack of 67 resources necessary for the analysis of these massive short read datasets [13, 15]. De 68 novo assembly of metagenomic or metatranscriptomic datasets typically requires rather 69 subst...

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Comparative genomics of human Lactobacillus crispatus isolates reveals genes for glycosylation and glycogen degradation: Implications for in vivo dominance of the vaginal microbiota

Cited by 22 publications

References 50 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

Recurrent Vulvovaginal Candidiasis; a dynamic interkingdom biofilm disease ofCandidaandLactobacillus

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

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