Inhibition of sialidase activity and cellular invasion by the bacterial vaginosis pathogen Gardnerella vaginalis

Govinden, Gemma; Parker, Jennifer; Naylor, Kathryn; Frey, Andrew; Anumba, Dilly; Stafford, Graham P.

doi:10.1007/s00203-018-1520-4

Cited by 32 publications

(36 citation statements)

References 37 publications

(76 reference statements)

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“…Similarly, the genomospecies had vastly different repertories of accessory genomes, except the group that contained GS05, GS04, and GS09. These differences may be important for adaptation to the vaginal microenvironment or BV pathology because some of the genes driving this difference include those known for virulence (e.g., sialidases) (44,45 ).…”

Section: Discussionmentioning

confidence: 99%

In Silico Analysis of Gardnerella Genomospecies Detected in the Setting of Bacterial Vaginosis

Potter¹,

Dantas

2019

Clinical Chemistry

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BACKGROUND Gardnerella vaginalis is implicated as one of the causative agents of bacterial vaginosis, but it can also be isolated from the vagina of healthy women. Previous efforts to study G. vaginalis identified 4 to 6 clades, but average nucleotide identity analysis indicates that G. vaginalis may be multiple species. Recently, Gardnerella was determined to be 13 genomospecies, with Gardnerella piottii, Gardnerella leopoldii, and Gardnerella swidsinkii delineated as separate species. METHODS We accessed 103 publicly available genomes annotated as G. vaginalis. We performed comprehensive taxonomic and phylogenomic analysis to quantify the number of species called G. vaginalis, the similarity of their core genes, and their burden of their accessory genes. We additionally analyzed publicly available metatranscriptomic data sets of bacterial vaginosis to determine whether the newly delineated genomospecies are present, and to identify putative conserved features of Gardnerella pathogenesis. RESULTS Gardnerella could be classified into 8 to 14 genomospecies depending on the in silico classification tools used. Consensus classification identified 9 different Gardnerella genomospecies, here annotated as GS01 through GS09. The genomospecies could be readily distinguished by the phylogeny of their shared genes and burden of accessory genes. All of the new genomospecies were identified in metatranscriptomes of bacterial vaginosis. CONCLUSIONS Multiple Gardnerella genomospecies operating in isolation or in concert with one another may be responsible for bacterial vaginosis. These results have important implications for future efforts to understand the evolution of the Gardnerella genomospecies, host–pathogen interactions of the genomospecies during bacterial vaginosis, diagnostic assay development for bacterial vaginosis, and metagenomic investigations of the vaginal microbiota.

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Section: Discussionmentioning

confidence: 99%

In Silico Analysis of Gardnerella Genomospecies Detected in the Setting of Bacterial Vaginosis

Potter¹,

Dantas

2019

Clinical Chemistry

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“…The involvement of Gardnerella sialidases in adhesion has not been demonstrated directly, although it has been reported that inhibition of sialidase activity in Gardnerella strain JCP8066 by an antiviral drug (Zanamavir) resulted in reduction of adherence to vaginal epithelial cells in vitro (12). Gardnerella spp.…”

Section: Characterization Of a Poly-c Homopolymer In Nanh3mentioning

confidence: 99%

Slipped strand mispairing in the gene encoding sialidase NanH3 inGardnerellaspp

Kurukulasuriya

Patterson

Hill

2020

Preprint

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Cell wall proteins with sialidase activity are involved in carbohydrate assimilation, adhesion to mucosal surfaces, and biofilm formation. Gardnerella spp. inhabit the human vaginal microbiome and encode up to three sialidase enzymes, two of which are cell wall associated. Here we demonstrate that the gene encoding extracellular sialidase NanH3 is found almost exclusively in G. piotii and closely related Gardnerella genome sp. 3, and its presence correlates with sialidase positive phenotype in a collection of 112 Gardnerella isolates. The nanH3 gene sequence includes a homopolymeric repeat of cytosines that varies in length within cell populations, indicating that this gene is subject to slipped-strand mispairing, a mechanisms of phase variation in bacteria. Variation in the length of the homopolymer sequence results in encoding of either the full length sialidase protein or truncated peptides due to introduction of reading-frame shifts and premature stop codons. Phase variation in this extracellular, cell wall associated sialidase may be involved in immune evasion or modulation of adhesion to host epithelial cells, and formation of biofilms characteristic of the vaginal dysbiosis known as bacterial vaginosis.

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“…Metabolomics combined with proteomic approaches represents one of the most important postgenomic analyses to investigate changes in cell metabolism and identify biomarkers during the course of infection inside macrophages (Singh et al, 2015 ). Several studies have demonstrated an association between host cell metabolism and response to different pathogens, including Leishmania (Lamour et al, 2012 ; Govinden et al, 2018 ; Price et al, 2018 ; Reddy et al, 2018 ).…”

Section: Proteomic Contribution To Understanding the Macrophage Respomentioning

confidence: 99%

In Search of Biomarkers for Pathogenesis and Control of Leishmaniasis by Global Analyses of Leishmania-Infected Macrophages

Veras¹,

Ramos²,

Menezes

2018

Front. Cell. Infect. Microbiol.

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Leishmaniasis is a vector-borne, neglected tropical disease with a worldwide distribution that can present in a variety of clinical forms, depending on the parasite species and host genetic background. The pathogenesis of this disease remains far from being elucidated because the involvement of a complex immune response orchestrated by host cells significantly affects the clinical outcome. Among these cells, macrophages are the main host cells, produce cytokines and chemokines, thereby triggering events that contribute to the mediation of the host immune response and, subsequently, to the establishment of infection or, alternatively, disease control. There has been relatively limited commercial interest in developing new pharmaceutical compounds to treat leishmaniasis. Moreover, advances in the understanding of the underlying biology of Leishmania spp. have not translated into the development of effective new chemotherapeutic compounds. As a result, biomarkers as surrogate disease endpoints present several potential advantages to be used in the identification of targets capable of facilitating therapeutic interventions considered to ameliorate disease outcome. More recently, large-scale genomic and proteomic analyses have allowed the identification and characterization of the pathways involved in the infection process in both parasites and the host, and these analyses have been shown to be more effective than studying individual molecules to elucidate disease pathogenesis. RNA-seq and proteomics are large-scale approaches that characterize genes or proteins in a given cell line, tissue, or organism to provide a global and more integrated view of the myriad biological processes that occur within a cell than focusing on an individual gene or protein. Bioinformatics provides us with the means to computationally analyze and integrate the large volumes of data generated by high-throughput sequencing approaches. The integration of genomic expression and proteomic data offers a rich multi-dimensional analysis, despite the inherent technical and statistical challenges. We propose that these types of global analyses facilitate the identification, among a large number of genes and proteins, those that hold potential as biomarkers. The present review focuses on large-scale studies that have identified and evaluated relevant biomarkers in macrophages in response to Leishmania infection.

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Inhibition of sialidase activity and cellular invasion by the bacterial vaginosis pathogen Gardnerella vaginalis

Cited by 32 publications

References 37 publications

In Silico Analysis of Gardnerella Genomospecies Detected in the Setting of Bacterial Vaginosis

In Silico Analysis of Gardnerella Genomospecies Detected in the Setting of Bacterial Vaginosis

Slipped strand mispairing in the gene encoding sialidase NanH3 inGardnerellaspp

In Search of Biomarkers for Pathogenesis and Control of Leishmaniasis by Global Analyses of Leishmania-Infected Macrophages

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