Publications by authors named "Mary Davey"

Article Synopsis
  • The COVID-19 pandemic continues despite widespread vaccination, emphasizing the need for new therapeutic and preventive strategies, particularly through exploring the oral microbiome's role in SARS-CoV-2 infection.
  • Research revealed that certain compounds from oral bacteria, such as phosphoglycerol dihydroceramide (PGDHC) and gingipains, can inhibit SARS-CoV-2 infection, while other unidentified factors may interfere with the virus's ability to fuse with host cells.
  • Variability in oral microbial communities among individuals means some saliva cultures can inhibit while others may enhance infection, highlighting the complex relationship between oral bacteria and COVID-19, and suggesting potential avenues for new treatment options.
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Article Synopsis
  • The type IX secretion system (T9SS) helps bacterial pathogens infect hosts, and its activation is regulated by a signaling cascade, with PorX being a key protein that could be targeted for drug development.
  • Structural analysis shows that PorX has a unique enzyme domain similar to alkaline phosphatase, indicating its involvement in previously unlinked nucleotide and lipid signaling pathways.
  • PorX acts as a zinc sensor and is crucial for the secretion of virulence factors in pathogenic bacteria, suggesting it could be an effective target for strategies to disrupt T9SS and reduce virulence.
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uses a variety of mechanisms to actively interact with and promote the hydrolysis of red blood cells (RBCs) to obtain iron in the form of heme. In this study, we investigated the function of lipoprotein PG1881 which was previously shown to be up-regulated during subsurface growth and selectively enriched on outer membrane vesicles (OMVs). Our results show that wildtype strain W83 formed large aggregates encompassing RBCs whereas the PG1881 deletion mutant remained predominately as individual cells.

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Article Synopsis
  • The Type-IX secretion system (T9SS) is a bacterial nanomachinery critical for the infection process, regulated by a signaling cascade led by the protein PorX, making it a potential target for drugs.
  • Research on PorX revealed it has a unique enzymatic domain similar to alkaline phosphatases, indicating it plays a role in nucleotide and lipid signaling that was previously unrecognized in the context of T9SS.
  • PorX exhibits zinc-dependent phosphodiesterase activity and can dimerize through a novel mechanism involving zinc, suggesting it's a cellular zinc sensor and further emphasizing its importance in virulence factor secretion in pathogenic bacteria.
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Article Synopsis
  • The study examines the role of the oral microbiome in SARS-CoV-2 infection, highlighting its potential in developing new COVID-19 treatments.
  • Researchers found that specific compounds like phosphoglycerol dihydroceramide (PGDHC) and gingipains significantly inhibit SARS-CoV-2 infection, with some bacteria inducing cytotoxic effects on infected cells.
  • The study reveals variability among individuals regarding how oral microbial communities can either inhibit or enhance SARS-CoV-2 infection, suggesting a complex interplay that could lead to innovative therapeutic strategies.
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Porphyromonas gingivalis, like other members of the phylum Bacteroidetes (synonym Bacteroidota), synthesizes several classes of dihydroceramides and peptidolipids. Using a similar strategy as that recently used to delimit the lipidome of its close relative Bacteroides fragilis, we applied linear ion trap multiple-stage mass spectrometry (linear ion trap MS) with high-resolution mass spectrometry, to structurally characterize the complete lipidome of P. gingivalis and compare it to B.

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The maintenance of diminished acid ceramidase (ASAH1) gene expression leading to the accumulation of antiproliferative intracellular ceramides in oral squamous cell carcinoma (OSCC) has emerged as a prospective oral cancer therapeutic regimen. Our published study demonstrated that the key periodontal pathogen Porphyromonas gingivalis downregulates the expression patterns of ASAH1 mRNA in normal epithelial cells in vitro. Therefore, P.

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Aims: Gingival crevicular fluid (GCF) constitutes the primary growth substrate for . The goal of this work was to evaluate the growth of different strains of on human serum albumin (HSA), a major constituent of GCF.

Methods: Growth of five different strains of in the HSA medium was examined and, surprisingly, three of the strains underwent autolysis within 24 h.

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Studies are showing that the stress hormone cortisol can reach high levels in the gingival sulcus and induce shifts in the metatranscriptome of the oral microbiome. Interestingly, it has also been shown that cortisol can influence expression levels of Type IX Secretion System (T9SS) genes involved in gliding motility in bacteria belonging to the phylum Bacteroidota. The objective of this study was to determine if cortisol impacts gene expression and surface translocation of strain W50.

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Like other members of the phylum , the oral anaerobe Porphyromonas gingivalis synthesizes a variety of sphingolipids, similar to its human host. Studies have shown that synthesis of these lipids (dihydroceramides [DHCs]) is involved in oxidative stress resistance, the survival of P. gingivalis during stationary phase, and immune modulation.

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The periodontal pathogen strain W83 displays at least three different surface glycans, specifically two types of lipopolysaccharides (O-LPS and A-LPS) and K-antigen capsule. Despite the importance of K-antigen capsule to the virulence of , little is known as to how expression of genes involved in the synthesis of this surface glycan is regulated. The genes required for K-antigen capsule synthesis are located in a locus that encodes a number of transcripts, including an operon (PG0104 to PG0121, generating ~19.

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Toll-like receptor 2 (TLR2) activation has been implicated in the pathogenesis of periodontal disease but the identity of the TLR2 agonists has been an evolving story. The serine/glycine lipids produced by are reported to engage human TLR2 and will promote the production of potent pro-inflammatory cytokines. This investigation compared the recovery of serine/glycine lipids in periodontal organisms, teeth, subgingival calculus, subgingival plaque, and gingival tissues, either from healthy sites or periodontally diseased sites.

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Periodontal diseases are chronic inflammatory diseases of the periodontium that result in progressive destruction of the soft and hard tissues supporting the teeth, and it is the most common cause of tooth loss among adults. In the US alone, over 100 million individuals are estimated to have periodontal disease. Subgingival bacteria initiate and sustain inflammation, and, although several bacteria have been associated with periodontitis, has emerged as the key etiological organism significantly contributing to the disease.

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Our understanding of how the oral anaerobe Porphyromonas gingivalis can persist below the gum line, induce ecological changes, and promote polymicrobial infections remains limited. P. gingivalis has long been described as a highly proteolytic and asaccharolytic pathogen that utilizes protein substrates as the main source for energy production and proliferation.

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To describe the factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mild-to-moderate patients attending for assessment. This observational study was conducted in a Model 4 tertiary referral center in Ireland. All patients referred for SARS-CoV-2 assessment over a 4-week period were included.

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Sphingolipids (SLs) are essential structural components of mammalian cell membranes. Our group recently determined that the oral anaerobe delivers its SLs to host cells and that the ability of to synthesize SLs limits the elicited host inflammatory response during cellular infection. As robustly produces outer membrane vesicles (OMVs), we hypothesized that OMVs serve as a delivery vehicle for SLs, that the SL status of the OMVs may impact cargo loading to OMVs, and that SL-containing OMVs limit elicited host inflammation similar to that observed by direct bacterial challenge.

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Many bacteria switch between a sessile and a motile mode in response to environmental and host-related signals. , an oral anaerobe implicated in the etiology of chronic periodontal disease, has long been described as a nonmotile bacterium. And yet, recent studies have shown that under certain conditions, is capable of surface translocation.

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Porphyromonas gingivalis is the only known human-associated prokaryote that produces a peptidylarginine deiminase (PPAD), a protein-modifying enzyme that is secreted along with a number of virulence factors via a type IX secretion system (T9SS). While the function of PPAD in P. gingivalis physiology is not clear, human peptidylarginine deiminases are known to convert positively charged arginine residues within proteins to neutral citrulline and, thereby, impact protein conformation and function.

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In order to persist, bacteria need to adjust their physiological state in response to external and internal cues. External stimuli are often referred to as stressors. The stringent response, mediated by the alarmone (p)ppGpp, is central to the stress response in many bacteria; yet, there is limited knowledge regarding the role of (p)ppGpp signaling in bacteria belonging to the phylum Bacteroidetes.

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Our understanding of how oral microbiota adapt in response to changes in their surroundings remains limited. This is particularly true of the slow-growing anaerobes that persist below the gum line. Here, we report that the oral anaerobe Porphyromonas gingivalis strain 381 can surface translocate when sandwiched between two surfaces.

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The asaccharolytic anaerobe metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins. Often, these proteins are protected by a diverse array of carbohydrates tethered to the polypeptide chain via glycolytic bonds, and produces enzymes capable of liberating these carbohydrates, exposing the proteinaceous core. In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.

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Oral squamous cell carcinomas are a major cause of morbidity and mortality, and tobacco usage, alcohol consumption, and poor oral hygiene are established risk factors. To date, no large-scale case-control studies have considered the effects of these risk factors on the composition of the oral microbiome, nor microbial community associations with oral cancer. We compared the composition, diversity, and function of the oral microbiomes of 121 oral cancer patients to 242 age- and gender-matched controls using a metagenomic multivariate analysis pipeline.

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Bacteria alter the biophysical properties of their membrane lipids in response to environmental cues, such as shifts in pH or temperature. In essence, lipid composition determines membrane structure, which in turn influences many basic functions, such as transport, secretion, and signaling. Like other members of the phylum Bacteroidetes, the oral anaerobe possesses the ability to synthesize a variety of novel membrane lipids, including species of dihydroceramides that are distinct, yet similar in structure to sphingolipids produced by the human host.

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Unlabelled: Bacterial cell surface glycans, such as capsular polysaccharides and lipopolysaccharides (LPS), influence host recognition and are considered key virulence determinants. The periodontal pathogen Porphyromonas gingivalis is known to display at least three different types of surface glycans: O-LPS, A-LPS, and K-antigen capsule. We have shown that PG0121 (in strain W83) encodes a DNABII histone-like protein and that this gene is transcriptionally linked to the K-antigen capsule synthesis genes, generating a large ∼19.

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The Chloride Intracellular Ion Channel (CLIC) family consists of six evolutionarily conserved proteins in humans. Members of this family are unusual, existing as both monomeric soluble proteins and as integral membrane proteins where they function as chloride selective ion channels, however no function has previously been assigned to their soluble form. Structural studies have shown that in the soluble form, CLIC proteins adopt a glutathione S-transferase (GST) fold, however, they have an active site with a conserved glutaredoxin monothiol motif, similar to the omega class GSTs.

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