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Simone Webb Bench B 02/09/2016

Classification

Higher order taxa

Bacteria – Bacteria – Bacteroidetes – Flavobacteria – Flavobacteriaceae – Flavobacteriaceae – Capnocytophaga

Species

Capnocytophaga gingivalis Type strain is 27, as discovered by Leadbetter at al, 1979

Description and significance

http://www.antimicrobe.org/b92.asp#r19

Capnocytophaga gingiva is a gram negative, mesophilic and non-sporulating rod-shaped bacteria implicated in opportunistic periodontal disease (Leadbetter at al, 1979, antimicrobe). In 1979, Leadbetter et al proposed the genus ‘Capnocytophaga’, to include three morphologically and physiologically distinct species: Capnocytophaga ochracea, Capnocytophaga gingivalis and Capnocytophaga sputigena. The Capnocytophaga are gliding bacteria which constituted a predominant part of the cultivatable microbiota isolated from the gum in the Leadbetter et al study. The ability to attack polysaccharides and their capnophilic CO2-dependent growth (optimum growth in enrichment of carbon dioxide at 5-10%) influenced the naming of ‘Capnocytophaga’. ‘Gingivalis’ further refers to the fact that C. gingivalis are found on gingival crevices in the human oral cavity. C. gingivalis is clinically significant due to its ability to systemically spread from biofilm in the human oral microbiome to the blood, where it is most recently implicated in COPD and bacteraemia (jiang nd Ehrmann 16).

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Genome structure

https://www.ncbi.nlm.nih.gov/genome/?term=txid553178[Organism:noexp] http://www.biocyc.org/CGIN553178-HMP/NEW-IMAGE?type=GENOME-OVERVIEW&object=NIL&chromosome=NZ_ACLQ01000019 The ATCC 33624 strain of Capnocytophaga gingiva was shotgun sequenced and submitted to NCBI as a reference for the Human Microbiome Project in 2009. ATCC 33624 has a 2.67 Mb genome which consists of 2,507 genes coding for: 2,364 proteins, 8 rRNA’S, 47 tRNA’s, 1 ‘other’ RNA and 87 pseudogenes.

Cell structure and metabolism

http://www.kegg.jp/kegg-bin/highlight_pathway?scale=1.0&map=col00010&keyword=glycolysis http://www.kegg.jp/kegg-bin/highlight_pathway?scale=1.0&map=col00190&keyword=oxidative%20phosphorylation

C. gingiva are gram negative, short, rod-shaped cells, with a size of around 0.42-0.6 by 2.5 - 5.7 µm (Leadbetter at al). Colonies of C. gingiva are flat, thin, slightly yellow/pink and were seen by Leadbetter at al to have ‘uneven edges’ with ‘finger-like’ projections and growth spread far, even centimetres, away from the initial inoculation site on the agar media. Colonies of C. gingiva are found to have gliding motility across agar media, despite not possessing flagella (Leadbetter at al, antimicrobe).

C. gingiva possess all genes needed for glycolysis but are unable to undertake complete oxidative phosphorylation, as seen by the lack of NADH dehydrogenase, cytochrome bc1 and cytochrome c oxidase in its ‘KEGG’ metabolic pathway. However, all genes encoding the bacterial F-type ATP-ase subunits are present, suggesting that the ATP-ase gene product is now non-functional and that it is fermentative. As strictly fermentative chemoorganotrophic facultative anaerobes, C. gingiva preferentially ferment compounds such as glycogen or starch to produce acidic end products, e.g., acetate and succinate. (Leadbetter at al, 1979). Metabolism is rapid in aerobic conditions and can still occur in anaerobic conditions provided there are elevated CO2 levels (Leadbetter at al, 1979).

Ecology

http://www.antimicrobe.org/b92.asp#r19 microbe/host interactions.

C. gingiva is a facultative anaerobe which has been isolated in supragingival plaque, where it constitutes a part of the normal human oral microbiota (antimicrobe). It’s location in supragingival biofilms indicate potential presence in periodontal lesions, where it acts as an opportunistic pathogen, leading to systemic infection (Leadbetter at al, 1979, piau). Adhesins have also been described which allow aggregation of C. gingivalis with other oral bacteria to form a biofilm on the gingiva (poirier).

Pathology

In the study by Haffagee et al, 2009, teeth with high plaque mass contained more C. gingiva, which was isolated in 14% of over-60s with root caries. Regardless of this correlation between C. gingiva and plaque/dental caries, recent microbiome analysis suggests no link between C. gingiva and childhood dental caries. When normal mucosal barriers in the human oropharynx undergoes trauma, disease or ulceration, C. gingivalis can act as an opportunistic pathogen and upregulate genes responsible for the invasive pathogenesis. Periodontitis, causing chronic inflammation, has also been suggested to promote colonisation by antibiotic resistant resident C. gingiva bacteria (ehrmann 2013). Capnocytophaga species, once invasive, are able to cause serious systemic infections such as bacteraemia, endocarditis and lung infections in immunocompromised cancer patients (jiang, baquero, baranda, chan). A significant number of C. gingiva systemic infections are polymicrobial.

Application to biotechnology

A 2013 study by Ehrmann et al collected 48 subgingival isolates of human oral Capnocytophaga from both healthy and ill patients. In this study, no C. gingivalis was isolated from haematology patients, only from periodontist patients and healthy volunteers, confirming C. gingiva makes up a part of the healthy human oral microbiota. Of the 48 Capnocytophaga isolates, 44% had beta lactam resistance genes, and 29% had macrolide-lincosamide-streptogramin (MLS) resistance genes. In contrast, 11% of C. gingiva isolates had beta lactam resistance genes, and 16% had MLS resistance genes. Considering this study, C. gingivalis and related species are a significant reservoir of beta lactams and MLS antibiotic resistance genes. Exploiting the pathway related to antibiotic synthesis could be a future focus for biotechnology, however, other species of Capnocytophaga such as C. ochracea may be more useful in this respect.

Current research

A case study and review by Ehrmann et al in 2016 investigated the molecular mechanism for fluoroquinolone resistance in C. gingivalis, first described by Geisler et al in 2001. It was found that DNA gyrase (GyrA) was the primary target for fluoroquinolones in gram negative bacteria. The presumed gyrA quinolone-resistance-determining-region (QRDR) of C. gingivalis was determined, and a Gly80Asn mutation within the QRDR was found in a fluoroquinolone resistant C. gingivalis isolate, supporting the QRDR location. This review also highlighted the case of a multidrug resistant strain of C. gingivalis, which acquired resistance to third generation cephalosporins, MLS and fluoroquinolones. Further research is recommended to evaluate the frequency of the Gly80Asn QRDR mutation in response to selection pressure.

References

References examples

1. Sahm, K., MacGregor, B.J., Jørgensen, B.B., and Stahl, D.A. (1999) Sulphate reduction and vertical distribution of sulphate-reducing bacteria quantified by rRNA slotblot hybridization in a coastal marine sediment. Environ Microbiol 1: 65-74.

2. Human Oral Microbiome

This page is written by <Simone Webb> for the MICR3004 course, Semester 2, 2016