Prevotella intermedia

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1. Classification

a. Higher order taxa

Bacteria; Bacteroidetes; Bacteroidetes; Bacteroidales; Prevotellaceae; Prevotella intermedia (1)

2. Description and significance

Prevotella intermedia is a bacteria that previously went by the Genus name of Bacteroides. With advancements in DNA sequencing, researchers discovered that many bacteria previously classified as Bacteroides would be more appropriately fit for a new genus, Prevotella, due to their bile-sensitive characteristics. The genus Bacteroides was re-classified to contain bacteria that are bile-resistant gram-negative bacilli (2). One of only two stains of the entire Prevotella genus, among all species, that has had its entire DNA genome sequenced is P. intermedia (3). As with other pathogenic species of Prevotella, P. intermedia has been researched for its various pathogenic effects in humans. It is commonly studied for its role in the oral cavity, and more specifically, periodontal disease. P. intermedia is seen as the main cause of many periodontal diseases and is often hard to eliminate in infected areas, due to its ability to form biofilms. Its antibiotic-resistant capabilities have serious implications for human health (4). P. intermedia’s pathogenic impacts on human health are not yet fully understood.

3. Genome structure

Prevotella intermedia 17, a strain from the human periodontal pocket, was the first published genome sequence of Prevotella. Genes involved in P. intermedia’s cell envelope structure are highly conserved among multiple strains, including Prevotella intermedia 17. AdpB, a binding protein on the cell surface which is thought to be involved in the microbe’s adhesion capabilities, is highly conserved and found in all strains of P. intermedia (5). In the process of analyzing different strains of P. intermedia, scientists have found that only about 3% of the whole genome typically accounts for alignment between two strains. Despite the small percentage of alignment in nucleotide sequences, scientists found a 49Kb region where gene content is conserved and shared among the different genomes. Prevotella, as a genus, is reported to have roughly 165-170 core genes. P. intermedia’s core genes allow it to thrive in diverse environments (5).

4. Cell structure

Prevotella intermedia is an anaerobic, gram-negative, rod-shaped bacterium (6). P. intermedia is also classified as a black pigmented bacteria because of its formation of shiny and smooth colonies which appear either a grey, light brown, or black color on blood agar plates (7). P. intermedia has been found to possess exopolysaccharides which are composed of neutral sugars and mannose and are a major component of biofilm formation. These exopolysaccharides provide P. intermedia the ability to evade the innate human immune system (8).

5. Metabolic processes

P. intermedia is known as a periodontopathic bacteria whose metabolic activity often results in an accelerated development of oral biofilm-mediated diseases. P. intermedia metabolites are known to initiate and promote oral disease, both directly and indirectly (9). This bacterium is non-acid producing and utilizes amino acids and peptides as metabolic substrates. Fluoride is added into toothpastes in order to inhibit these metabolic substrates that result in disease (9). P. intermedia is known to metabolize glucose, allowing it to readily exist in the human oral cavity. Glucose metabolism utilizes the EMP pathway and hexokinase, which tends to increase the anaerobic properties of the organism. P. intermedia also favors catabolizing nitrogenous compounds for energy sources (10).

6. Ecology

P. intermedia generally requires the organic compounds hemin and menadione to grow. Despite having specific growth requirements, Prevotella is found in diverse areas of the human body. These regions range from the human oral cavity to human feces (5). Because of intraspecies differences that exist among the Prevotella genus, it is capable of thriving in diverse environments (5). P. intermedia is an opportunistic pathogen, therefore it thrives in diseased sites of the human body and has varying levels of pathogenicity. Consequently, healthy areas have lower levels of degradative enzyme activity. P. intermedia strains contain virulence factors that allow them to accommodate needs in these environments (5).

7. Pathology

Prevotella intermedia has serious implications in the context of medical pathology for humans, as it has been found to be one of the leading causes of periodontal disease. Periodontal diseases affect over 15% of people in the United States alone (11). One common periodontal disease is periodontitis, which can cause subgingival plaque, tissue attachment loss, and probing depth beyond standard ranges (12). One of the main reasons why P. intermedia has such a virulent impact on the connective tissue of the mouth is because of the biofilm it is capable of creating. The biofilm is present within the oral cavity in what is known as plaque (13). If the plaque persists it may form abscesses that leave the body open to other infections, such as atherosclerotic vascular disease (14). It has been found that the biofilm created by P. intermedia can be difficult for innate defense mechanisms and prescribed antibiotics to penetrate (8). P. intermedia can be eliminated with antibiotics such as tetracycline, doxycycline, and ofloxacin if it is still in its planktonic form as it has not completed biofilm formation (15).

8. Current Research

Although still unsure of the exact reasoning behind it, researchers have found that women experience an increase in the prevalence and severity of gingival inflammation during pregnancy (16). Because of this, the associations between Prevotella intermedia and the increase in periodontal gingival inflammation in pregnant women warrants further attention. Researchers have discovered that the average number of P. intermedia was higher in pregnant women compared to non-pregnant women in at subgingival plaque and saliva samples. Levels of P. intermedia were seen to increase throughout pregnancy. The growth of P. intermedia was almost twice as high in the second trimester of pregnancy than it was during the first trimester (17) and peaked during the third trimester (18). There was also an increase in P. intermedia directly following delivery. These levels were seen to remain elevated during lactation, however, they decreased to the same level as non-pregnant women after lactation discontinued (17). The presence of P. intermedia was also positively correlated with increased sex-hormone levels during pregnancy and an increase in the prevalence of other gingival pathogens throughout pregnancy (18). Because of P. intermedia’s negative implications for dental health and its perceived increase in prevalence throughout pregnancy the relationship between P. intermedia and pregnancy is an area of further interest that is currently being investigated by researchers.

Additional current research looks into the relationship between food extracts consumed and prevalence of P. intermedia. Some researchers argue that toothpastes and mouthwashes are the most feasible and effective methods in controlling prevotella biomass build-up in the oral cavity, and further emphasize the need for additional modes of bacterial regulation. A study was done on the influence of both mushroom and chicory extracts on the prevalence of P. intermedia biomass within the oral cavity, arguing that these extracts can act as natural antibacterial and antiplaque agents (19). Using scanning electron microscopy (SEM), the researchers found that DNA synthesis for P. intermedia was inhibited with the usage of either extract, indicating that the extracts do indeed work as antibacterials. Further research should look into the incorporation of natural extracts into cosmetic products to decrease the prevalence of harmful bacteria such as P. intermedia. More thorough education would be useful in developing countries in regards to which foods contain these natural antibacterials, in order to administer them in smaller doses.

9. References

1. Hahnke, et al. (2016). Taxonomy of the Genus Prevotella intermedia. Names for Life. doi:10.1601/tx.8042

2. Somer, H. J., and Summanen, P. (2002). Recent Taxonomic Changes and Terminology Update of Clinically Significant Anaerobic Gram-Negative Bacteria (Excluding Spirochetes). Clinical Infectious Diseases, 35(1): 17–21.

3. Sakamoto, M., and Ohkuma, M. (2012). Taxonomy of the Genus Prevotella. Names for Life. doi:10.1601/tx.80424.

4. Moon, J.-H., Kim, M., and Lee, J.-H. (2016). Genome sequence of Prevotella intermedia SUNY aB G8-9K-3, a biofilm forming strain with drug-resistance. Brazilian Journal of Microbiology, 48(1): 5–6.

5. Ruan, Y., Shen, L., Zou, Y., Qi, Z., Yin, J., Jiang, J., Guo, L., He, L., Chen, Z., Tang, Z., and others. (2015). Comparative genome analysis of Prevotella intermedia strain isolated from infected root canal reveals features related to pathogenicity and adaptation. BMC Genomics. 16(122): 1-21.

6. Roux, V., Robert, C., and Raoult, D. (2014). Non-contiguous finished genome sequence of Prevotella timonensis type strain 4401737T. Standards in Genomic Sciences, 9(3): 1346–1353.

7. Shah, H.N., and Collins, D.M. (1990). Prevotella, a new genus to include bacteroides melaninogenicus and related species formerly classified in the genus bacteroides. International Journal of Systematic and Evolutionary Microbiology. 40(2): 205-208.

8. Yamanaka, T., Furukawa, T., Matsumoto-Mashimo, C., Yamane, K., Sugimori, C., Nambu, T., Mori, N., Nishikawa, H., Walker, C.B., Leung, K.P., and others. (2009). Gene expression profile and pathogenicity of biofilm-forming Prevotella intermedia strain 17. BMC Microbiology, 9(11).

9. Ishiguro, K., Washio, J., Sasaki, K., and Takahashi, N. (2015). Real-time monitoring of the metabolic activity of periodontopathic bacteria. Journal of Microbiological Methods, 115(C): 22–26.

10. Takahashi, N., and Yamada, T. (2000). Glucose metabolism by Prevotella intermedia and Prevotella nigrescens - Molecular Oral Microbiology. Molecular Oral Microbiology. 15(3):188-195.

11. Dorn, B. R., Leung, K.-P., and Progulske-Fox, A. (1998). Invasion of Human Oral Epithelial Cells by Prevotella intermedia. Infection and Immunity, 66(12): 6054–6057.

12. Eke, P.I., Dye, A.B, Wei, L., Thorton-Evans, G.O., Genoco, R.J, Beck, J., Douglass, G., and Page, R. (2012). Prevalence of Periodontitis in Adults in the United States: 2009 and 2010. Journal of Dental Research, 91(10): 914–920. doi:10.1177/0022034512457373

13. Chandki, R., Banthia, P., and Bathia, R. (2011). Biofilms: A microbial home. Journal of Indian Society of Periodontology, 15(2): 111–114.

14. How, K. Y., Song, K. P., and Chan, K. G. (2016). Porphyromonas gingivalis: An Overview of Periodontopathic Pathogen below the Gum Line. Frontiers in Microbiology, 7(53): 1-14. doi:10.3389/fmicb.2016.00053

15. Takahashi, N., Ishihara, K., Kimizuka, R., Okuda, K., and Kato, T. (2006). The effects of tetracycline, minocycline, doxycycline and ofloxacin on Prevotella intermedia biofilm. Oral Microbiology and Immunology, 21(6): 366–371.

16. Wu, M., Chen, S., and Jian, S. (2015). Relationship between gingival inflammation and pregnancy. Mediators in Inflammation. (1): 1-11.

17. Gursoy, M., Haraldsson, G., Hyvonen, M., Sorsa, T., Pajukanta, R., and Kononen, E. (2009). Does the frequency of Prevotella intermedia increase during pregnancy? Oral Microbiology Immunity, (24): 299-303.

18. Carrillo-de-Albornoz, A., Figuero, E., Herrera, D., and Bascones-Martinez, A. (2010). Gingival changes during pregnancy: II. Influence of hormonal variations on the subgingival biofilm. Journal of Clinical Periodontology, 37(3): 230-240.

19. Signoretto, C., Marchi, A., Bertoncelli, A., Burlacchini, G., Tessarolo, F., Caola, I., Canepari, P. (2011). Effects of Mushroom and Chicory Extracts on the Physiology and Shape of Prevotella intermedia, a Periodontopathogenic Bacterium. Journal of Biomedicine and Biotechnology, 2011(2011): 1-9.