Cellerant Best of Class Technology Award

June 2017
Volume 13, Issue 6

Peer-Reviewed

Understanding the Oral Micronome

Bacterial Considerations in Dentistry

Betsy Reynolds, RDH, MS

How many types of bacteria exist in the oral micronome is debatable, but estimates range from hundreds and to even thousands of diverse organisms that select the oral cavity and periodontal tissues as their desired niches. Understanding the impact of bacteria on oral health is critical for the dental professional who wishes to deliver comprehensive preventive therapy. Pathogenic bacterial infections that cause oral inflammation have been linked to numerous systemic infections—making control of unresolved carious lesions and periodontal diseases even more crucial. Two species of bacteria that are especially noteworthy to oral healthcare providers are Streptococcus mutans and Porphyromonas gingivalis. Understanding their structure, function, and unique abilities is pivotal in designing therapeutic modalities and treatment strategies.

Structure of Bacterial Cells

Bacteria are prokaryotic cells, which are single-celled organisms without a nucleus or other membrane-bound organelles. This lack of a nucleus and organelles differentiates prokaryotes from eukaryotes, such as yeasts, plants, insects, and mammals. In contrast to nucleus-containing eukaryotic cells, the genetic material in prokaryotic cells is restricted to an area of the cytoplasm called the nucleoid.

Another structure found in prokaryotes but not in eukaryotic cells is the cell wall. Among its functions, the cell wall provides overall strength to the cell, maintains cell shape, and protects the bacterial cell from osmotic lysis. Additionally, the cell wall can protect against the entry of toxins into the bacterial cytoplasm. It is important for healthcare providers to understand the bacterial cell wall’s relationship to bacterial pathogenicity. The presence of a cell wall in prokaryotes continues to give rise to the advancement of treatment modalities (such as antibiotic therapy) that target bacterial cell wall integrity.

Prokaryotic cell wall structure differs between bacterial species based on their complexity and components. “Gram staining” is used to determine the chemical make-up of the cell wall, identifying bacteria as either Gram-positive or Gram-negative based on cell wall structure. Both cell wall types contain peptidoglycan (also known as murein)—a substance that has only been observed in the cell walls of bacteria. In addition to peptidoglycan, the cell walls of both Gram-negative and Gram-positive organisms contain other unique elements, which lends to the complexity and uniqueness between bacterial species. These structural differences must be kept in mind when developing specific treatment modalities to minimize inflammation and treat bacterial infections.

Gram-Positive Bacteria

The cell walls of Gram-positive bacteria are composed predominantly of layers of peptidoglycan, which can constitute up to 90% of the cell wall. In addition to peptidoglycan, Gram-positive cell walls contain teichoic acid embedded within the peptidoglycan layers. Teichoic acid is responsible for the rigidity of the cell wall and may also participate in bacterial cell division. Wall teichoic acids (WTAs) and their substituents play a role in bacterial cell surface charge and hydrophobicity. These dynamics affect the binding of extracellular molecules and play a role in protecting bacteria from negative environmental factors, such as high temperatures, elevated salt concentrations, and resistance to β-lactam antibiotics.1,2 Because WTAs are involved in cell adhesion and required for host infection, their role(s) in host disease and biofilm formation are currently being elucidated.3 As virulence factors (establishing and spreading infection in a host), WTAs may be key to developing therapeutics to address resistant bacterial infections.1 In the dental field, targeting WTAs may prove beneficial in limiting oral biofilm formation by Gram-positive organisms.

Gram-Negative Bacteria

The cell walls of Gram-negative bacteria are more complex in structure than those of Gram-positive organisms. Peptidoglycan makes up only a few layers of the cell wall, representing 5-10% of the total cell wall structure. Relatively thin, the cell wall contains no teichoic acids and significantly less peptidoglycan. Notably, the Gram-negative bacterial cell wall consists of an outer membrane (outside the peptidoglycan layer) that includes the component lipopolysaccharide (“LPS” or “endotoxin”).4 While the outer membrane functions primarily as a barrier to permeability, because of its lipopolysaccharides, it demonstrates several important features. Bacterial lipopolysaccharides are toxic in humans and have been shown to induce fever, activate the complement cascade (causing inflammation), and trigger blood factors (causing intravascular coagulation and hemorrhage). Intraoral infections by Gram-negative bacteria routinely present as inflammatory conditions affecting the periodontium.

Specific Oral Pathogens

As mentioned previously, the oral cavity is home to a diverse population of bacterial species. Many of these organisms are non-pathogenic and confer health benefits to the host. Commensal (non–disease causing) microbes provide a mutually beneficial relationship with host tissues. The oral tissues of the host provide a colonization surface for the commensals, and the bacteria provide “colonization resistance” against pathogenic, harmful organisms. In addition, commensal bacteria in plaque contribute to the development of a normal immune system by constantly providing a variety of bacterial antigens for the host’s innate immune system. By controlling the overgrowth of oral pathogenic bacteria, commensal populations can thrive and confer a myriad of health benefits to the host. Probiotic therapies designed to minimize the colonization of oral pathogens such as Streptococcus mutans and Porphyromonas gingivalis are currently being investigated.

Streptococcus mutans

Streptococcus mutans (S. mutans) is part of a group of seven closely related species (the “mutans streptococci”). Long implicated as a primary etiologic factor for dental caries, this organism is classified as a collective of Gram-positive, facultative anaerobes. As a facultative anaerobe, S. mutans is able to shift between aerobic and anaerobic respiration, adjusting to the amount of oxygen and fermentable material present. This allows the organism to reside in the biofilm or on exposed tooth surfaces. When S. mutans is involved, factors such as adherence to enamel, production of acidic metabolites, and the ability to synthesize extracellular polysaccharides contribute to producing caries.

Besides dental caries, S. mutans has been linked to other systemic disease processes. The bacteria can cause endocarditis, and research has demonstrated that it is a leading cause of this condition. Additionally, an intensive review exploring the virulence potential of S. mutans found that certain strains may aggravate ulcerative colitis and be a factor in its pathogenesis.5 The same study group found direct evidence of uptake of S. mutans by hepatocytes. As most liver cells are hepatocytes, bacterial uptake by hepatocytes may be a critical aspect in prompting further inflammatory responses.

The ramifications of these findings are enormous for the dental community. Resolution of caries, nutritional counseling, and appropriate home care therapy options designed to minimize caries formation should be prescribed for patients at risk to reduce the systemic and oral complications from S. mutans infection.

Porphyromonas gingivalis

Periodontal diseases are oral inflammatory infections produced by oral pathogens that survive as complex biofilms on tooth surfaces and in subgingival spaces. If these infections are not controlled, the collagenous supporting tissues of the periodontium may be destroyed. The effects of these diseases can range from mild, reversible inflammation to loss of teeth. Research has demonstrated that, of more than 500 bacterial species in human subgingival plaque, Porphyromonas gingivalis (P. gingivalis), a Gram-negative anaerobic bacterium, is the most significant etiologic agent in chronic periodontitis.6

Most strains of P. gingivalis possess fimbriae: thin, proteinaceous, 3–25 μm surface appendages that extend from the outer membrane of a bacterial cell. The presence of these specialized fimbriae allows the bacterium to adhere to both tissue and tooth surfaces in the subgingival spaces, which are ideally suited for this anaerobic microbe. Additionally, the fimbriae allow P. gingivalis to attach to other bacteria, which serves to increase the mass of subgingival plaque and protect this obligate anaerobe in the process. Once located in the subgingival niche, P. gingivalis is capable of breaking down the collagenous fibers that make up the periodontal ligament by inciting the inflammatory process through the generation of several virulence factors. One virulence factor of P. gingivalis worth noting is the microbe’s ability to make collagenase—an enzyme designed to break down collagen. Because of their strong anti-inflammatory and anti-collagenase properties, tetracyclines have long been used as an adjunct to periodontal therapy.

As a successful colonizer of the oral epithelium, P. gingivalis seems to be a highly adapted pathogen of the oral microbiome. Research endeavors elucidating systemic disease links to P. gingivalis infections have tended to focus on the possible direct and indirect influence the bacteria has on diseases such as atherosclerosis and rheumatoid arthritis.7 Interestingly, researchers at the University of Louisiana demonstrated that the presence of P. gingivalis was associated with changes in cancer cell differentiation, metastasis, and overall patient survival rate for esophageal squamous cell carcinoma (ESCC). Whether ESCC cells allow P. gingivalis to thrive or P. gingivalis infection promotes esophageal cancer remains to be clarified, but researchers are hopeful that these findings could be of benefit to those at risk for ESCC. In a statement, study investigator Huizhi Wang noted that “these findings provide the first direct evidence that P. gingivalis infection could be a novel risk factor for ESCC and may also serve as a prognostic biomarker for this type of cancer. It would suggest that improving oral hygiene may reduce ESCC risk; screening for P. gingivalis in dental plaque may identify susceptible subjects; and using antibiotics or other anti-bacterial strategies may prevent ESCC progression.”8

Conclusion

Caries control and treatment to prevent oral inflammation remains a priority for the dental profession. Understanding the microbial dynamics behind inflammatory conditions affecting the oral cavity will lead to treatment strategies designed to minimize the detrimental effects of oral diseases. As our understanding of the oral micronome continues to expand, in-office and at-home procedures will evolve to benefit from this knowledge.

References

1. Brown S, Santa Maria JP Jr, Walker S. Wall teichoic acids of gram-positive bacteria. Annul Review Microbiol. 2013; 67:313-336.

2. Bruslind L. Bacterial cell walls. In: Bruslind L. Microbiology. Pressbooks for Oregon State University. https://openoregonstate.pressbooks.pub/microbiology/. Accessed May 1, 2017.

3. Swoboda JG, Campbell J, Meredith TC, Walker S. Wall teichoic acid function, biosynthesis, and inhibition. Chembiochem. 2010;11(1):35-45.

4. Todar K. Structure and function of bacterial cells. In: Todar K. Todar’s Online Textbook of Microbiology. University of Wisconsin. 2008-2013. http://textbookofbacteriology.net/. Accessed May 1, 2017.

5. Kojima A, Nakano K, Wada K, et al. Infection of specific strains of Streptococcus mutans, oral bacteria, confers a risk of ulcerative colitis. Sci Rep. 2012;2:332.

6.How KY, Song KP, Chan KG. Porphyromonas gingivalis: an overview of periodontopathic pathogen below the gum line. Front Microbiol. 2016;7(2):53.

7. Mysak J, Podzimek S, Sommerova P, et al. Porphyromonas gingivalis: major periodontopathic pathogen overview. J Immunol Res. 2014:476068. doi: 10.1155/2014/476068

8.Gao S, Li S, Ma Z, et al. Presence of Porphyromonas gingivalis in esophagus and its association with the clinicopathological characteristics and survival in patients with esophageal cancer. Infect Agent Cancer. 2016; 11(1):3.

About the Author

Betsy Reynolds, RDH, MS
Oral Biologist and Continuing Education Provider
Fibroblastic Productions
Boise, Idaho

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