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The Biology of

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  • Authors: J.A. Lemos1, S.R. Palmer2, L. Zeng3, Z.T. Wen4, J.K. Kajfasz5, I.A. Freires6, J. Abranches7, L.J. Brady8
  • Editors: Vincent A. Fischetti9, Richard P. Novick10, Joseph J. Ferretti11, Daniel A. Portnoy12, Miriam Braunstein13, Julian I. Rood14
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610; 2: Division of Biosciences, College of Dentistry, Ohio State University, Columbus, OH 43210; 3: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610; 4: Department of Comprehensive Dentistry and Biomaterials and Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112; 5: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610; 6: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610; 7: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610; 8: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610; 9: The Rockefeller University, New York, NY; 10: Skirball Institute for Molecular Medicine, NYU Medical Center, New York, NY; 11: Department of Microbiology & Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK; 12: Department of Molecular and Cellular Microbiology, University of California, Berkeley, Berkeley, CA; 13: Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC; 14: Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
  • Source: microbiolspec January 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0051-2018
  • Received 04 December 2018 Accepted 10 December 2018 Published 18 January 2019
  • J.A. Lemos, [email protected]
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  • Abstract:

    As a major etiological agent of human dental caries, resides primarily in biofilms that form on the tooth surfaces, also known as dental plaque. In addition to caries, is responsible for cases of infective endocarditis with a subset of strains being indirectly implicated with the onset of additional extraoral pathologies. During the past 4 decades, functional studies of have focused on understanding the molecular mechanisms the organism employs to form robust biofilms on tooth surfaces, to rapidly metabolize a wide variety of carbohydrates obtained from the host diet, and to survive numerous (and frequent) environmental challenges encountered in oral biofilms. In these areas of research, has served as a model organism for ground-breaking new discoveries that have, at times, challenged long-standing dogmas based on bacterial paradigms such as and . In addition to sections dedicated to carbohydrate metabolism, biofilm formation, and stress responses, this article discusses newer developments in biology research, namely, how interspecies and cross-kingdom interactions dictate the development and pathogenic potential of oral biofilms and how next-generation sequencing technologies have led to a much better understanding of the physiology and diversity of as a species.

  • Citation: Lemos J, Palmer S, Zeng L, Wen Z, Kajfasz J, Freires I, Abranches J, Brady L. 2019. The Biology of . Microbiol Spectrum 7(1):GPP3-0051-2018. doi:10.1128/microbiolspec.GPP3-0051-2018.

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/content/journal/microbiolspec/10.1128/microbiolspec.GPP3-0051-2018
2019-01-18
2019-02-22

Abstract:

As a major etiological agent of human dental caries, resides primarily in biofilms that form on the tooth surfaces, also known as dental plaque. In addition to caries, is responsible for cases of infective endocarditis with a subset of strains being indirectly implicated with the onset of additional extraoral pathologies. During the past 4 decades, functional studies of have focused on understanding the molecular mechanisms the organism employs to form robust biofilms on tooth surfaces, to rapidly metabolize a wide variety of carbohydrates obtained from the host diet, and to survive numerous (and frequent) environmental challenges encountered in oral biofilms. In these areas of research, has served as a model organism for ground-breaking new discoveries that have, at times, challenged long-standing dogmas based on bacterial paradigms such as and . In addition to sections dedicated to carbohydrate metabolism, biofilm formation, and stress responses, this article discusses newer developments in biology research, namely, how interspecies and cross-kingdom interactions dictate the development and pathogenic potential of oral biofilms and how next-generation sequencing technologies have led to a much better understanding of the physiology and diversity of as a species.

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Image of FIGURE 1
FIGURE 1

Carbohydrate metabolism in . While can metabolize a large variety of carbohydrates, the figure shows the metabolism of most common dietary sugars (fructose, glucose, and sucrose). Sucrose is a β2,1-linked disaccharide composed of glucose and fructose that has proven to be the most cariogenic of all carbohydrates. In the extracellular environment, sucrose is a substrate of glucosyltransferase (GTF) and fructosyltransferase (FTF) enzymes, which catalyze the production of glucans and fructans, respectively. The formation of glucans plays a key role in virulence, because they contribute to biofilm buildup by forming a glue-like polysaccharide matrix. Fructans serve as short-term extracellular carbohydrate sources and are degraded by the fructanase enzyme FruA, yielding fructose, which can be internalized for energy production. Glucans are susceptible to the action of an extracellular dextranase, DexA, which breaks down the α1,6-linkages, thereby yielding oligosaccharides (e.g., maltodextrans). After being transported into the cell, oligosaccharides are degraded into monosaccharides by the action of the DexB glucosidase. Oligosaccharides are primarily transported into the cells by ATP-binding cassette (ABC) transporters (e.g., Msm and MalXFGK transport systems), whereas monosaccharides (e.g., glucose and fructose) and disaccharides (e.g., sucrose) are predominantly taken up by the phosphoenolpyruvate:sugar PTS. In , multiple PTSs can transport the same carbohydrate, with at least three PTSs being involved in fructose transport and several PTSs and permeases being involved in glucose transport. In the intracellular environment, carbohydrates are phosphorylated and processed to fructose-6-phosphate (Fru-6-P) and fermented by glycolysis with production of organic acids, mainly lactic acid. In addition, glucosamine-6-phosphate (GlcN-6-P) is synthesized from Fru-6-P and serves as an initial precursor for cell wall biosynthesis. Cells can synthesize an intracellular polysaccharide (IPS), a polymer of the glycogen-amylopectin type, when carbohydrates are in excess that can be stored as intracellular granules and are used as an energy source reserve during starvation.

Source: microbiolspec January 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0051-2018
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Image of FIGURE 2
FIGURE 2

Biofilm formation and host-pathogen interactions in . Early colonizers (e.g., , , and spp. among others) attach to the tooth enamel via salivary proteins and start to form three-dimensional biofilms under noncariogenic conditions. At pH levels close to neutrality, production of HO by peroxigenic bacteria and other antimicrobial products produced by oral commensals prevents the overgrowth of specific pathogens (e.g., ) on dental biofilms. Glycosyltransferases (GTFs) secreted by adsorb onto the enamel pellicle or bacterial surfaces. In the presence of sucrose, GTFs catabolize sucrose to produce large amounts of insoluble and soluble glucans, which contribute to the buildup of a robust extracellular polysaccharide matrix (EPS), particularly insoluble components. The EPS matrix serves as an architectural scaffold for the biofilm structure, mediating tight adherence to the tooth enamel and bacteria, as glucans provide binding sites for glucan-binding proteins (GBP) and other organisms. Extracellular DNA (eDNA) is another functional constituent of the oral biofilm matrix, forming nanofibers that connect cell to cell and cell to substratum and that contribute to biofilm structural integrity and stability. Continuous intake of sucrose by the host leads to a series of ecological and structural shifts that favor the growth of aciduric and highly acidogenic bacteria, such as . These changes alter the oral biofilm metabolism so that copious amounts of organic acids are produced, contributing to a decrease in environmental pH. Once becomes dominant, the secretion of large amounts of mutacins kills nearby competitors such as peroxigenic streptococci. The constant low-pH milieu surrounding the hydroxyapatite structure of the enamel leads to demineralization and initiates the carious process.

Source: microbiolspec January 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0051-2018
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Image of FIGURE 3
FIGURE 3

Acid stress tolerance mechanisms of . The ability of to catalyze fermentable dietary carbohydrates into organic acids can promptly drop the environmental pH. Exposure to sublethal low pH triggers an acid-adaptive response known as ATR (acid tolerance response), which is a robust transcriptional and physiologic adaptation mechanism for pH homeostasis through alteration of proton permeability, generation of neutralizing molecules, and changes in membrane fatty acid composition. The membrane FF-ATPase (F-ATPase) is transcriptionally induced by low pH and serves as the primary mechanism by which protons are extruded to maintain pH homeostasis. The modifications in membrane composition refer to an increase in the proportion of monounsaturated fatty acids (UFA) over saturated fatty acids (SFA) and in the length of the carbon chains composing the membrane fatty acids. Production of neutralizing molecules, such as ammonia and CO, is also an important way to cope with acid stress. In , the agmatine deiminase system (AgDS) converts agmatine, a decarboxylated derivative of arginine found in dental plaque, to ammonia, CO, putrescine, and ATP. The ammonia generated internally may contribute to cytoplasmic buffering, while the ATP generated can be used to fuel proton extrusion via the F-ATPase. A decrease in environmental pH also triggers activation of malolactic fermentation (MLF), which converts malate to the less acidic lactate and to CO. The CO product can then be used for cytoplasmic neutralization by conversion to bicarbonate (HCO ) via carbonic anhydrase.

Source: microbiolspec January 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0051-2018
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Image of FIGURE 4
FIGURE 4

Quorum-sensing systems involved in the regulation of bacteriocin production and competence in . Cell density, nutrient availability, and other environmental conditions induce the expression of , a gene encoding the competence-stimulating peptide (CSP) precursor. The CSP propeptide is cleaved off inside the cell and exported through a specific ABC transporter encoded by . In the extracellular environment, CSP then undergoes a final postexport processing mediated by the SepM protease. Upon reaching a certain threshold, mature CSP is recognized by the two-component system ComDE, triggering a phosphorylation cascade. Activated (phosphorylated) ComE activates transcription of (i) and , creating a positive feedback loop, (ii) genes involved in mutacin production, and (iii) by a yet-to-be-determined mechanism, , the quorum-sensing pathway directly responsible for competence activation via the alternative sigma factor ComX. Once exported to the extracellular milieu, the prepeptide ComS is processed into the peptide pheromone XIP (- or -nducing eptide). XIP is transported back into the cell via the oligopeptide permease system (Opp) and sensed by the Rgg-type regulator ComR. Activated ComR binds to both and promoters, thereby causing auto-induction of ComRS and activation of late (ComX-regulated) competence genes.

Source: microbiolspec January 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0051-2018
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