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Natural Preservatives
Published in Philip A. Geis, Cosmetic Microbiology, 2020
Lactoperoxidase belongs to the peroxidase family of enzymes and has been established as a key component of a broader system in nature which yields natural antibacterial components as part of the body’s defense. The lactoperoxidase effect was first observed in milk. In situ, the mechanism involves the reaction of lactoperoxidase with hydrogen peroxide (from the presence of existing bacteria) and electron donors like the thiocyanate ion to produce a cascade of antimicrobial metabolites (e.g., hypothiocyanate). Commercially available systems typically use a second component system. The first component consists of the enzymes lactoperoxidase and glucose oxidase. The second component contains the substrates glucose, thiocyanate, and iodide. In combination with oxygen, a reaction is catalyzed, yielding the antimicrobial metabolites hypoiodite and hypothiocyanite (Figure 3.6).
Oral Biofilms and Their Implication in Oral Diseases
Published in Chaminda Jayampath Seneviratne, Microbial Biofilms, 2017
Georgios N. Belibasakis, Nagihan Bostanci
The demineralisation of the enamel and dentin occurring in dental caries is a consequence of a local drop in pH, caused by bacteria of the biofilm. Evidently, supragingival biofilms are directly exposed to the openness of the oral cavity and the affluent sugar availability in our nutrition. Given the appropriate fermentable carbohydrates, overgrowth and maturation of a supragingival biofilm will result in the domination of aerobic, or aerotolarant, and saccharolytic lactic acid–producing bacteria. As such, acidogenic and aciduric members of the mutans streptococci and lactobacilli are most well adapted to grow under these conditions, and their presence correlates well with caries. These bacteria adhere by means of cell surface adhesins to the receptors which are present on the saliva-coated tooth [6]. They degrade the carbohydrates derived from foods and form organic acids such as lactic, formic, acetic and/or succinic acid. Subsequently, the supragingival plaque pH falls to around 4 in several minutes. In particular, Streptococcus mutans is the dominating cariogenic species, followed by Streptococcus sobrinus and various members of the Lactobacillus spp. [7]. On the other hand, an inverse relationship between dental caries and other members of the Streptococcus spp. has also been reported, in particular Streptococcus sanguinis. S. sanguinis is capable of oxidising thiocyanate (SCN-) in saliva to hypothiocyanite (OSCN-), thereby repressing the glycolytic activity of mutans [8]. A number of Actinomyces spp. have been associated with the root cementum caries. This is a form of the disease that occurs in periodontitis-affected teeth, in which the root surface is exposed due to gingival recession. It is also proposed that the hard-tissue specificity (e.g. enamel, dentin or cementum) may influence the establishment of a caries-specific biofilm microflora [9,10].
Factors Controlling the Microflora of the Healthy Mouth
Published in Michael J. Hill, Philip D. Marsh, Human Microbial Ecology, 2020
The oral mucosa is protected by glycoproteins (mucins) forming a viscous layer suitable for trapping microorganisms and antigens, which are then removed by the continuous renewal of the slime layer and by desquamation of the epithelial cells. Furthermore, antimicrobial proteins may be concentrated on the mucosal surfaces by binding to the mucin. The acquired pellicle on the teeth also has protective functions, mainly against the demineralizing effects of dietary acids. The pellicle is, however, colonized by plaque-forming bacteria, although it does offer some resistance compared with hydroxyapatite without a saliva coating, perhaps in part due to its content of antimicrobial factors such as lysozyme and immunoglobulin A.129,176 Salivary glycoproteins also serve to eliminate bacteria from the mouth by aggregating them or covering their adhesins so that they are swallowed.135,175,177 Lysozyme is a small cationic protein present in saliva and other secretions as well as in the granules of phagocytic cells. It is bactericidal for some bacteria by the hydrolysis of cell wall peptidoglycan. Most oral bacteria are aggregated rather than lysed by lysozyme binding to them. S. mutans is, however, lysed by the combined effect of lysozyme and inorganic anions or protease, possibly through activation of autolytic enzymes.178 Salivary histidine-rich polypeptides also have bactericidal and fungicidal effect.178 Lactoferrin is an iron-binding glycoprotein which could inhibit bacterial growth through iron depletion. In addition, a bactericidal effect on S. mutans has been demonstrated.179 Salivary peroxidase is an enzyme with a hemin prosthetic group. Similar enzymes are present in milk (lactoperoxidase) and in neutrophils (myeloperoxidase). Peroxidase is part of a bacteriostatic system involving oxidation of salivary thiocyanate to hypothiocyanite by hydrogen peroxide produced by some oral bacteria. In this way toxic hydrogen peroxide is removed from the mouth. In addition, hypothiocyanite has a bacteriostatic effect because it inhibits sugar transport and glycolysis in bacteria by oxidation of sulfhydryl groups in some enzymes. The effect is, however, reversible when hydrogen peroxide production stops in the inhibited bacteria.180 The antimicrobial effect of peroxidasethiocyanate can be enhanced and acid production in dental plaque reduced by application of a hydrogen peroxide-generating enzyme system as a mouthwash,181 and a toothpaste containing such a system is commercially available.
Gram negative infections in cystic fibrosis: a review of preventative and treatment options
Published in Expert Opinion on Orphan Drugs, 2020
Charlotte Addy, Steven Caskey, Damian Downey
Nitric Oxide (NO) is an anti-inflammatory compound, with some anti-bacterial properties. A randomized, placebo-controlled phase 2 trial of inhaled NO is underway in the US. It investigates the effect of NO on lung function, and bacterial density in adults with CF chronically colonized with S. aureus, Pa, and S. maltophilia (NCT02498535). NO also has anti-biofilm properties which could impact bacterial growth, and are under investigation (PMID 28,750,737). Hypothiocyanite and lactoferrin are molecules involved in inflammatory signaling and host bacterial defense mechanisms. Levels of these molecules are low in the airway surface liquid of PWCF, contributing to the development of chronic bacterial growth in the CF lung. A phase 1 study of an inhalational compound (ALX-009), combining these two molecules, is exploring the effect on chronic bacterial growth in healthy volunteers, PWCF and people with non-CF bronchiectasis (NCT02598999). Chronic bacterial growth in the CF lung is facilitated by biofilms generated by bacteria. An inhaled dry powder, Alginate Oligosaccharide (OligoG), derived from seaweed, has been shown to improve mucus clearability and disrupt biofilm formation. One European Phase IIb study is complete (NCT02157922), with full results awaited, and a second phase IIB study is currently recruiting in Australia (NCT03822455). An inhaled glycopolymer (SNSP113) has been designed to disturb and disrupt biofilm formation. With evidence of safety in a phase 1a healthy volunteer study, a phase 1B study in PWCF is planned (NCT03309358).
Integrated hypothesis of dental caries and periodontal diseases
Published in Journal of Oral Microbiology, 2020
Bente Nyvad, Nobuhiro Takahashi
A classic, but complicated example of a host-derived metabolic pathway is the salivary peroxidase-hypothiocyanate system. Hypothiocyanate is secreted from saliva and reacts with bacteria-derived hydrogen peroxide in reactions involving salivary peroxidases. Hypothiocyanate is finally converted to hypothiocyanite, which inhibits several bacterial glycolytic enzymes, potentially leading to reduced bacterial acid production [67]. Lastly, some facultative bacteria, such as non-mutans streptococci can produce hydrogen peroxide via catalysis of NADH oxidase and pyruvate oxidase [68]. Hydrogen peroxide is cytotoxic and acts as a strong oxidizer in both the host and in bacteria, but some oral bacteria possess catalases and peroxidases, while host tissues possess catalases, which are used to remove hydrogen peroxide. However, the relative role of these oxidative activities in maintaining dynamic stability of the microbiota needs further clarification.