Fluoride resistance in<i>Streptococcus mutans</i>: a mini review

Liao, Ying; Brandt, Bernd W.; Li, Jiyao; Crielaard, Wim; Loveren, C. van; Deng, Dongsheng

doi:10.1080/20002297.2017.1344509

Cited by 118 publications

(100 citation statements)

References 69 publications

(146 reference statements)

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“…Fluoride is widely used in toothpastes and mouthwashes and is typically added to municipal drinking water. Fluoride cannot only arrest the demineralization of the tooth enamel, but at high concentrations (13 to 647 mM), it inhibits the growth and metabolism of S. mutans (35,36). Growth of the variants compared to that of the parental strain was moderately impaired with addition of 100 g ml Ϫ1 sodium fluoride ( Fig.…”

Section: Resultsmentioning

confidence: 98%

Spontaneously Arising Streptococcus mutans Variants with Reduced Susceptibility to Chlorhexidine Display Genetic Defects and Diminished Fitness

Kaspar

Godwin

Velsko

et al. 2019

Antimicrob Agents Chemother

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Chlorhexidine (CHX) has been used to control dental caries caused by acid-tolerant bacteria such as Streptococcus mutans since the 1970s. Repeat CHX exposure for other bacterial species results in the development of variants with reduced susceptibility that also become more resistant to other antimicrobials. It has not been tested if such variants arise when streptococci are exposed to CHX. Here, we passaged S. mutans in increasing concentrations of CHX and isolated spontaneously arising reduced susceptibility variants (RSVs) from separate lineages that have MICs that are up to 3-fold greater than the parental strain. The RSVs have increased growth rates at neutral pH and under acidic conditions in the presence of CHX but accumulate less biomass in biofilms. RSVs display higher MICs for daptomycin and clindamycin but increased sensitivity to dental-relevant antimicrobials triclosan and sodium fluoride. Plate-based assays for competition with health-associated oral streptococci revealed decreased bacteriocin production by the RSVs, increased sensitivity to hydrogen peroxide, and diminished competitive fitness in a human-derived ex vivo biofilm consortium. Whole-genome sequencing identified common single nucleotide polymorphisms (SNPs) within a diacylglycerol kinase homolog and a glycolipid synthesis enzyme, which could alter the accumulation of lipoteichoic acids and other envelope constituents, as well as a variety of mutations in other genes. Collectively, these findings confirm that S. mutans and likely other streptococci can develop tolerance to CHX but that increased tolerance comes at a fitness cost, such that CHX-induced variants that spontaneously arise in the human oral cavity may not persist.

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Section: Resultsmentioning

confidence: 98%

Spontaneously Arising Streptococcus mutans Variants with Reduced Susceptibility to Chlorhexidine Display Genetic Defects and Diminished Fitness

Kaspar

Godwin

Velsko

et al. 2019

Antimicrob Agents Chemother

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“…Fluoride is widely used in toothpastes and mouthwashes, and is typically added to municipal drinking water. Fluoride can not only arrest the demineralization of the tooth enamel, but at high concentrations (13 – 647 mM) it inhibits growth and metabolism of S. mutans (23, 24). Growth of the CTV3s compared to UA159 was slightly impaired with addition of 100 μg mL −1 sodium fluoride ( Figure 3C ), but significant growth deficiencies were observed with 300 μg mL −1 sodium fluoride.…”

Section: Resultsmentioning

confidence: 99%

Characterization of Spontaneously Arising Chlorhexidine-Tolerant Variants inStreptococcus mutans

Kaspar

et al. 2019

Preprint

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22Broad spectrum antimicrobials, both in dental products and within the clinic, have been 23 used in the suppression of cariogenic bacteria such as Streptococcus mutans for over 40 years. 24One such antimicrobial is chlorhexidine (CHX), and serves as a standard in dental research 25 against which other antimicrobial therapies are compared against for their efficacy. However, 26 very little is known about the mode of action for CHX against Streptococci and whether 27 tolerance can be developed from repeated exposures. Here, we begin to answer such questions 28 by passaging S. mutans with increasing concentrations of CHX and isolating spontaneously-29 arising tolerant variants (CTVs) from separate lineages. We find that these CTVs display a 30 higher minimal inhibitory concentration (MIC) against CHX than the wild-type strain and have 31 altered virulence properties such as acid tolerance and biofilm formation. We record higher 32 MICs for the variants against both daptomycin and bacitracin, but find increased sensitivity to 33 triclosan and sodium fluoride. Measurements of antagonistic capabilities against other health-34 associated oral streptococci show decreased bacteriocin production compared to wild-type and 35 increased sensitivity to hydrogen peroxide. Finally whole genome sequencing of the CTVs show 36 common single nucleotide polymorphisms (SNPs) within a diacylglycerol kinase homolog and a 37 glycolipid synthesis enzyme, altering LTA accumulation and potentially lipid profile of the cell 38 wall. Together, these findings confirm that streptococci may develop tolerance to antimicrobial 39 agents such as CHX but in the case of S. mutans, increased tolerance may come at a fitness 40 cost for survival within oral biofilms that keeps variants suppressed within the population. 42 INTRODUCTION 43Controlling microbial biofilm infections in humans is challenging in part due to the 44 presence of extracellular polymeric substances (EPS) in which the organisms are embedded, 45 the presence of persister cells and sub-populations of cells with low metabolic activity, and 46 exchange of antimicrobial resistance genes through horizontal gene transfer. In the human oral 47 cavity, accumulation of biofilms on the teeth can lead to destruction of tooth mineral when there 48 is frequent and significant localized acidification by organic acids produced as metabolic end 49 products from fermentable carbohydrates (1). The initiation and progression of dental caries can 50 be controlled to a degree through non-specific mechanical removal of the biofilms or by 51 treatment with various chemical agents that include fluoride, xylitol or chlorhexidine (CHX) (2, 52 3). While the effectiveness of CHX in caries prevention is not definitively established and there 53 can be undesirable side effects (e.g. staining, irritation of host tissues) (4), CHX remains a 54 standard against which antimicrobial therapies are compared for their efficacy in the 55 suppression of caries-causing bacteria, such as Streptococcus mutans (5-7). Currently...

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“…Most patients are unable to achieve sufficient plaque removal by mechanical oral hygiene practices, so the relevance of the chemotherapeutic agents has increased with this perception . Fluoride is the most popular chemotherapeutic agent, and it is widely used in many oral care products, such as toothpastes, mouthwashes and gels . Mouthwashes (MWs) are an ideal vehicle to incorporate in chemotherapeutic agents and are appreciated by the public because of their ease of use.…”

Section: Introductionmentioning

confidence: 99%