In vitro development of chlorhexidine resistance in Streptococcus sanguis and its transmissibility by genetic transformation

Westergren, Gudrun; Emilson, Claes‐Göran

doi:10.1111/j.1600-0722.1980.tb01220.x

Cited by 24 publications

(21 citation statements)

References 28 publications

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“…1). Little is known about adaptation to CHX, although it has been shown that strains of S. sanguis can develop resistance in vivo (Emilson and Fornell, 1976) and when grown in increasing concentrations of CHX in vitro (Westergren and Emilson, 1980). The data from our pH-fall studies also suggest that the community had become more resistant to CHX after pulsing (Table 3), although this was not substantiated by measurements of the inhibition of glycolytic rates (Fig.…”

Section: Discussionmentioning

confidence: 54%

A Mixed-culture Chemostat System to Predict the Effect of Anti-microbial Agents on the Oral Flora: Preliminary Studies using Chlorhexidine

McDermid¹,

McKee²,

Marsh³

1987

J Dent Res

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A mixed-culture chemostat system, composed of nine bacterial species representative of plaque in health and disease, has been assessed as an improved laboratory method of evaluating the likely in vivo effects of antimicrobial agents used in dentistry. The advantages of the system include reproducibility, the long-term stable cultivation of bacteria under controllable conditions, and repeated sampling, for bacteriological and biochemical studies, without disrupting the stability of the community. The effects of (i) the continuous provision of chlorhexidine (CHX) and (ii) three pulses of CHX (final concentration in both experiments = 0.24 mmol/L) on the composition of the chemostat communities were monitored. Only L. casei survived the continuous provision of CHX; the other bacteria were killed and were lost at different rates which generally corresponded to their known sensitivities to CHX. After each CHX pulse, the numbers of bacteria fell markedly. Again, L. casei was least affected, while A. viscosus, B. intermedius, and F. nucleatum were temporarily undetectable but returned to their original levels within 2-4 generation times. Counts of S. mutans were affected more by CHX than those of S. sanguis or S. mitior. The effect of successive pulses of CHX on the viability of some bacteria and on acid production (as measured by pH-fall experiments) decreased, suggesting that adaptation to CHX had occurred. The fact that the in vitro observations paralleled previous clinical findings suggests that the mixed-culture system could be used as a predictive model of the probable effect on the oral flora of new anti-microbial agents prior to expensive trials in animals or human volunteers.

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Section: Discussionmentioning

confidence: 54%

A Mixed-culture Chemostat System to Predict the Effect of Anti-microbial Agents on the Oral Flora: Preliminary Studies using Chlorhexidine

McDermid¹,

McKee²,

Marsh³

1987

J Dent Res

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“…Their concentrations, however, were low compared with those in the present study (0.07-0.15 mM CHX and 4-8 mM F vs. 1.98 mM CHX and 53 mM F, re spectively), and hardly any effect on viability was ob served after treatment with the solutions of the low concentrations. Apparently, the less concentrated so lutions applied in the clinical situation, the less side effects are to be awaited [Meurman, 1986], Another problem, however, may arise if S. mutans strains also develop resistance to CHX as has been shown to l e the case with Streptococcus sanguis strains [Wester gren and Emilson, 1980], In the present series the S. mutans cells did not show any increased staining in the electron micro graphs after CHX treatment when compared with the controls (see figures 1-4). We have earlier observed a distinct increase in electron density at cell walls oi bacteria in subgingival plaque samples treated with 2% CHX when compared with those treated with sa line [Meurman and Asikainen, unpubl.].…”

Section: Discussionmentioning

confidence: 99%

Ultrastructure, Growth, and Adherence of Streptococcus mutans after Treatment with Chlorhexidine and Fluoride

Jh¹

1988

Caries Res

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Ultrastructure, growth, and adherence to hydroxyapatite of Streptococcus mutans ATCC 27351 was studied after treating bacterial suspensions for 1 h with 0.1 % chlorhexidine gluconate (CHX), 0.1 % sodium fluoride (F), or a combination of these two (CHX + F). Cells treated with 0.1 M phosphate-buffered saline were used as controls. Electron microscopy revealed that the treatment with CHX or CHX + F caused disruption of streptococcal cells with vacuolization and sloughing and leakage of cytoplasmic constituents. The F-treated specimens appeared the same as the controls, where the ultrastructure was mostly normal. In the adherence assay, radiolabelled bacteria attached themselves in 77.9% to hydroxyapatite in the control series. Treatment with F reduced the adsorption to 63.7%, and treatment with CHX and CHX + F to 57.4 and 43.4%, respectively. The reduction in CHX and CHX + F series when compared with the controls was statistically highly significant. The synergistic effect of CHX and F was further verified in minimum inhibitory concentration titrations where total inhibition was observed at 0.5% F and 0.1% CHX, respectively, while CHX + F inhibited growth at 0.05%. Thus, F does not interfere with the toxic effect of CHX on S.mutans cells, but, on the contrary, the two chemicals seem to exert a synergistic mode of action.

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“…One agent which has been shown to inhibit the formation of dental plaque in both short-term and longterm clinical studies is chlorhexidine (Gjermo and Eriksen, 1974;Joyston-Bechal et al, 1979;Loe and Rindom Schi0tt, 1970). Development of bacterial resistance to chlorhexidine is rare (Davies et al, 1954;Hennessey, 1973;Rindom Schi0tt et al, 1976;Westergren and Emilson, 1980). This is perhaps because chlorhexidine does not act on specific protein receptors or enzymes as do many antibiotics, but rather exerts its inhibitory effect by a generalized perturbation of the bacterial membrane Longworth, 1964, 1965).…”

mentioning

confidence: 92%

Structural Determinants of Activity of Chlorhexidine and Alkyl Bisbiguanides Against the Human Oral Flora

Baker¹,

Coburn

Genco³

et al. 1987

J Dent Res

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We assayed chlorhexidine and a series of its analogues, in which the chlorophenyl terminal substituents were replaced with alkyl chains, for their in vitro antimicrobial activity against the Gram-negative and Gram-positive oral bacteria. Changes in antimicrobial activity were correlated with changes in agent structure for identification of structural criteria which may be important in the optimization of agent activity. Chlorhexidine showed substantial antimicrobial activity against the Gram-negative as well as the Gram-positive oral bacteria. The alkyl agents were comparable with chlorhexidine in their activity against Bacteroides gingivalis and Bacteroides intermedius, black-pigmented Gram-negative obligate anaerobes associated with periodontal disease in adults. Alkyl agents alexidine, heptihexidine (1,6-bis-n-heptylbiguanidohexane), hexoctidine (1,8-bis-n-hexylbiguanidoctane), and hexhexidine (1,6-bis-n-hexylbiguanidohexane), as well as chlorhexidine, were active against Actinobacillus actinomycetemcomitans, a Gram-negative organism associated with localized juvenile periodontitis. Hexidecidine (1,10-bis-n-hexylbiguanidodecane) and heptoctidine (1,8-bis-n-heptylbiguanidooctane) were more active, and hexhexidine was as active as chlorhexidine against Fusobacterium nucleatum, also associated with periodontal disease. Seven of the agents were more active than chlorhexidine against Actinomyces species. All test agents were active against Streptococcus mutans, a Gram-positive coccus associated with dental caries. Hexidecidine had activity equal to that of chlorhexidine when evaluated against the entire battery of organisms. Analysis of structure-activity relationships revealed that alkyl chains could replace chlorophenyl groups with retention or improvement of antimicrobial activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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In vitro development of chlorhexidine resistance in Streptococcus sanguis and its transmissibility by genetic transformation

Cited by 24 publications

References 28 publications

A Mixed-culture Chemostat System to Predict the Effect of Anti-microbial Agents on the Oral Flora: Preliminary Studies using Chlorhexidine

A Mixed-culture Chemostat System to Predict the Effect of Anti-microbial Agents on the Oral Flora: Preliminary Studies using Chlorhexidine

Ultrastructure, Growth, and Adherence of Streptococcus mutans after Treatment with Chlorhexidine and Fluoride

Structural Determinants of Activity of Chlorhexidine and Alkyl Bisbiguanides Against the Human Oral Flora

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