Medicinal Chemistry Updates on Bacterial Efflux Pump Modulators

Durães, Fernando; Pinto, Madalena; Sousa, Emı́lia

doi:10.2174/0929867325666180209142612

Cited by 24 publications

(25 citation statements)

References 168 publications

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“…Higher MIC values of chlorhexidine digluconate against Pseudomonas aeruginosa and Staphylococcus aureus strains were decreased by adding efflux pump inhibitors [41]. Efflux pumps belong to five families, regarding antimicrobial resistance the ABC pumps in gram-positive bacteria and the RND pumps in gram-negative bacteria are most important [42]. All used inhibitors on efflux pumps increased the sensitivity of the P. gingivalis J374-1 strain to taurolidine.…”

Section: Discussionmentioning

confidence: 99%

Taurolidine Acts on Bacterial Virulence Factors and Does Not Induce Resistance in Periodontitis-Associated Bacteria—An In-Vitro Study

et al. 2020

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The aims of the present study were: (a) to determine the mechanism of action of taurolidine against bacterial species associated with periodontal disease, and (b) to evaluate the potential development of resistance against taurolidine as compared with minocycline. After visualizing the mode of action of taurolidine by transmission electron micrographs, the interaction with most important virulence factors (lipopolysaccharide (LPS), Porphyromonas gingivalis gingipains, Aggregatibacter actinomycetemcomitans leukotoxin), was analyzed. Then, 14 clinical isolates from subgingival biofilm samples were transferred on agar plates containing subinhibitory concentrations of taurolidine or minocycline up to 50 passages. Before and after each 10 passages, minimal inhibitory concentrations (MICs) were determined. Increasing MICs were screened for efflux mechanism. Taurolidine inhibited in a concentration-dependent manner the activities of LPS and of the arginine-specific gingipains; however, an effect on A. actinomycetemcomitans leukotoxin was not detected. One P. gingivalis strain developed a resistance against taurolidine, which was probably linked with efflux mechanisms. An increase of MIC values of minocycline occurred in five of the 14 included strains after exposure to subinhibitory concentrations of the antibiotic. The present results indicate that: (a) taurolidine interacts with LPS and gingipains, and (b) development of resistance seems to be a rare event when using taurolidine.

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Section: Discussionmentioning

confidence: 99%

Taurolidine Acts on Bacterial Virulence Factors and Does Not Induce Resistance in Periodontitis-Associated Bacteria—An In-Vitro Study

et al. 2020

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“…Higher MIC values of chlorhexidine digluconate against Pseudomonas aeruginosa and Staphylococcus aureus strains were decreased by adding efflux pump inhibitors [47]. Efflux pumps belong to five families, regarding antimicrobial resistance the ABC pumps in gram-positive bacteria and the RND pumps in gram-negative bacteria are most important [48]. All used inhibitors on efflux pumps increased the sensitivity of the P. gingivalis J374-1 strain to taurolidine.…”

Section: Discussionmentioning

confidence: 99%

Taurolidine acts on bacterial virulence factors and does not induce resistance in periodontitis-associated bacteria

Radakovic

Schmid

Andreoli

et al. 2019

Preprint

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Background Taurolidine is thought to be an alternative antimicrobial in periodontal therapy. The purpose of this follow-up taurolidine study was to determine in more detail the mode of action of taurolidine against bacterial species being associated with periodontal disease. Further, a potential development of resistance against taurolidine in comparison with minocycline was to evaluate. Results Visualizing the mode of action of taurolidine to Porphyromonas gingivalis by scanning and transmission electron micrographs showed in part pores and release of constituents from the cell wall. The interaction of taurolidin with bacterial cell wall is also supported by the finding that taurolidine inhibited in a concentration-dependent manner the activities of LPS and of the P. gingivalis arginine-specific gingipains. However, an effect on A. actinomycetemcomitans leukotoxin was not found. When transferring 14 clinical isolates from subgingival biofilm samples (4 P. gingivalis, 2 A. actinomycetemcomitans, 2 Tannerella forsythia, 2 Fusobacterium nucleatum, 4 oral streptococci) on agar plates containing subinhibitory concentrations of taurolidine up to 50 passages, one P. gingivalis strain developed a resistance against taurolidine which was probably linked with efflux mechanisms. When antimicrobial pressure was removed, MIC reverted to baseline value. Testing development of resistance to minocycline in a similar way, an increase of MIC values occurred in five of the 14 included strains after exposure to subinhibitory concentrations of the antibiotic. Efflux might play a role in one A. actinomycetemcomitans strains, but obviously not in the other four strains. Removing antimicrobial pressure for a few passages did not revert the increased MIC values. Conclusion Taurolidine interacts with LPS and gingipains. Development of resistance seems to be a rare event when applying taurolidine. A potential development of resistance might be associated with efflux mechanisms.

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“…In addition to overexpression of β-lactamases in bacteria, another known resistance mechanism is related to efflux pumps, thus the discovery and design of novel antibacterial drugs that could act by inhibiting the action of these pumps is an exciting approach [ 67 , 68 ]. It has been recognized that boronic acid derivatives can be promising inhibitors of chromosomal NorA efflux pump of Staphylococcus aureus .…”

Section: Synthesis and Biological Applications Of Boronic Acids Dementioning

confidence: 99%

Boronic Acids and Their Derivatives in Medicinal Chemistry: Synthesis and Biological Applications

et al. 2020

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Boron containing compounds have not been widely studied in Medicinal Chemistry, mainly due to the idea that this group could confer some toxicity. Nowadays, this concept has been demystified and, especially after the discovery of the drug bortezomib, the interest for these compounds, mainly boronic acids, has been growing. In this review, several activities of boronic acids, such as anticancer, antibacterial, antiviral activity, and even their application as sensors and delivery systems are addressed. The synthetic processes used to obtain these active compounds are also referred. Noteworthy, the molecular modification by the introduction of boronic acid group to bioactive molecules has shown to modify selectivity, physicochemical, and pharmacokinetic characteristics, with the improvement of the already existing activities. Besides, the preparation of compounds with this chemical group is relatively simple and well known. Taking into consideration these findings, this review reinforces the relevance of extending the studies with boronic acids in Medicinal Chemistry, in order to obtain new promising drugs shortly.

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Medicinal Chemistry Updates on Bacterial Efflux Pump Modulators

Cited by 24 publications

References 168 publications

Taurolidine Acts on Bacterial Virulence Factors and Does Not Induce Resistance in Periodontitis-Associated Bacteria—An In-Vitro Study

Taurolidine Acts on Bacterial Virulence Factors and Does Not Induce Resistance in Periodontitis-Associated Bacteria—An In-Vitro Study

Taurolidine acts on bacterial virulence factors and does not induce resistance in periodontitis-associated bacteria

Boronic Acids and Their Derivatives in Medicinal Chemistry: Synthesis and Biological Applications

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