Effects of Antibiotics on Quorum Sensing in
            <i>Pseudomonas aeruginosa</i>

Skindersoe, Mette E.; Alhede, Morten; Phipps, Richard Kerry; Yang, Liang; Jensen, Peter Østrup; Rasmussen, Trine Bernholdt; Bjarnsholt, Thomas; Tolker‐Nielsen, Tim; Høiby, Niels; Givskov, Michael

doi:10.1128/aac.01230-07

Cited by 321 publications

(289 citation statements)

References 97 publications

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“…Previous studies have provided evidence that antimicrobial agents at subinhibitory concentrations may induce alternations in bacterial properties, including changes in morphology and ultrastructure [53], as well as inhibition or stimulation of virulence factors [54–56]. In our study, 1/4 MIC and 1/8 MIC of GH12 could slightly enhance acid production, and cause different changes in acid tolerance and EPS production (Figures 2–4).…”

Section: Discussionsupporting

confidence: 49%

Antimicrobial peptide GH12 suppresses cariogenic virulence factors of Streptococcus mutans

Wang

Jiang

et al. 2018

Journal of Oral Microbiology

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Cariogenic virulence factors of Streptococcus mutans include acidogenicity, aciduricity, and extracellular polysaccharides (EPS) synthesis. The de novo designed antimicrobial peptide GH12 has shown bactericidal effects on S. mutans, but its interaction with virulence and regulatory systems of S. mutans remains to be elucidated. The objectives were to investigate the effects of GH12 on virulence factors of S. mutans, and further explore the function mechanisms at enzymatic and transcriptional levels. To avoid decrease in bacterial viability, we limited GH12 to subinhibitory levels. We evaluated effects of GH12 on acidogenicity of S. mutans by pH drop, lactic acid measurement and lactate dehydrogenase (LDH) assay, on aciduricity through survival rate at pH 5.0 and F1F0-ATPase assay, and on EPS synthesis using quantitative measurement, morphology observation, vertical distribution analyses and biomass calculation. Afterwards, we conducted quantitative real-time PCR to acquire the expression profile of related genes. GH12 at 1/2 MIC (4 mg/L) inhibited acid production, survival rate, EPS synthesis, and biofilm formation. The enzymatic activity of LDH and F1F0-ATPase was inhibited, and ldh, gtfBCD, vicR, liaR, and comDE genes were significantly downregulated. In conclusion, GH12 inhibited virulence factors of S. mutans, through reducing the activity of related enzymes, downregulating virulence genes, and inactivating specific regulatory systems.

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Section: Discussionsupporting

confidence: 49%

Antimicrobial peptide GH12 suppresses cariogenic virulence factors of Streptococcus mutans

Wang

Jiang

et al. 2018

Journal of Oral Microbiology

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“…These reductions coincided with reduced Las-and Rhl-dependent gene transcription and have been corroborated by microarray and proteomic studies (319,320), which found, in addition to QS gene misregulation, a reduction in levels of oxidative stress and motility-related genes but an increase in type III secretion (TTS)-related genes. The diminished response to oxidative stress conditions may account for the reduced cell viability in late stationary phase that was reported to occur with increasing concentrations of macrolides (318,319).…”

Section: Antibiotics As Qs Inhibitorsmentioning

confidence: 71%

“…In a screen of 11 antimicrobial compounds, a cephalosporin (ceftazidime [CFT]) and a fluoroquinolone (ciprofloxacin [CPR]) were also able to inhibit AHL production in P. aeruginosa and showed regulatory effects very similar to that seen for AZM, as determined by transcriptional profiling after treatment with each antibiotic (320). As the structural compositions of AZM, CFT, and CPR are highly divergent, it appears unlikely that each directly blocks activity of AHL synthase proteins and instead seems more probable that a separate, unifying theme for inhibition is at work.…”

Section: Antibiotics As Qs Inhibitorsmentioning

confidence: 99%

“…As the structural compositions of AZM, CFT, and CPR are highly divergent, it appears unlikely that each directly blocks activity of AHL synthase proteins and instead seems more probable that a separate, unifying theme for inhibition is at work. It has been suggested that cellular responses to the drugs lead to decreased membrane permeability to block antibiotic penetration, and consequentially this also inhibits autoinducer transfer (320). Until this is tested directly, other mechanisms should be considered, including effects on general stress responses and resistance to reactive oxygen species.…”

Section: Antibiotics As Qs Inhibitorsmentioning

confidence: 99%

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Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

677

556

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SUMMARY Cell-cell communication, or quorum sensing, is a widespread phenomenon in bacteria that is used to coordinate gene expression among local populations. Its use by bacterial pathogens to regulate genes that promote invasion, defense, and spread has been particularly well documented. With the ongoing emergence of antibiotic-resistant pathogens, there is a current need for development of alternative therapeutic strategies. An antivirulence approach by which quorum sensing is impeded has caught on as a viable means to manipulate bacterial processes, especially pathogenic traits that are harmful to human and animal health and agricultural productivity. The identification and development of chemical compounds and enzymes that facilitate quorum-sensing inhibition (QSI) by targeting signaling molecules, signal biogenesis, or signal detection are reviewed here. Overall, the evidence suggests that QSI therapy may be efficacious against some, but not necessarily all, bacterial pathogens, and several failures and ongoing concerns that may steer future studies in productive directions are discussed. Nevertheless, various QSI successes have rightfully perpetuated excitement surrounding new potential therapies, and this review highlights promising QSI leads in disrupting pathogenesis in both plants and animals.

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“…If such QSIs are free of toxic side effects, they may be used to treat biofilm infections like chronic P. aeruginosa lung infections [71]. Interestingly, some antibiotics, like ceftazidime and ciprofloxacin and the macrolides azithromycin and clarithromycin [72], inhibit QS in P. aeruginosa at sub-MIC concentrations leading to inhibition of the virulence of these bacteria. However, azithromycin and clarithromycin, in contrast with ciprofloxacin and ceftazidime, cannot inhibit bacterial growth at obtainable concentrations in vivo.…”

Section: Quorum Sensing Inhibitors (Qsi)mentioning

confidence: 99%

The clinical impact of bacterial biofilms

Høiby¹,

Ciofu²,

Johansen³

et al. 2011

Int J Oral Sci

Self Cite

721

536

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Bacteria survive in nature by forming biofilms on surfaces and probably most, if not all, bacteria (and fungi) are capable of forming biofilms. A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and extracellular DNA. Bacterial biofilms are resistant to antibiotics, disinfectant chemicals and to phagocytosis and other components of the innate and adaptive inflammatory defense system of the body. It is known, for example, that persistence of staphylococcal infections related to foreign bodies is due to biofilm formation. Likewise, chronic Pseudomonas aeruginosa lung infections in cystic fibrosis patients are caused by biofilm growing mucoid strains. Gradients of nutrients and oxygen exist from the top to the bottom of biofilms and the bacterial cells located in nutrient poor areas have decreased metabolic activity and increased doubling times. These more or less dormant cells are therefore responsible for some of the tolerance to antibiotics. Biofilm growth is associated with an increased level of mutations. Bacteria in biofilms communicate by means of molecules, which activates certain genes responsible for production of virulence factors and, to some extent, biofilm structure. This phenomenon is called quorum sensing and depends upon the concentration of the quorum sensing molecules in a certain niche, which depends on the number of the bacteria. Biofilms can be prevented by antibiotic prophylaxis or early aggressive antibiotic therapy and they can be treated by chronic suppressive antibiotic therapy. Promising strategies may include the use of compounds which can dissolve the biofilm matrix and quorum sensing inhibitors, which increases biofilm susceptibility to antibiotics and phagocytosis.

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Effects of Antibiotics on Quorum Sensing in Pseudomonas aeruginosa

Cited by 321 publications

References 97 publications

Antimicrobial peptide GH12 suppresses cariogenic virulence factors of Streptococcus mutans

Antimicrobial peptide GH12 suppresses cariogenic virulence factors of Streptococcus mutans

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

The clinical impact of bacterial biofilms

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