Quorum Sensing and Quorum Quenching with a Focus on Cariogenic and Periodontopathic Oral Biofilms

Wright, Patricia P.; Ramachandra, Srinivas Sulugodu

doi:10.3390/microorganisms10091783

Cited by 29 publications

(22 citation statements)

References 131 publications

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“…S. mutans has several two- and three-component QS systems in which post-translationally modified oligopeptides are used as autoinducers [ 1 , 17 , 59 ]. One of these autoinducers is the 21-competence stimulating peptide (21-CSP) produced as a precursor by the comC gene, that during the export through the ABC ComAB transporter is cleaved into the mature 21-CSP [ 1 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…21-CSP can be further cleaved into 18-CSP by SepM [ 19 , 60 ] ( Figure 11 ). The mature CSPs bind to the membrane ComD receptor leading to the induction of a phosphorelay with consequent phosphorylation and activation of the transcriptional regulator ComE [ 17 ]. Another family of autoinducers is the autoinducer-2 (AI-2) whose production relies on the luxS gene [ 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is composed of the comAB and the comCDE operons. The comC gene encodes a precursor of CSP, while comD is transcribed into a histidine kinase (HK) sensor protein, and comE encodes for a cognate response regulator [ 14 , 15 , 16 , 17 ]. The CSP propeptide is transported out of the bacteria through the integrated ComAB ABC transporter, and during this transmembrane transport it is processed into 21-CSP.…”

Section: Introductionmentioning

confidence: 99%

“…The luxS gene encodes for an enzyme involved in the production of (S)-4,5-dihydroxy-2,3-pentandione (DPD), which is a precursor of AI-2 furanones. When the extracellular AI-2 level exceeds a threshold, it induces a signal cascade that leads to large alterations in gene expression, among others, the induction of virulence genes [ 17 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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The Antibacterial Effect of Cannabigerol toward Streptococcus mutans Is Influenced by the Autoinducers 21-CSP and AI-2

et al. 2023

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Bacteria can communicate through an intercellular signaling system referred to as quorum sensing (QS). The QS system involves the production of autoinducers that interact with their respective receptors, leading to the induction of specific signal transduction pathways. The QS systems of the oral cariogenic Streptococcus mutans regulate the maturation of biofilms and affect its virulent properties. We have previously shown that the non-psychoactive compound cannabigerol (CBG) of the Cannabis sativa L. plant has anti-bacterial and anti-biofilm activities towards S. mutans. Here we were interested in investigating the effect of the two QS systems ComCDE and LuxS on the susceptibility of S. mutans to CBG and the anti-QS activities of CBG. This was assessed by using various comCDE and luxS mutant strains and complementation with the respective autoinducers, competence stimulating peptide (CSP) and (S)-4,5-dihydroxy-2,3-pentandione (DPD, pre-AI-2). We found that S. mutans comCDE knockout strains were more sensitive to the anti-bacterial actions of CBG compared to the WT strain. Exogenously added 21-CSP prevented the anti-bacterial actions caused by CBG on the ΔcomC, ΔcomE and ΔluxS mutants, while having no effect on the susceptibility of the WT and ΔcomCDE strains to CBG. Exogenously added DPD increased the susceptibility of WT and ΔluxS to CBG. Vice versa, CBG significantly reduced the 21-CSP-induced expression of comCDE genes and ComE-regulated genes and suppressed the expression of luxS with concomitant reduction in AI-2 production. DPD induced the expression of comCDE genes and ComE-regulated genes, and this induction was repressed by CBG. 21-CSP alone had no significant effect on luxS gene expression, while ΔcomCDE strains showed reduced AI-2 production. In conclusion, our study shows that the susceptibility of S. mutans to CBG is affected by the ComCDE and LuxS QS pathways, and CBG is a potential anti-QS compound for S. mutans. Additionally, we provide evidence for crosstalk between the ComCDE and LuxS QS systems.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Antibacterial Effect of Cannabigerol toward Streptococcus mutans Is Influenced by the Autoinducers 21-CSP and AI-2

et al. 2023

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“…39 The presence of extracellular polymer substance acting as a physical barrier, slow bacterial growth rate, bacterial cell mutability, and quorum sensing are various elements involved in the development of antimicrobial resistance. 44,47 In the current study, cultures were maintained in the CDC reactor for 4.5 days. As such, our observation of live bacteria within inner layers and apparent resistance to amoxicillin treatment at later timepoints is likely reflecting the action of such mechanisms occurring in the mature biofilms.…”

Section: Discussionmentioning

confidence: 99%

An in vitro dynamic bioreactor model for evaluating antimicrobial effectiveness on periodontal polymicrobial biofilms: a proof‐of‐concept study

Ramachandra,

Sime,

Naicker

et al. 2023

Journal of Periodontology

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BackgroundThe aim of this study was to investigate an in vitro dynamic bioreactor model by evaluating the antimicrobial effect of clinically relevant amoxicillin doses on polymicrobial microcosm biofilms derived from subgingival plaque.MethodsBiofilms from pooled subgingival plaque were grown for 108 hours in control and experimental dynamic biofilm reactors. Amoxicillin was subsequently infused into the experimental reactor to simulate the pharmacokinetic profile of a standard 500 mg thrice‐daily dosing regimen over 5 days and biofilms were assessed by live/dead staining, scanning electron microscopy, and quantitative polymerase chain reaction.ResultsFollowing establishment of the oral microcosm biofilms, confocal imaging analysis showed a significant increase in dead bacteria at 8 hours (p = 0.0095), 48 hours (p = 0.0070), 96 hours (p = 0.0140), and 120 hours (p < 0.0001) in the amoxicillin‐treated biofilms compared to the control biofilms. Nevertheless, viable bacteria remained in the center of the biofilm at all timepoints. Significant reductions/elimination in Campylobacter rectus, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Peptostreptococcus anaerobius was observed among the amoxicillin‐treated biofilms at the 96 and 120 hour timepoints.ConclusionA novel in vitro dynamic model of oral microcosm biofilms was effective in modeling the antimicrobial effect of a pharmacokinetically simulated clinically relevant dose of amoxicillin.

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Evaluating models and assessment techniques for understanding oral biofilm complexity

Ramachandra,

Wright,

Han

et al. 2023

MicrobiologyOpen

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Oral biofilms are three‐dimensional (3D) complex entities initiating dental diseases and have been evaluated extensively in the scientific literature using several biofilm models and assessment techniques. The list of biofilm models and assessment techniques may overwhelm a novice biofilm researcher. This narrative review aims to summarize the existing literature on biofilm models and assessment techniques, providing additional information on selecting an appropriate model and corresponding assessment techniques, which may be useful as a guide to the beginner biofilm investigator and as a refresher to experienced researchers. The review addresses previously established 2D models, outlining their advantages and limitations based on the growth environment, availability of nutrients, and the number of bacterial species, while also exploring novel 3D biofilm models. The growth of biofilms on clinically relevant 3D models, particularly melt electrowritten fibrous scaffolds, is discussed with a specific focus that has not been previously reported. Relevant studies on validated oral microcosm models that have recently gaining prominence are summarized. The review analyses the advantages and limitations of biofilm assessment methods, including colony forming unit culture, crystal violet, 2,3‐bis‐(2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide inner salt assays, confocal microscopy, fluorescence in situ hybridization, scanning electron microscopy, quantitative polymerase chain reaction, and next‐generation sequencing. The use of more complex models with advanced assessment methodologies, subject to the availability of equipment/facilities, may help in developing clinically relevant biofilms and answering appropriate research questions.

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Quorum Sensing and Quorum Quenching with a Focus on Cariogenic and Periodontopathic Oral Biofilms

Cited by 29 publications

References 131 publications

The Antibacterial Effect of Cannabigerol toward Streptococcus mutans Is Influenced by the Autoinducers 21-CSP and AI-2

The Antibacterial Effect of Cannabigerol toward Streptococcus mutans Is Influenced by the Autoinducers 21-CSP and AI-2

An in vitro dynamic bioreactor model for evaluating antimicrobial effectiveness on periodontal polymicrobial biofilms: a proof‐of‐concept study

Evaluating models and assessment techniques for understanding oral biofilm complexity

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