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Related Concept Videos

Gene Regulation in Microbial Communities: Quorum Sensing01:28

Gene Regulation in Microbial Communities: Quorum Sensing

Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
Bacterial Signaling01:30

Bacterial Signaling

Bacterial signaling can occur within bacteria (intracellular) or between bacteria (intercellular). At times, a group of bacteria behaves like a community. To achieve this, they engage in quorum sensing, the perception of higher cell density that causes changes in gene expression. Quorum sensing involves both extracellular and intracellular signaling. The signaling cascade starts with a molecule called an autoinducer (AI). Individual bacteria produce AIs that move out of the bacterial cell...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
Combined Effects of Drugs: Synergism01:27

Combined Effects of Drugs: Synergism

Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
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Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...

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Quantification of Violacein in Chromobacterium violaceum and Its Inhibition by Bioactive Compounds
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Interactions among quorum sensing inhibitors.

Rajat Anand1, Navneet Rai, Mukund Thattai

  • 1National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.

Plos One
|April 30, 2013
PubMed
Summary

Targeting bacterial quorum sensing (QS) with inhibitors offers new antimicrobial strategies. A computational model shows that combining LuxI and non-competitive LuxR inhibitors is the most effective therapeutic approach against virulence.

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Area of Science:

  • Microbiology
  • Computational Biology
  • Pharmacology

Background:

  • Pathogenic bacteria utilize quorum sensing (QS) systems to control virulence gene expression.
  • A common QS mechanism involves LuxI enzyme producing acyl-homoserine lactone (AHL) molecules, which activate the LuxR transcription factor at high bacterial densities.
  • Antibiotic resistance drives the search for novel therapies targeting bacterial QS.

Purpose of the Study:

  • To investigate the efficacy of individual and combined QS inhibitors using a computational model.
  • To analyze the impact of transcriptional feedback on QS regulation and inhibitor effectiveness.
  • To identify robust therapeutic strategies against bacterial virulence.

Main Methods:

  • Development and utilization of an experimentally validated computational model of the LuxI/LuxR QS system.
  • Inclusion of transcriptional feedback mechanisms to simulate non-linear responses to inhibitors.
  • Simulation of various inhibitor strategies, including LuxI and LuxR inhibitors (competitive and non-competitive).

Main Results:

  • For LuxI-feedback systems, LuxI inhibitors are more effective individually than LuxR inhibitors.
  • Competitive LuxR inhibitors can paradoxically increase virulence by weakly activating LuxR.
  • A combination of LuxI inhibitors and non-competitive LuxR inhibitors demonstrates multiplicative effects across a wide parameter range.

Conclusions:

  • The combination of LuxI inhibitors and non-competitive LuxR inhibitors represents a robust therapeutic strategy against bacterial virulence.
  • Understanding QS system dynamics, including feedback loops, is crucial for designing effective antimicrobial treatments.
  • Targeting QS offers a promising alternative to traditional antibiotics in combating resistant pathogens.