Related Experiment Video

Updated: Mar 23, 2026

Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa
11:31

Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa

Published on: June 30, 2016

9.2K

Potentiation of Aminoglycoside Activity in Pseudomonas aeruginosa by Targeting the AmgRS Envelope Stress-Responsive

Keith Poole1, Christie Gilmour2, Maya A Farha3

  • 1Department of Biomedical and Molecular Sciences, Botterell Hall, Queen's University, Kingston, Ontario, Canada poolek@queensu.ca.

Antimicrobial Agents and Chemotherapy
|March 30, 2016
PubMed

Insights

Rifampin potentiates specific aminoglycosides against Pseudomonas aeruginosa by targeting the AmgRS system, offering potential for combination therapies against resistant infections.

Area of Science:

  • Microbiology
  • Pharmacology
  • Molecular Biology

Background:

  • Aminoglycosides (AGs) are crucial antibiotics, but resistance in Pseudomonas aeruginosa is a growing concern.
  • The AmgRS two-component system (TCS) is vital for P. aeruginosa to resist AGs by mitigating membrane damage.
  • Understanding mechanisms to overcome AG resistance is critical for effective treatment strategies.

Purpose of the Study:

  • To identify agents that enhance the activity of paromomycin (PAR), a 4,5-linked AG, against P. aeruginosa.
  • To elucidate the mechanism by which rifampin (RIF) potentiates AG activity.
  • To explore the potential of RIF as an adjuvant therapy for AG-resistant P. aeruginosa infections.

Main Methods:

  • Conducted a screen to identify agents potentiating PAR activity.
  • Tested RIF's potentiation of various AGs in wild-type and mutant P. aeruginosa strains.
  • Investigated the role of the AmgRS TCS and RNA polymerase in RIF's potentiation effect.
  • Assessed RIF's impact on AmgRS-dependent gene expression and MexXY efflux system activity.

Main Results:

  • Rifampin (RIF) potentiated 4,5-linked AGs (e.g., paromomycin, neomycin) but not 4,6-linked AGs (e.g., amikacin, gentamicin).
  • Potentiation was dependent on the AmgRS TCS and functional RNA polymerase.
  • RIF reduced the expression of some AmgRS-dependent genes but did not impair membrane protection.
  • RIF reversed AG resistance in clinical isolates, partly by downregulating the MexXY efflux system.

Conclusions:

  • RIF potentiates specific AGs by interfering with the AmgRS TCS and RNA polymerase function in P. aeruginosa.
  • RIF's ability to overcome AmgRS-mediated resistance, including MexXY efflux, highlights its potential as an adjuvant.
  • Combination therapy with RIF and AGs may offer a strategy to treat challenging P. aeruginosa infections.

More Related Videos

Generation of In-Frame Gene Deletion Mutants in Pseudomonas aeruginosa and Testing for Virulence Attenuation in a Simple Mouse Model of Infection08:34

Generation of In-Frame Gene Deletion Mutants in Pseudomonas aeruginosa and Testing for Virulence Attenuation in a Simple Mouse Model of Infection

Published on: January 8, 2020

7.4K
Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System05:06

Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System

Published on: January 5, 2024

1.2K

Related Concept Videos

Inhibitors of Bacterial Protein Synthesis01:25

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...
19
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,...
863
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and...
47
Stringent Response in E. coli01:23

Stringent Response in E. coli

Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
463
Global Regulatory Systems01:28

Global Regulatory Systems

Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
859
Inhibitors of Gram-positive Cell Wall Synthesis01:23

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
21