Related Experiment Video

Updated: May 19, 2026

Replication of the Ordered, Nonredundant Library of Pseudomonas aeruginosa strain PA14 Transposon Insertion Mutants
11:35

Replication of the Ordered, Nonredundant Library of Pseudomonas aeruginosa strain PA14 Transposon Insertion Mutants

Published on: May 4, 2018

Determinants of intrinsic aminoglycoside resistance in Pseudomonas aeruginosa

Thomas Krahn1, Christie Gilmour, Justin Tilak

  • 1Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.

Antimicrobial Agents and Chemotherapy
|August 22, 2012
PubMed

Insights

Researchers identified genes in Pseudomonas aeruginosa that, when disrupted, increase susceptibility to multiple aminoglycoside antibiotics. This finding sheds light on the complex mechanisms of antibiotic resistance in this bacterium.

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • Pseudomonas aeruginosa is an opportunistic pathogen known for its intrinsic resistance to many antibiotics.
  • Aminoglycosides are a class of antibiotics crucial for treating P. aeruginosa infections, but resistance is a growing concern.

Purpose of the Study:

  • To identify genes in P. aeruginosa that contribute to intrinsic resistance against multiple aminoglycoside antibiotics.
  • To understand the mechanisms underlying this resistance, focusing on cell envelope permeability and membrane integrity.

Main Methods:

  • Screening of a transposon insertion mutant library of P. aeruginosa for enhanced susceptibility to paromomycin.
  • Characterization of identified mutants using deletion analysis, gene complementation, and assessment of aminoglycoside uptake and cytoplasmic membrane potential.
  • Investigating the role of identified genes in both intrinsic and acquired resistance by testing clinical isolates.

Main Results:

  • Disruption of genes involved in lipid biosynthesis (lptA, faoA), phosphate uptake (pstB), two-component regulation (amgRS, PA2797-PA2798), and a gene of unknown function (PA0392) enhanced susceptibility to multiple aminoglycosides.
  • Increased susceptibility was not due to altered aminoglycoside permeation of the cell envelope.
  • Several mutants exhibited increased cytoplasmic membrane depolarization upon gentamicin exposure, suggesting increased membrane susceptibility to damage.
  • Combinations of gene deletions further increased aminoglycoside susceptibility, indicating complex interactions within the resistome.
  • Deletion of these genes reduced the high-level aminoglycoside resistance in clinical P. aeruginosa isolates.

Conclusions:

  • Several novel genes contribute to the intrinsic pan-aminoglycoside resistance of P. aeruginosa.
  • The resistance mechanism involves increased susceptibility of the cytoplasmic membrane to antibiotic-induced damage rather than reduced uptake.
  • These identified genes are important targets for understanding and potentially overcoming aminoglycoside resistance in P. aeruginosa, including in clinical settings.

More Related Videos

Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes08:58

Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes

Published on: March 3, 2023

Related Concept Videos

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 acquisition...
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...
Development of Antibiotic Resistance01:30

Development of Antibiotic Resistance

Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
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,...
Estimation of k and VD of Aminoglycosides01:20

Estimation of k and VD of Aminoglycosides

Aminoglycosides are a class of antibiotics used to treat various bacterial infections. Clinicians must determine the elimination rate constant (k) and volume of distribution (VD) to optimize therapeutic efficacy and minimize toxicity. The k value represents the rate at which the drug is removed from the body, and the VD reflects the degree to which the drug distributes into body tissues. Accurately estimating these parameters allows healthcare professionals to tailor drug dosing to individual...