Tolerance to the antimicrobial peptide colistin in Pseudomonas aeruginosa biofilms is linked to metabolically active cells, and depends on the pmr and mexAB‐oprM genes

  title={Tolerance to the antimicrobial peptide colistin in Pseudomonas aeruginosa biofilms is linked to metabolically active cells, and depends on the pmr and mexAB‐oprM genes},
  author={S{\"u}nje Johanna Pamp and Morten Gjermansen and Helle Krogh Johansen and Tim Tolker-Nielsen},
  journal={Molecular Microbiology},
Bacteria living as biofilm are frequently reported to exhibit inherent tolerance to antimicrobial compounds, and might therefore contribute to the persistence of infections. Antimicrobial peptides are attracting increasing interest as new potential antimicrobial therapeutics; however, little is known about potential mechanisms, which might contribute to resistance or tolerance development towards these compounds in biofilms. Here we provide evidence that a spatially distinct subpopulation of… 

The metabolically active subpopulation in Pseudomonas aeruginosa biofilms survives exposure to membrane-targeting antimicrobials via distinct molecular mechanisms.

It is found that membrane-targeting antimicrobials such as colistin, EDTA, SDS, and chlorhexidine specifically kill the inactive subpopulation in P. aeruginosa biofilms, whereas the active subpopulation survives exposure to these compounds.

Tolerance and Persistence of Pseudomonas aeruginosa in Biofilms Exposed to Antibiotics: Molecular Mechanisms, Antibiotic Strategies and Therapeutic Perspectives

The molecular mechanisms involved in antibiotic tolerance and persistence in P. aeruginosa biofilm infections are reviewed, showing that biofilm growth had an unequal impact of antibiotic activity, colistin and meropenem being the less impacted antibiotics.

Adaptive Resistance to the “Last Hope” Antibiotics Polymyxin B and Colistin in Pseudomonas aeruginosa Is Mediated by the Novel Two-Component Regulatory System ParR-ParS

ABSTRACT As multidrug resistance increases alarmingly, polymyxin B and colistin are increasingly being used in the clinic to treat serious Pseudomonas aeruginosa infections. In this opportunistic

Pseudomonas Aeruginosa: Resistance to the Max

The organism's propensity to grow in vivo as antimicrobial-tolerant biofilms and the occurrence of hypermutator strains that yield antimicrobial resistant mutants at higher frequency also compromise anti-pseudomonal chemotherapy.

Contribution of Stress Responses to Antibiotic Tolerance in Pseudomonas aeruginosa Biofilms

Results are consistent with a model in which multiple genes controlled by overlapping starvation or stress responses contribute to the protection of a P. aeruginosa biofilm from ciprofloxacin, a distinct and as yet undiscovered mechanism protects the biofilm bacteria from tobramycin.

Triclosan depletes the membrane potential in Pseudomonas aeruginosa biofilms inhibiting aminoglycoside induced adaptive resistance

It is demonstrated that in addition to its canonical mechanism inhibiting membrane biosynthesis, triclosan can exert antibacterial properties by functioning as a protonophore that targets P. aeruginosa energetics.

Antibiotic resistance of bacterial biofilms.

Selective Proteomic Analysis of Antibiotic-Tolerant Cellular Subpopulations in Pseudomonas aeruginosa Biofilms

The use of the bio-orthogonal noncanonical amino acid tagging (BONCAT) method is described to enable selective proteomic analysis of a Pseudomonas aeruginosa biofilm subpopulation, demonstrating how the study of proteome dynamics can enhance the authors' understanding of biofilm heterogeneity and antibiotic tolerance.

Pseudomonas aeruginosa Is More Tolerant Under Biofilm Than Under Planktonic Growth Conditions: A Multi-Isolate Survey

This study investigated a large and highly diverse collection of 352 clinical Pseudomonas aeruginosa isolates for their antimicrobial susceptibility profiles under biofilm growth conditions towards the antibiotics ciprofloxacin, tobramycin, and colistin, and discovered characteristic patterns of drug-specific killing activity and conditional tolerance levels far lower than generally believed.



Multidrug Efflux Pumps: Expression Patterns and Contribution to Antibiotic Resistance in Pseudomonas aeruginosa Biofilms

The surprising discovery that the four characterized efflux pumps do not play a role in the antibiotic-resistant phenotype of P. aeruginosa biofilm resistance is found.

Efflux as a mechanism of resistance to antimicrobials in Pseudomonas aeruginosa and related bacteria: unanswered questions.

  • H. Schweizer
  • Biology
    Genetics and molecular research : GMR
  • 2003
Homologues of the resistance-nodulation-division systems of P. aeruginosa have been found in Burkholderia cepacia, B. pseudomallei, Stenotrophomonas maltophilia, and the nonpathogen P. putida, where they play roles in resistance to antimicrobials and/or organic solvents.

Intrinsic Resistance to Inhibitors of Fatty Acid Biosynthesis in Pseudomonas aeruginosa Is Due to Efflux: Application of a Novel Technique for Generation of Unmarked Chromosomal Mutations for the Study of Efflux Systems

  • H. Schweizer
  • Biology
    Antimicrobial Agents and Chemotherapy
  • 1998
The experiments showed that the MexAB-OprM system is responsible for the intrinsic resistance of this bacterium to cerulenin and thiolactomycin and is capable of efflux of irgasan, a broad-spectrum antimicrobial compound used in media selective for Pseudomonas.

Multidrug efflux pumps and antimicrobial resistance in Pseudomonas aeruginosa and related organisms.

  • K. Poole
  • Biology
    Journal of molecular microbiology and biotechnology
  • 2001
Although the natural function of these multidrug efflux systems is largely unknown, their contribution to antibiotic resistance and their conservation in a number of important human pathogens makes them logical targets for therapeutic intervention.

Biofilms and Planktonic Cells of Pseudomonas aeruginosa Have Similar Resistance to Killing by Antimicrobials

The notion that biofilms have greater resistance than do planktonic cells is unwarranted, and it is suggested that tolerance to antibiotics in stationary-phase or biofilm cultures is largely dependent on the presence of persister cells.

A Dose-Response Study of Antibiotic Resistance in Pseudomonas aeruginosa Biofilms

Dose-dependent killing indicated the presence of a small “superresistant” cell fraction that was primarily responsible for very high resistance of P. aeruginosa biofilms to quinolones.

Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors

A synthetic derivate of natural furanone compounds can act as a potent antagonist of bacterial quorum sensing and inhibited virulence factor expression in a mouse pulmonary infection model.

Expression of Pseudomonas aeruginosa Multidrug Efflux Pumps MexA-MexB-OprM and MexC-MexD-OprJ in a Multidrug-Sensitive Escherichia coli Strain

It is confirmed that a tripartite efflux pump is necessary for the efflux of all substrate antibiotics and that the P. aeruginosa multidrug efflux pumps are functional and retain their substrate specificity in E. coli.

Differentiation and Distribution of Colistin- and Sodium Dodecyl Sulfate-Tolerant Cells in Pseudomonas aeruginosa Biofilms

Increased antibiotic tolerance in biofilms may be a consequence of differentiation into distinct subpopulations with different phenotypic properties, as suggested by mutations in genes interfering with lipopolysaccharide modification.

Cationic Antimicrobial Peptide Resistance in Neisseria meningitidis

Data indicated that meningococci utilize multiple mechanisms including the action of the MtrC-MtrD- MtrE efflux pump and lipid A modification as well as the type IV pilin secretion system to modulate levels of CAMP resistance.