Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms

  title={Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms},
  author={Pradeep K. Singh and Amy L. Schaefer and Matthew R. Parsek and Thomas O. Moninger and Michael J. Welsh and E. Peter Greenberg},
The bacterium Pseudomonas aeruginosa permanently colonizes cystic fibrosis lungs despite aggressive antibiotic treatment. This suggests that P. aeruginosa might exist as biofilms—structured communities of bacteria encased in a self-produced polymeric matrix—in the cystic fibrosis lung. Consistent with this hypothesis, microscopy of cystic fibrosis sputum shows that P. aeruginosa are in biofilm-like structures. P. aeruginosa uses extracellular quorum-sensing signals (extracellular chemical… 
Lectin-mediated biofilm maturation, quorum sensing and Pseudomonas aeruginosa infections in cystic fibrosis
The overall aim of this project was to elucidate some of the molecular mechanisms governing the pathogenesis of P. aeruginosa in the cystic fibrosis lung with particular reference to quorum sensing, a cell-to-cell communication system controlling the production of virulence determinants in a population density dependent manner using diffusible signal molecules.
Does Pseudomonas aeruginosa use intercellular signalling to build biofilm communities?
Quorum sensing regulates the expression of several secreted virulence factors and quorum sensing mutant strains are attenuated for virulence in animal models.
Impairment of Pseudomonas aeruginosa Biofilm Resistance to Antibiotics by Combining the Drugs with a New Quorum-Sensing Inhibitor
This study demonstrates that C11 may increase the efficacy of treatments for P. aeruginosa infections by increasing the susceptibility of biofilms to antibiotics and by attenuating the pathogenicity of the bacterium.
Calcium-Induced Virulence Factors Associated with the Extracellular Matrix of Mucoid Pseudomonas aeruginosa Biofilms
It is demonstrated that calcium addition affects the structure and extracellular matrix composition of mucoid P. aeruginosa biofilms, through increased expression and stability of bacterial extrace cellular products.
The role of quorum sensing in chronic cystic fibrosis Pseudomonas aeruginosa infections.
The evidence for a continuing role for QS in P. aeruginosa CF infections is discussed, including QS activity in CF sputa and CF-relevant effects of QS-regulated products, such as pyocyanin.
Cystic Fibrosis Sputum Supports Growth and Cues Key Aspects of Pseudomonas aeruginosa Physiology
It is indicated that CF sputum readily supports high-density P. aeruginosa growth and multiple signals, which reduce swimming motility and prematurely activate the Pseudomonas quinolone signal cell-to-cell signaling cascade in P. Aerug inosa, are present in CF spUTum.
Pseudomonas aeruginosa chronic colonization in cystic fibrosis patients
This review discusses recent advances regarding P. aeruginosa pathogenesis and biofilm behavior in the setting of chronic pulmonary disease and promising new therapies that target biofilm formation include molecules that disrupt quorum sensing.
Pseudomonas aeruginosa Forms Biofilms in Acute Infection Independent of Cell-to-Cell Signaling
It is shown that the opportunistic pathogen Pseudomonas aeruginosa forms biofilms within 8 h of infection in thermally injured mice, demonstrating that biofilmms contribute to bacterial colonization in acute infections as well.
In Vitro Analysis of Tobramycin-Treated Pseudomonas aeruginosa Biofilms on Cystic Fibrosis-Derived Airway Epithelial Cells
A tissue culture system for growth of P. aeruginosa biofilms on CF-derived human airway cells that promotes the formation of highly antibiotic-resistant microcolonies and identified the gene PA0913, which is upregulated by tobramycin specifically in bio films grown on CF airway Cells and codes for a probable magnesium transporter, MgtE.


The etiology and persistence of cryptic bacterial infections: a hypothesis.
  • J. Costerton
  • Biology, Medicine
    Reviews of infectious diseases
  • 1984
Antibiotics used to treat sequestered infections should be tested against populations of pathogens in intact biofilms to determine the ability of the antibiotics to penetrate the glycocalyces and to kill the component bacteria.
The involvement of cell-to-cell signals in the development of a bacterial biofilm.
The involvement of an intercellular signal molecule in the development of Pseudomonas aeruginosa biofilms suggests possible targets to control biofilm growth on catheters, in cystic fibrosis, and in other environments where P. aerug inosaBiofilms are a persistent problem.
The role of the microcolony mode of growth in the pathogenesis of Pseudomonas aeruginosa infections.
It is important to define the mode of bacterial growth in each type of P. aeruginosa infection and to understand the chemistry of the enveloping exopolysaccharide in order to limit its synthesis and/or facilitate its penetration by antibodies and antibiotics.
Contribution of the regulatory gene lasR to the pathogenesis of Pseudomonas aeruginosa infection of burned mice.
Results suggest that the lasR gene contributes (directly and indirectly) to the dissemination of P aeruginosa within the body of burned mice and its horizontal spread within the burned skin.
Contribution of specific Pseudomonas aeruginosa virulence factors to pathogenesis of pneumonia in a neonatal mouse model of infection
The expression of several P. aeruginosa virulence factors appears to be required to establish pulmonary infection in the neonatal mouse, as might be present in certain pathological conditions.
Identification of genes controlled by quorum sensing in Pseudomonas aeruginosa.
A library of random insertions in the chromosome of a P. aeruginosa acyl-HSL synthesis mutant was constructed by using a transposon containing a promoterless lacZ and thirty-nine quorum sensing-regulated genes were identified.
Exopolysaccharide production in biofilms: substratum activation of alginate gene expression by Pseudomonas aeruginosa
Reporter gene technology was employed to detect the activity of an alginate promoter of Pseudomonas aeruginosa when the organism was grown as a biofilm on a Teflon mesh substratum and as planktonic
Structure of the autoinducer required for expression of Pseudomonas aeruginosa virulence genes.
The elucidation of the PAI structure suggests therapeutic approaches toward control of P. aeruginosa infections and is shown to have chemical and biological properties identical to those of PAI purified from culture supernatant fluids.
Aminoglycoside penetration, inactivation, and efficacy in cystic fibrosis sputum.
It is concluded that tobramycin penetrates cystic fibrosis sputum and accumulates over time and 3 wk of intravenous therapy combined with an antipseudomonal beta-lactam antibiotic may be effective in eradication of P. aeruginosa fromSputum of certain CF patients.
Bacterial biofilms: a common cause of persistent infections.
Improvements in understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.