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Bacterial cis-2-unsaturated fatty acids found in the cystic fibrosis airway modulate virulence and persistence of Pseudomonas aeruginosa
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Bacterial cis-2-unsaturated fatty acids found in the cystic fibrosis airway modulate virulence and persistence of Pseudomonas aeruginosa
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Journal Article
Bacterial cis-2-unsaturated fatty acids found in the cystic fibrosis airway modulate virulence and persistence of Pseudomonas aeruginosa
2012
Overview
There is an increasing appreciation of the polymicrobial nature of many bacterial infections such as those associated with cystic fibrosis (CF) and of the potentially important role for interspecies interactions in influencing both bacterial virulence and response to therapy. Patients with CF are often co-infected with
Pseudomonas aeruginosa
and other pathogens including
Burkholderia cenocepacia
and
Stenotrophomonas maltophilia
. These latter bacteria produce signal molecules of the diffusible signal factor (DSF) family, which are
cis
-2-unsaturated fatty acids. We have previously shown by
in vitro
studies that DSF from
S. maltophilia
leads to altered biofilm formation and increased resistance to antibiotics by
P. aeruginosa
; these responses of
P. aeruginosa
require the sensor kinase PA1396. Here we show that DSF signals are present in sputum taken from patients with CF. Presence of these DSF signals was correlated with patient colonization by
S. maltophilia
and/or
B. cenocepacia
. Analysis of 50 clinical isolates of
P. aeruginosa
showed that each responded to the presence of synthetic DSF by increased antibiotic resistance and these strains demonstrated little sequence variation in the PA1396 gene. In animal experiments using CF transmembrane conductance regulator knockout mice, the presence of DSF promoted
P. aeruginosa
persistence. Furthermore, antibiotic resistance of
P. aeruginosa
biofilms grown on human airway epithelial cells was enhanced in the presence of DSF. Taken together, these data provide substantial evidence that interspecies DSF-mediated bacterial interactions occur in the CF lung and may influence the efficacy of antibiotic treatment, particularly for chronic infections involving persistence of bacteria.
Publisher
Nature Publishing Group UK,Oxford University Press,Nature Publishing Group
Subject
/ Antimicrobial Cationic Peptides - pharmacology
/ Bacteria
/ Biofilms
/ Biomedical and Life Sciences
/ Burkholderia cenocepacia - drug effects
/ Burkholderia cenocepacia - pathogenicity
/ Burkholderia Infections - microbiology
/ Cystic Fibrosis - microbiology
/ Cystic Fibrosis Transmembrane Conductance Regulator - genetics
/ Ecology
/ Epithelial Cells - microbiology
/ Fatty Acids, Unsaturated - isolation & purification
/ Fatty Acids, Unsaturated - pharmacology
/ Female
/ Humans
/ Kinases
/ Lung
/ Mice
/ Microbial Genetics and Genomics
/ Original
/ Patients
/ Pseudomonas aeruginosa - drug effects
/ Pseudomonas aeruginosa - genetics
/ Pseudomonas aeruginosa - pathogenicity
/ Pseudomonas Infections - microbiology
/ Sputum
/ Stenotrophomonas maltophilia
/ Stenotrophomonas maltophilia - drug effects
