title: Bacterial cis-2-unsaturated fatty acids found in the cystic fibrosis airway modulate virulence and persistence of Pseudomonas aeruginosa.
abstract: 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.
authors: BIOMERIT Research Centre, Department of Microbiology, Biosciences Institute, University College Cork, Cork, Ireland.
authors: Kate B
authors: KB
authors: Twomey
authors: Oisin J
authors: OJ
authors: O'Connell
authors: Yvonne
authors: Y
authors: McCarthy
authors: J Maxwell
authors: JM
authors: Dow
authors: George A
authors: GA
authors: O'Toole
authors: Barry J
authors: BJ
authors: Plant
authors: Robert P
authors: RP
authors: Ryan
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D019121:Burkholderia Infections / Q000382:microbiology; D057508:Burkholderia cenocepacia / Q000187:drug effects / Q000472:pathogenicity; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000382:microbiology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D024881:Drug Resistance, Bacterial; D004847:Epithelial Cells / Q000382:microbiology; D005231:Fatty Acids, Unsaturated / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D015398:Signal Transduction; D013183:Sputum / Q000737:chemistry; D020615:Stenotrophomonas maltophilia / Q000187:drug effects / Q000472:pathogenicity; D014774:Virulence / Q000187:drug effects
chemical_list: D023181:Antimicrobial Cationic Peptides; D005231:Fatty Acids, Unsaturated; D019005:Cystic Fibrosis Transmembrane Conductance Regulator