Inhibition of co-colonizing cystic fibrosis-associated pathogens by Pseudomonas aeruginosa and Burkholderia multivorans.
Cystic fibrosis (CF) is a recessive genetic disease characterized by chronic respiratory infections and inflammation causing permanent lung damage. Recurrent infections are caused by Gram-negative antibiotic-resistant bacterial pathogens such as Pseudomonas aeruginosa, Burkholderia cepacia complex (Bcc) and the emerging pathogen genus Pandoraea. In this study, the interactions between co-colonizing CF pathogens were investigated. Both Pandoraea and Bcc elicited potent pro-inflammatory responses that were significantly greater than Ps. aeruginosa. The original aim was to examine whether combinations of pro-inflammatory pathogens would further exacerbate inflammation. In contrast, when these pathogens were colonized in the presence of Ps. aeruginosa the pro-inflammatory response was significantly decreased. Real-time PCR quantification of bacterial DNA from mixed cultures indicated that Ps. aeruginosa significantly inhibited the growth of Burkholderia multivorans, Burkholderia cenocepacia, Pandoraea pulmonicola and Pandoraea apista, which may be a factor in its dominance as a colonizer of CF patients. Ps. aeruginosa cell-free supernatant also suppressed growth of these pathogens, indicating that inhibition was innate rather than a response to the presence of a competitor. Screening of a Ps. aeruginosa mutant library highlighted a role for quorum sensing and pyoverdine biosynthesis genes in the inhibition of B. cenocepacia. Pyoverdine was confirmed to contribute to the inhibition of B. cenocepacia strain J2315. B. multivorans was the only species that could significantly inhibit Ps. aeruginosa growth. B. multivorans also inhibited B. cenocepacia and Pa. apista. In conclusion, both Ps. aeruginosa and B. multivorans are capable of suppressing growth and virulence of co-colonizing CF pathogens.
Centre of Microbial Host Interactions, Centre of Applied Science for Health, Institute of Technology Tallaght, Old Blessington Road, Tallaght, Dublin 24, Ireland.
Anne
A
Costello
BIOMERIT Research Centre, Department of Microbiology, University College Cork, Ireland.
F Jerry
FJ
Reen
Curtin University, School of Biomedical Sciences, Perth, WA 6845, Australia.|BIOMERIT Research Centre, Department of Microbiology, University College Cork, Ireland.
Fergal
F
O'Gara
Centre of Microbial Host Interactions, Centre of Applied Science for Health, Institute of Technology Tallaght, Old Blessington Road, Tallaght, Dublin 24, Ireland.
Máire
M
Callaghan
Centre of Microbial Host Interactions, Centre of Applied Science for Health, Institute of Technology Tallaght, Old Blessington Road, Tallaght, Dublin 24, Ireland.
Siobhán
S
McClean
D019117:Burkholderia / Q000502:physiology*; D019121:Burkholderia Infections / Q000382:microbiology / Q000517:prevention & control*; D042602:Burkholderia cepacia complex / Q000254:growth & development; D042521:Burkholderiaceae / Q000254:growth & development*; D002460:Cell Line; D003550:Cystic Fibrosis / Q000382:microbiology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells; D006801:Humans; D008954:Models, Biological; D011552:Pseudomonas Infections / Q000382:microbiology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D053038:Quorum Sensing; D014774:Virulence
D016207:Cytokines