1887

Abstract

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 , complex (Bcc) and the emerging pathogen genus . In this study, the interactions between co-colonizing CF pathogens were investigated. Both and Bcc elicited potent pro-inflammatory responses that were significantly greater than . 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 the pro-inflammatory response was significantly decreased. Real-time PCR quantification of bacterial DNA from mixed cultures indicated that significantly inhibited the growth of , , and , which may be a factor in its dominance as a colonizer of CF patients. 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 mutant library highlighted a role for quorum sensing and pyoverdine biosynthesis genes in the inhibition of . Pyoverdine was confirmed to contribute to the inhibition of strain J2315. was the only species that could significantly inhibit growth. also inhibited and . In conclusion, both and are capable of suppressing growth and virulence of co-colonizing CF pathogens.

Funding
This study was supported by the:
  • Programme for Research in Third Level Institutions (PRTLI) Cycle 4
  • European Union Regional Development Plan
  • Irish Government National Development Plan 2007-2013
  • Science Foundation of Ireland (Award 09/RFP/BMT 2350, 12/TIDA/B2405, 12/TIDA/B2411 and 07/IN.1/B948)
  • Department of Agriculture, Fisheries and Food (Award FIRM 08/RDC/629 and FIRM/RSF/CoFoRD)
  • Environmental Protection Agency (Award EPA 2008-PhD/S-2)
  • Irish Research Council for Science, Engineering and Technology (Award RS/2010/2413 and PD/2011/2414)
  • European Commission (Award 607786, FP7-PEOPLE-2013-ITN, Marie Curie 256596, OCEAN2012, CP-TP-312184, 311975, FP7-KBBE-2012-6 and 287589)
  • Marine Institute (Award C2CRA 2007/082)
  • Teagasc
  • Health Research Board (Award HRA/2009/146)
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2014-07-01
2024-03-28
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