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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/content/journal/micro/10.1099/mic.0.074203-0
2014-07-01
2021-05-14
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References

  1. Atkinson R. M., Lipuma J. J., Rosenbluth D. B., Dunne W. M. Jr ( 2006). Chronic colonization with Pandoraea apista in cystic fibrosis patients determined by repetitive-element-sequence PCR. J Clin Microbiol 44:833–836 [CrossRef][PubMed]
    [Google Scholar]
  2. Bamford S., Ryley H., Jackson S. K. ( 2007). Highly purified lipopolysaccharides from Burkholderia cepacia complex clinical isolates induce inflammatory cytokine responses via TLR4-mediated MAPK signalling pathways and activation of NFκB. Cell Microbiol 9:532–543 [CrossRef][PubMed]
    [Google Scholar]
  3. Bandara H. M., Yau J. Y., Watt R. M., Jin L. J., Samaranayake L. P. ( 2010). Pseudomonas aeruginosa inhibits in-vitro Candida biofilm development. BMC Microbiol 10:125 [CrossRef][PubMed]
    [Google Scholar]
  4. Banu O., Bleotu C., Chifiriuc M. C., Savu B., Stanciu G., Antal C., Alexandrescu M., Lazăr V. ( 2011). Virulence factors of Staphylococcus aureus and Pseudomonas aeruginosa strains involved in the etiology of cardiovascular infections. Biointerface Res Appl Chem 1:072–077
    [Google Scholar]
  5. Baysse C., De Vos D., Naudet Y., Vandermonde A., Ochsner U., Meyer J.-M., Budzikiewicz H., Schäfer M., Fuchs R., Cornelis P. ( 2000). Vanadium interferes with siderophore-mediated iron uptake in Pseudomonas aeruginosa . Microbiology 146:2425–2434[PubMed]
    [Google Scholar]
  6. Becerra M. C., Eraso A. J., Albesa I. ( 2003). Comparison of oxidative stress induced by ciprofloxacin and pyoverdin in bacteria and in leukocytes to evaluate toxicity. Luminescence 18:334–340 [CrossRef][PubMed]
    [Google Scholar]
  7. Bevivino A., Pirone L., Pilkington R., Cifani N., Dalmastri C., Callaghan M., Ascenzioni F., McClean S. ( 2012). Interaction of environmental Burkholderia cenocepacia strains with cystic fibrosis and non-cystic fibrosis bronchial epithelial cells in vitro . Microbiology 158:1325–1333 [CrossRef][PubMed]
    [Google Scholar]
  8. Bonfield T. L., Panuska J. R., Konstan M. W., Hilliard K. A., Hilliard J. B., Ghnaim H., Berger M. ( 1995). Inflammatory cytokines in cystic fibrosis lungs. Am J Respir Crit Care Med 152:2111–2118 [CrossRef][PubMed]
    [Google Scholar]
  9. Bragonzi A., Farulla I., Paroni M., Twomey K. B., Pirone L., Lorè N. I., Bianconi I., Dalmastri C., Ryan R. P., Bevivino A. ( 2012). Modelling co-infection of the cystic fibrosis lung by Pseudomonas aeruginosa and Burkholderia cenocepacia reveals influences on biofilm formation and host response. PLoS ONE 7:e52330 [CrossRef][PubMed]
    [Google Scholar]
  10. Bredenbruch F., Geffers R., Nimtz M., Buer J., Häussler S. ( 2006). The Pseudomonas aeruginosa quinolone signal (PQS) has an iron-chelating activity. Environ Microbiol 8:1318–1329 [CrossRef][PubMed]
    [Google Scholar]
  11. Caraher E., Collins J., Herbert G., Murphy P. G., Gallagher C. G., Crowe M. J., Callaghan M., McClean S. ( 2008). Evaluation of in vitro virulence characteristics of the genus Pandoraea in lung epithelial cells. J Med Microbiol 57:15–20 [CrossRef][PubMed]
    [Google Scholar]
  12. Coenye T., Falsen E., Hoste B., Ohlén M., Goris J., Govan J. R., Gillis M., Vandamme P. ( 2000). Description of Pandoraea gen. nov. with Pandoraea apista sp. nov., Pandoraea pulmonicola sp. nov., Pandoraea pnomenusa sp. nov., Pandoraea sputorum sp. nov. and Pandoraea norimbergensis comb. nov.. Int J Syst Evol Microbiol 50:887–899 [CrossRef][PubMed]
    [Google Scholar]
  13. Costello A., Herbert G., Fabunmi L., Schaffer K., Kavanagh K. A., Caraher E. M., Callaghan M., McClean S. ( 2011). Virulence of an emerging respiratory pathogen, genus Pandoraea, in vivo and its interactions with lung epithelial cells. J Med Microbiol 60:289–299 [CrossRef][PubMed]
    [Google Scholar]
  14. Courtney J. M., Dunbar K. E., McDowell A., Moore J. E., Warke T. J., Stevenson M., Elborn J. S. ( 2004). Clinical outcome of Burkholderia cepacia complex infection in cystic fibrosis adults. J Cyst Fibros 3:93–98 [CrossRef][PubMed]
    [Google Scholar]
  15. Cox M. J., Allgaier M., Taylor B., Baek M. S., Huang Y. J., Daly R. A., Karaoz U., Andersen G. L., Brown R. & other authors ( 2010). Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients. PLoS ONE 5:e11044 [CrossRef][PubMed]
    [Google Scholar]
  16. Daneshvar M. I., Hollis D. G., Steigerwalt A. G., Whitney A. M., Spangler L., Douglas M. P., Jordan J. G., MacGregor J. P., Hill B. C. & other authors ( 2001). Assignment of CDC weak oxidizer group 2 (WO-2) to the genus Pandoraea and characterization of three new Pandoraea genomospecies. J Clin Microbiol 39:1819–1826 [CrossRef][PubMed]
    [Google Scholar]
  17. De Soyza A., Meachery G., Hester K. L., Nicholson A., Parry G., Tocewicz K., Pillay T., Clark S., Lordan J. L. & other authors ( 2010). Lung transplantation for patients with cystic fibrosis and Burkholderia cepacia complex infection: a single-center experience. J Heart Lung Transplant 29:1395–1404 [CrossRef][PubMed]
    [Google Scholar]
  18. De Soyza A., Hall A. J., Mahenthiralingam E., Drevinek P., Kaca W., Drulis-Kawa Z., Stoitsova S. R., Toth V., Coenye T. & other authors ( 2013). Developing an international Pseudomonas aeruginosa reference panel. Microbiology Open 21010–1023 [CrossRef]
    [Google Scholar]
  19. Diggle S. P., Matthijs S., Wright V. J., Fletcher M. P., Chhabra S. R., Lamont I. L., Kong X., Hider R. C., Cornelis P. & other authors ( 2007). The Pseudomonas aeruginosa 4-quinolone signal molecules HHQ and PQS play multifunctional roles in quorum sensing and iron entrapment. Chem Biol 14:87–96 [CrossRef][PubMed]
    [Google Scholar]
  20. Drevinek P., Mahenthiralingam E. ( 2010). Burkholderia cenocepacia in cystic fibrosis: epidemiology and molecular mechanisms of virulence. Clin Microbiol Infect 16:821–830 [CrossRef][PubMed]
    [Google Scholar]
  21. Duan K., Sibley C. D., Davidson C. J., Surette M. G. ( 2009). Chemical interactions between organisms in microbial communities. Contrib Microbiol 16:1–17 [CrossRef][PubMed]
    [Google Scholar]
  22. Govan J. R., Brown A. R., Jones A. M. ( 2007). Evolving epidemiology of Pseudomonas aeruginosa and the Burkholderia cepacia complex in cystic fibrosis lung infection. Future Microbiol 2:153–164 [CrossRef][PubMed]
    [Google Scholar]
  23. Holcombe L. J., McAlester G., Munro C. A., Enjalbert B., Brown A. J., Gow N. A., Ding C., Butler G., O’Gara F., Morrissey J. P. ( 2010). Pseudomonas aeruginosa secreted factors impair biofilm development in Candida albicans . Microbiology 156:1476–1486 [CrossRef][PubMed]
    [Google Scholar]
  24. Jones A. M., Dodd M. E., Webb A. K.( 2001). Burkholderia cepacia: current clinical issues, environmental controversies and ethical dilemmas. Eur Respir J 17:295–301 [CrossRef]
    [Google Scholar]
  25. Jørgensen I. M., Johansen H. K., Frederiksen B., Pressler T., Hansen A., Vandamme P., Høiby N., Koch C. ( 2003). Epidemic spread of Pandoraea apista, a new pathogen causing severe lung disease in cystic fibrosis patients. Pediatr Pulmonol 36:439–446 [CrossRef][PubMed]
    [Google Scholar]
  26. Kaza S. K., McClean S., Callaghan M. ( 2011). IL-8 released from human lung epithelial cells induced by cystic fibrosis pathogens Burkholderia cepacia complex affects the growth and intracellular survival of bacteria. Int J Med Microbiol 301:26–33 [CrossRef][PubMed]
    [Google Scholar]
  27. Kim K., Kim S. H., Lépine F., Cho Y. H., Lee G. R. ( 2010a). Global gene expression analysis on the target genes of PQS and HHQ in J774A.1 monocyte/macrophage cells. Microb Pathog 49:174–180 [CrossRef][PubMed]
    [Google Scholar]
  28. Kim K., Kim Y. U., Koh B. H., Hwang S. S., Kim S. H., Lépine F., Cho Y. H., Lee G. R. ( 2010b). HHQ and PQS, two Pseudomonas aeruginosa quorum-sensing molecules, down-regulate the innate immune responses through the nuclear factor-κB pathway. Immunology 129:578–588 [CrossRef][PubMed]
    [Google Scholar]
  29. Lau G. W., Hassett D. J., Ran H., Kong F. ( 2004). The role of pyocyanin in Pseudomonas aeruginosa infection. Trends Mol Med 10:599–606 [CrossRef][PubMed]
    [Google Scholar]
  30. Laursen J. B., Nielsen J. ( 2004). Phenazine natural products: biosynthesis, synthetic analogues, and biological activity. Chem Rev 104:1663–1686 [CrossRef][PubMed]
    [Google Scholar]
  31. Lavigne J.-P., Nicolas-Chanoine M.-H., Bourg G., Moreau J., Sotto A. ( 2008). Virulent synergistic effect between Enterococcus faecalis and Escherichia coli assayed by using the Caenorhabditis elegans model. PLoS ONE 3:e3370 [CrossRef][PubMed]
    [Google Scholar]
  32. Legendre C., Reen F. J., Mooij M. J., McGlacken G. P., Adams C., O’Gara F. ( 2012). Pseudomonas aeruginosa alkyl quinolones repress hypoxia-inducible factor 1 (HIF-1) signaling through HIF-1α degradation. Infect Immun 80:3985–3992 [CrossRef][PubMed]
    [Google Scholar]
  33. Lewenza S., Visser M. B., Sokol P. A. ( 2002). Interspecies communication between Burkholderia cepacia and Pseudomonas aeruginosa . Can J Microbiol 48:707–716 [CrossRef][PubMed]
    [Google Scholar]
  34. Liberati N. T., Urbach J. M., Miyata S., Lee D. G., Drenkard E., Wu G., Villanueva J., Wei T., Ausubel F. M. ( 2006). An ordered, nonredundant library of Pseudomonas aeruginosa strain PA14 transposon insertion mutants. Proc Natl Acad Sci U S A 103:2833–2838 [CrossRef][PubMed]
    [Google Scholar]
  35. LiPuma J. J. ( 2010). The changing microbial epidemiology in cystic fibrosis. Clin Microbiol Rev 23:299–323 [CrossRef][PubMed]
    [Google Scholar]
  36. Machen T. E. ( 2006). Innate immune response in CF airway epithelia: hyperinflammatory?. Am J Physiol Cell Physiol 291:C218–C230 [CrossRef][PubMed]
    [Google Scholar]
  37. Mahenthiralingam E., Coenye T., Chung J. W., Speert D. P., Govan J. R., Taylor P., Vandamme P. ( 2000). Diagnostically and experimentally useful panel of strains from the Burkholderia cepacia complex. J Clin Microbiol 38:910–913[PubMed]
    [Google Scholar]
  38. Mahenthiralingam E., Song L., Sass A., White J., Wilmot C., Marchbank A., Boaisha O., Paine J., Knight D., Challis G. L. ( 2011). Enacyloxins are products of an unusual hybrid modular polyketide synthase encoded by a cryptic Burkholderia ambifaria genomic island. Chem Biol 18:665–677 [CrossRef][PubMed]
    [Google Scholar]
  39. Masyahit M., Sijam K., Awang Y., Satar M. G. M. ( 2009). In vitro assay of factors affecting the growth of pathogens associated with diseases on dragon fruit (Hylocereus spp.) in peninsular Malaysia. Plant Pathol J 8:144–151 [CrossRef]
    [Google Scholar]
  40. Mazzola M., Cook R. J., Thomashow L. S., Weller D. M., Pierson L. S. III ( 1992). Contribution of phenazine antibiotic biosynthesis to the ecological competence of fluorescent pseudomonads in soil habitats. Appl Environ Microbiol 58:2616–2624[PubMed]
    [Google Scholar]
  41. Medeiros A. A., O’Brien T. F., Wacker W. E., Yulug N. F. ( 1971). Effect of salt concentration on the apparent in-vitro susceptibility of Pseudomonas and other gram-negative bacilli to gentamicin. J Infect Dis 124:SupplS59–S64 [CrossRef][PubMed]
    [Google Scholar]
  42. Rahme L. G., Stevens E. J., Wolfort S. F., Shao J., Tompkins R. G., Ausubel F. M. ( 1995). Common virulence factors for bacterial pathogenicity in plants and animals. Science 268:1899–1902 [CrossRef][PubMed]
    [Google Scholar]
  43. Reen F. J., Mooij M. J., Holcombe L. J., McSweeney C. M., McGlacken G. P., Morrissey J. P., O’Gara F. ( 2011). The Pseudomonas quinolone signal (PQS), and its precursor HHQ, modulate interspecies and interkingdom behaviour. FEMS Microbiol Ecol 77:413–428 [CrossRef][PubMed]
    [Google Scholar]
  44. Reen F. J., Clarke S. L., Legendre C., McSweeney C. M., Eccles K. S., Lawrence S. E., O’Gara F., McGlacken G. P. ( 2012). Structure-function analysis of the C-3 position in analogues of microbial behavioural modulators HHQ and PQS. Org Biomol Chem 10:8903–8910 [CrossRef][PubMed]
    [Google Scholar]
  45. Riedel K., Hentzer M., Geisenberger O., Huber B., Steidle A., Wu H., Høiby N., Givskov M., Molin S., Eberl L. ( 2001). N-Acylhomoserine-lactone-mediated communication between Pseudomonas aeruginosa and Burkholderia cepacia in mixed biofilms. Microbiology 147:3249–3262[PubMed]
    [Google Scholar]
  46. Sahin N., Tani A., Kotan R., Sedlácek I., Kimbara K., Tamer A. U. ( 2011). Pandoraea oxalativorans sp. nov., Pandoraea faecigallinarum sp. nov. and Pandoraea vervacti sp. nov., isolated from oxalate-enriched culture. Int J Syst Evol Microbiol 61:2247–2253 [CrossRef][PubMed]
    [Google Scholar]
  47. Schneider I., Queenan A. M., Bauernfeind A. ( 2006). Novel carbapenem-hydrolyzing oxacillinase OXA-62 from Pandoraea pnomenusa . Antimicrob Agents Chemother 50:1330–1335 [CrossRef][PubMed]
    [Google Scholar]
  48. Sibley C. D., Duan K., Fischer C., Parkins M. D., Storey D. G., Rabin H. R., Surette M. G. ( 2008). Discerning the complexity of community interactions using a Drosophila model of polymicrobial infections. PLoS Pathog 4:e1000184 [CrossRef][PubMed]
    [Google Scholar]
  49. Sibley C. D., Grinwis M. E., Field T. R., Eshaghurshan C. S., Faria M. M., Dowd S. E., Parkins M. D., Rabin H. R., Surette M. G. ( 2011). Culture enriched molecular profiling of the cystic fibrosis airway microbiome. PLoS ONE 6:e22702 [CrossRef][PubMed]
    [Google Scholar]
  50. Stryjewski M. E., LiPuma J. J., Messier R. H. Jr, Reller L. B., Alexander B. D. ( 2003). Sepsis, multiple organ failure, and death due to Pandoraea pnomenusa infection after lung transplantation. J Clin Microbiol 41:2255–2257 [CrossRef][PubMed]
    [Google Scholar]
  51. Treat J., James W. D., Nachamkin I., Seykora J. T. ( 2007). Growth inhibition of Trichophyton species by Pseudomonas aeruginosa . Arch Dermatol 143:61–64 [CrossRef][PubMed]
    [Google Scholar]
  52. Visca P., Imperi F., Lamont I. L. ( 2007). Pyoverdine siderophores: from biogenesis to biosignificance. Trends Microbiol 15:22–30 [CrossRef][PubMed]
    [Google Scholar]
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