1887

Abstract

is a major pathogen in chronic lung diseases such as cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis (nCFB). Much of our understanding regarding infections in nCFB patients is extrapolated from findings in CF with little direct investigation on the adaptation of in nCFB patients. As such, we investigated whether the adaptation of was indeed similar between nCFB and CF. From our prospectively collected biobank, we identified 40 nCFB patients who had repeated isolates separated by ≥6 months and compared these to a control population of 28 CF patients. A total of 84 nCFB isolates [40 early (defined as the earliest isolate in the biobank) and 41 late (defined as the last available isolate in the biobank)] were compared to 83 CF isolates (39 early and 44 late). We assessed the isolates for protease, lipase and elastase production; mucoid phenotype; swarm and swim motility; biofilm production; and the presence of the mutant phenotype. Overall, we observed phenotypic heterogeneity in both nCFB and CF isolates and found that adapted to the nCFB lung environment similarly to the way observed in CF isolates in terms of protease and elastase expression, motility and biofilm formation. However, significant differences between nCFB and CF isolates were observed in lipase expression, which may allude to distinct characteristics found in the lung environment of nCFB patients. We also sought to determine virulence potential over time in nCFB isolates and found that virulence decreased over time, similar to CF.

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2016-12-21
2019-12-15
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References

  1. Al-Shirawi N., Al-Jahdall H., Al Shimemeri A.. 2006; Pathogenesis, etiology and treatment of bronchiectasis. Ann Thorac Med1:41–51[CrossRef]
    [Google Scholar]
  2. Barker A. F., Bardana E. J.. 1988; Bronchiectasis: update of an orphan disease. Am Rev Respir Dis137:969–978 [CrossRef][PubMed]
    [Google Scholar]
  3. Barker A. F., O'Donnell A. E., Flume P., Thompson P. J., Ruzi J. D., de Gracia J., Boersma W. G., De Soyza A., Shao L. et al. 2014; Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2): two randomised double-blind, placebo-controlled phase 3 trials. Lancet Respir Med2:738–749 [CrossRef][PubMed]
    [Google Scholar]
  4. Barth A. L., Pitt T. L.. 1996; The high amino-acid content of sputum from cystic fibrosis patients promotes growth of auxotrophic Pseudomonas aeruginosa. J Med Microbiol45:110–119 [CrossRef][PubMed]
    [Google Scholar]
  5. Bergin D. A., Hurley K., Mehta A., Cox S., Ryan D., O'Neill S. J., Reeves E. P., McElvaney N. G.. 2013; Airway inflammatory markers in individuals with cystic fibrosis and non-cystic fibrosis bronchiectasis. J Inflamm Res6:1–11 [CrossRef][PubMed]
    [Google Scholar]
  6. Ceri H., Olson M. E., Stremick C., Read R. R., Morck D., Buret A.. 1999; The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol37:1771–1776[PubMed]
    [Google Scholar]
  7. Chalmers J. D., Hill A. T.. 2013; Mechanisms of immune dysfunction and bacterial persistence in non-cystic fibrosis bronchiectasis. Mol Immunol55:27–34 [CrossRef][PubMed]
    [Google Scholar]
  8. Clark S. T., Diaz Caballero J., Cheang M., Coburn B., Wang P. W., Donaldson S. L., Zhang Y., Liu M., Keshavjee S. et al. 2015; Phenotypic diversity within a Pseudomonas aeruginosa population infecting an adult with cystic fibrosis. Sci Rep5:10932 [CrossRef][PubMed]
    [Google Scholar]
  9. Cowell B. A., Twining S. S., Hobden J. A., Kwong M. S., Fleiszig S. M.. 2003; Mutation of lasA and lasB reduces Pseudomonas aeruginosa invasion of epithelial cells. Microbiology149:2291–2299 [CrossRef][PubMed]
    [Google Scholar]
  10. Cystic Fibrosis Foundation 2015; Cystic Fibrosis Foundation Patient Registry 2014 Annual Data Report Bethesda, MD. https://www.cff.org/Our-Research/CF-Patient-Registry/Highlights-of-the-2014-Patient-Registry-Data/
    [Google Scholar]
  11. D'Argenio D. A., Wu M., Hoffman L. R., Kulasekara H. D., Déziel E., Smith E. E., Nguyen H., Ernst R. K., Larson Freeman T. J. et al. 2007; Growth phenotypes of Pseudomonas aeruginosa lasR mutants adapted to the airways of cystic fibrosis patients. Mol Microbiol64:512–533 [CrossRef][PubMed]
    [Google Scholar]
  12. Déziel E., Comeau Y., Villemur R.. 2001; Initiation of biofilm formation by Pseudomonas aeruginosa 57RP correlates with emergence of hyperpiliated and highly adherent phenotypic variants deficient in swimming, swarming, and twitching motilities. J Bacteriol183:1195–1204 [CrossRef][PubMed]
    [Google Scholar]
  13. Drake D., Montie T. C.. 1988; Flagella, motility and invasive virulence of Pseudomonas aeruginosa. J Gen Microbiol134:43–52 [CrossRef][PubMed]
    [Google Scholar]
  14. Drenkard E., Ausubel F. M.. 2002; Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Nature416:740–743 [CrossRef][PubMed]
    [Google Scholar]
  15. Drobnic M. E., Suñé P., Montoro J. B., Ferrer A., Orriols R.. 2005; Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa. Ann Pharmacother39:39–44 [CrossRef][PubMed]
    [Google Scholar]
  16. Duong J., Booth S. C., McCartney N. K., Rabin H. R., Parkins M. D., Storey D. G.. 2015; Phenotypic and genotypic comparison of epidemic and non-epidemic strains of Pseudomonas aeruginosa from individuals with cystic fibrosis. PLoS One10:e0143466 [CrossRef]
    [Google Scholar]
  17. Emerson J., Rosenfeld M., McNamara S., Ramsey B., Gibson R. L.. 2002; Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr Pulmonol34:91–100 [CrossRef][PubMed]
    [Google Scholar]
  18. Evans S. A., Turner S. M., Bosch B. J., Hardy C. C., Woodhead M. A.. 1996; Lung function in bronchiectasis: the influence of Pseudomonas aeruginosa. Eur Respir J9:1601–1604 [CrossRef][PubMed]
    [Google Scholar]
  19. Foweraker J. E., Laughton C. R., Brown D. F., Bilton D.. 2005; Phenotypic variability of Pseudomonas aeruginosa in sputa from patients with acute infective exacerbation of cystic fibrosis and its impact on the validity of antimicrobial susceptibility testing. J Antimicrob Chemother55:921–927 [CrossRef][PubMed]
    [Google Scholar]
  20. Gambello M. J., Iglewski B. H.. 1991; Cloning and characterization of the Pseudomonas aeruginosa lasR gene, a transcriptional activator of elastase expression. J Bacteriol173:3000–3009 [CrossRef][PubMed]
    [Google Scholar]
  21. Gellatly S. L., Needham B., Madera L., Trent M. S., Hancock R. E.. 2012; The Pseudomonas aeruginosa PhoP–PhoQ two-component regulatory system is induced upon interaction with epithelial cells and controls cytotoxicity and inflammation. Infect Immun80:3122–3131 [CrossRef][PubMed]
    [Google Scholar]
  22. Gillham M. I., Sundaram S., Laughton C. R., Haworth C. S., Bilton D., Foweraker J. E.. 2009; Variable antibiotic susceptibility in populations of Pseudomonas aeruginosa infecting patients with bronchiectasis. J Antimicrob Chemother63:728–732 [CrossRef][PubMed]
    [Google Scholar]
  23. Girod S., Zahm J. M., Plotkowski C., Beck G., Puchelle E.. 1992; Role of the physiochemical properties of mucus in the protection of the respiratory epithelium. Eur Respir J5:477–487[PubMed]
    [Google Scholar]
  24. Goeminne P. C., Scheers H., Decraene A., Seys S., Dupont L. J.. 2012; Risk factors for morbidity and death in non-cystic fibrosis bronchiectasis: a retrospective cross-sectional analysis of CT diagnosed bronchiectatic patients. Respir Res13:21 [CrossRef][PubMed]
    [Google Scholar]
  25. Gupta A. K., Lodha R., Kabra S. K.. 2015; Non cystic fibrosis bronchiectasis. Indian J Pediatr82:938–944 [CrossRef][PubMed]
    [Google Scholar]
  26. Harmer C., Alnassafi K., Hu H., Elkins M., Bye P., Rose B., Cordwell S., Triccas J. A., Harbour C. et al. 2013; Modulation of gene expression by Pseudomonas aeruginosa during chronic infection in the adult cystic fibrosis lung. Microbiology159:2354–2363 [CrossRef][PubMed]
    [Google Scholar]
  27. Heurlier K., Dénervaud V., Haenni M., Guy L., Krishnapillai V., Haas D.. 2005; Quorum-sensing-negative (lasR) mutants of Pseudomonas aeruginosa avoid cell lysis and death. J Bacteriol187:4875–4883 [CrossRef][PubMed]
    [Google Scholar]
  28. Ho P. L., Chan K. N., Ip M. S., Lam W. K., Ho C. S., Yuen K. Y., Tsang K. W.. 1998; The effect of Pseudomonas aeruginosa infection on clinical parameters in steady-state bronchiectasis. Chest114:1594–1598 [CrossRef][PubMed]
    [Google Scholar]
  29. Hoffman L. R., Kulasekara H. D., Emerson J., Houston L. S., Burns J. L., Ramsey B. W., Miller S. I.. 2009; Pseudomonas aeruginosa lasR mutants are associated with cystic fibrosis lung disease progression. J Cyst Fibros8:66–70 [CrossRef][PubMed]
    [Google Scholar]
  30. Hogardt M., Heesemann J.. 2013; Microevolution of Pseudomonas aeruginosa to a chronic pathogen of the cystic fibrosis lung. Curr Top Microbiol Immunol358:91–118 [CrossRef][PubMed]
    [Google Scholar]
  31. Kang Y., Nguyen D. T., Son M. S., Hoang T. T.. 2008; The Pseudomonas aeruginosa PsrA responds to long-chain fatty acid signals to regulate the fadBA5 β-oxidation operon. Microbiology154:1584–1598 [CrossRef][PubMed]
    [Google Scholar]
  32. Kerem E., Corey M., Gold R., Levison H.. 1990; Pulmonary function and clinical course in patients with cystic fibrosis after pulmonary colonization with Pseudomonas aeruginosa. J Pediatr116:714–719 [CrossRef][PubMed]
    [Google Scholar]
  33. King P. T., Holdsworth S. R., Freezer N. J., Villanueva E., Holmes P. W.. 2006; Characterisation of the onset and presenting clinical features of adult bronchiectasis. Respir Med100:2183–2189 [CrossRef][PubMed]
    [Google Scholar]
  34. King P. T., Holdsworth S. R., Freezer N. J., Villanueva E., Holmes P. W.. 2007; Microbiologic follow-up study in adult bronchiectasis. Respir Med101:1633–1638 [CrossRef][PubMed]
    [Google Scholar]
  35. Kohler T., Curty L. K., Barja F., van Delden C., Pechere J.-C.. 2000; Swarming of Pseudomonas aeruginosa is dependent on cell-to-cell signaling and requires flagella and pili. J Bacteriol182:5990–5996 [CrossRef][PubMed]
    [Google Scholar]
  36. Kosorok M. R., Zeng L., West S. E., Rock M. J., Splaingard M. L., Laxova A., Green C. G., Collins J., Farrell P. M.. 2001; Acceleration of lung disease in children with cystic fibrosis after Pseudomonas aeruginosa acquisition. Pediatr Pulmonol32:277–287 [CrossRef][PubMed]
    [Google Scholar]
  37. Kuang Z., Hao Y., Walling B. E., Jeffries J. L., Ohman D. E., Lau G. W.. 2011; Pseudomonas aeruginosa elastase provides an escape from phagocytosis by degrading the pulmonary surfactant protein-A. PLoS One6:e27091 [CrossRef][PubMed]
    [Google Scholar]
  38. LaFayette S. L., Houle D., Beaudoin T., Wojewodka G., Radzioch D., Hoffman L. R., Burns J. L., Dandekar A. A., Smalley N. E. et al. 2015; Cystic fibrosis-adapted Pseudomonas aeruginosa quorum sensing lasR mutants cause hyperinflammatory responses. Sci Adv1:e1500199 [CrossRef][PubMed]
    [Google Scholar]
  39. Li Z., Kosorok M. R., Farrell P. M., Laxova A., West S. E., Green C. G., Collins J., Rock M. J., Splaingard M. L.. 2005; Longitudinal development of mucoid Pseudomonas aeruginosa infection and lung disease progression in children with cystic fibrosis. JAMA293:581–588 [CrossRef][PubMed]
    [Google Scholar]
  40. Lonon M. K., Woods D. E., Straus D. C.. 1988; Production of lipase by clinical isolates Pseudomonas cepacia. J Clinic Microbiol26:979–984
    [Google Scholar]
  41. Lorè N. I., Cigana C., De Fino I., Riva C., Juhas M., Schwager S., Eberl L., Bragonzi A.. 2012; Cystic fibrosis-niche adaptation of Pseudomonas aeruginosa reduces virulence in multiple infection hosts. PLoS One7:e35648 [CrossRef]
    [Google Scholar]
  42. Luján A. M., Moyano A. J., Segura I., Argaraña C. E., Smania A. M.. 2007; Quorum-sensing-deficient (lasR) mutants emerge at high frequency from a Pseudomonas aeruginosa mutS strain. Microbiology153:225–237 [CrossRef][PubMed]
    [Google Scholar]
  43. Mah T. F., Pitts B., Pellock B., Walker G. C., Stewart P. S., O'Toole G. A.. 2003; A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature426:306–310 [CrossRef][PubMed]
    [Google Scholar]
  44. Martens C. J., Inglis S. K., Valentine V. G., Garrison J., Conner G. E., Ballard S. T.. 2011; Mucous solids and liquid secretion by airways: studies with normal pig, cystic fibrosis human, and non-cystic fibrosis human bronchi. Am J Physiol Lung Cell Mol Physiol301:L236–L246 [CrossRef][PubMed]
    [Google Scholar]
  45. Mathee K., Narasimhan G., Valdes C., Qiu X., Matewish J. M., Koehrsen M., Rokas A., Yandava C. N., Engels R. et al. 2008; Dynamics of Pseudomonas aeruginosa genome evolution. Proc Natl Acad Sci USA105:3100–3105 [CrossRef][PubMed]
    [Google Scholar]
  46. McShane P. J., Naureckas E. T., Strek M. E.. 2012; Bronchiectasis in a diverse US population: effects of ethnicity on etiology and sputum culture. Chest142:159–167 [CrossRef][PubMed]
    [Google Scholar]
  47. Mhanna M. J., Ferkol T., Martin R. J., Dreshaj I. A., van Heeckeren A. M., Kelley T. J., Haxhiu M. A.. 2001; Nitric oxide deficiency contributes to impairment of airway relaxation in cystic fibrosis mice. Am J Respir Cell Mol Biol24:621–626 [CrossRef][PubMed]
    [Google Scholar]
  48. Murray T. S., Kazmierczak B. I.. 2006; FlhF is required for swimming and swarming in Pseudomonas aeruginosa. J Bacteriol188:6995–7004 [CrossRef][PubMed]
    [Google Scholar]
  49. Nomura K., Obata K., Keira T., Miyata R., Hirakawa S., Takano K., Kohno T., Sawada N., Himi T. et al. 2014; Pseudomonas aeruginosa elastase causes transient disruption of tight junctions and downregulation of PAR-2 in human nasal epithelial cells. Respir Res15:21 [CrossRef][PubMed]
    [Google Scholar]
  50. O'Donnell A. E., Barker A. F., Ilowite J. S., Fick R. B.. 1998; Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I. Chest113:1329–1334[PubMed][CrossRef]
    [Google Scholar]
  51. O'Toole G. A., Kolter R.. 1998; Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol Microbiol30:295–304 [CrossRef][PubMed]
    [Google Scholar]
  52. Oliver A., Cantón R., Campo P., Baquero F., Blázquez J.. 2000; High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science288:1251–1254 [CrossRef][PubMed]
    [Google Scholar]
  53. Parkins M. D., Glezerson B. A., Sibley C. D., Sibley K. A., Duong J., Purighalla S., Mody C. H., Workentine M. L., Storey D. G. et al. 2014; Twenty-five-year outbreak of Pseudomonas aeruginosa infecting individuals with cystic fibrosis: identification of the prairie epidemic strain. J Clin Microbiol52:1127–1135 [CrossRef][PubMed]
    [Google Scholar]
  54. Pasteur M. C., Helliwell S. M., Houghton S. J., Webb S. C., Foweraker J. E., Coulden R. A., Flower C. D., Bilton D., Keogan M. T.. 2000; An investigation into causative factors in patients with bronchiectasis. Am J Respir Crit Care Med162:1277–1284 [CrossRef][PubMed]
    [Google Scholar]
  55. Penesyan A., Kumar S. S., Kamath K., Shathili A. M., Venkatakrishnan V., Krisp C., Packer N. H., Molloy M. P., Paulsen I. T.. 2015; Genetically and phenotypically distinct P seudomonas aeruginosa cystic fibrosis isolates share a core proteomic signature. PLoS One10:e0138527 [CrossRef][PubMed]
    [Google Scholar]
  56. Perez L. R., Machado A. B., Barth A. L.. 2013; The presence of quorum-sensing genes in Pseudomonas isolates infecting cystic fibrosis and non-cystic fibrosis patients. Curr Microbiol66:418–420 [CrossRef][PubMed]
    [Google Scholar]
  57. Puchelle E., Bajolet O., Abély M.. 2002; Airway mucus in cystic fibrosis. Paediatr Respir Rev3:115–119 [CrossRef][PubMed]
    [Google Scholar]
  58. Pujana I., Gallego L., Martín G., López F., Canduela J., Cisterna R.. 1999; Epidemiological analysis of sequential Pseudomonas aeruginosa isolates from chronic bronchiectasis patients without cystic fibrosis. J Clin Microbiol37:2071–2073[PubMed]
    [Google Scholar]
  59. Reimmann C., Beyeler M., Latifi A., Winteler H., Foglino M., Lazdunski A., Haas D.. 1997; The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase. Mol Microbiol24:309–319 [CrossRef][PubMed]
    [Google Scholar]
  60. Rust L., Messing C. R., Iglewski B. H.. 1994; Elastase assays. Methods Enzymol235:554–562[PubMed][CrossRef]
    [Google Scholar]
  61. Rust L., Pesci E. C., Iglewski B. H.. 1996; Analysis of the Pseudomonas aeruginosa elastase (lasB) regulatory region. J Bacteriol178:1134–1140 [CrossRef][PubMed]
    [Google Scholar]
  62. Saldanha A. J.. 2004; Java Treeview – extensible visualization of microarray data. Bioinformatics20:3246–3248 [CrossRef][PubMed]
    [Google Scholar]
  63. Sandoz K. M., Mitzimberg S. M., Schuster M.. 2007; Social cheating in Pseudomonas aeruginosa quorum sensing. Proc Natl Acad Sci USA104:15876–15881 [CrossRef][PubMed]
    [Google Scholar]
  64. Seitz A. E., Olivier K. N., Steiner C. A., Montes de Oca R., Holland S. M., Prevots D. R.. 2010; Trends and burden of bronchiectasis-associated hospitalizations in the United States, 1993-2006. Chest138:944–949 [CrossRef][PubMed]
    [Google Scholar]
  65. Seitz A. E., Olivier K. N., Adjemian J., Holland S. M., Prevots R.. 2012; Trends in bronchiectasis among Medicare beneficiaries in the United States, 2000 to 2007. Chest142:432–439 [CrossRef][PubMed]
    [Google Scholar]
  66. Shen K., Sayeed S., Antalis P., Gladitz J., Ahmed A., Dice B., Janto B., Dopico R., Keefe R. et al. 2006; Extensive genomic plasticity in Pseudomonas aeruginosa revealed by identification and distribution studies of novel genes among clinical isolates. Infect Immun74:5272–5283 [CrossRef][PubMed]
    [Google Scholar]
  67. Singh P. K., Schaefer A. L., Parsek M. R., Moninger T. O., Welsh M. J., Greenberg E. P.. 2000; Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature407:762–764 [CrossRef][PubMed]
    [Google Scholar]
  68. Smith E. E., Buckley D. G., Wu Z., Saenphimmachak C., Hoffman L. R., D'Argenio D. A., Miller S. I., Ramsey B. W., Speert D. P. et al. 2006; Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci USA103:8487–8492 [CrossRef][PubMed]
    [Google Scholar]
  69. Sokol P. A., Ohman D. E., Iglewski B. H.. 1979; A more sensitive plate assay for detection of protease production by Pseudomonas aeruginosa. J Clin Microbiol9:538–540[PubMed]
    [Google Scholar]
  70. Sousa A. M., Pereira M. O.. 2014; Pseudomonas aeruginosa diversification during infection development in cystic fibrosis lungs – a review. Pathogens3:680–703 [CrossRef][PubMed]
    [Google Scholar]
  71. Tingpej P., Smith L., Rose B., Zhu H., Conibear T., Al Nassafi K., Manos J., Elkins M., Bye P. et al. 2007; Phenotypic characterization of clonal and nonclonal Pseudomonas aeruginosa strains isolated from lungs of adults with cystic fibrosis. J Clin Microbiol45:1697–1704 [CrossRef][PubMed]
    [Google Scholar]
  72. Varga J. J., Barbier M., Mulet X., Bielecki P., Bartell J. A., Owings J. P., Martinez-Ramos I., Hittle L. E., Davis M. R. et al. 2015; Genotypic and phenotypic analyses of a Pseudomonas aeruginosa chronic bronchiectasis isolate reveal differences from cystic fibrosis and laboratory strains. BMC Genomics16:883 [CrossRef][PubMed]
    [Google Scholar]
  73. Weycker D., Edelsberg J., Oster G., Tino G.. 2005; Prevalence and economic burden of bronchiectasis. Clin Pulm Med12:205–209 [CrossRef]
    [Google Scholar]
  74. Workentine M. L., Sibley C. D., Glezerson B., Purighalla S., Norgaard-Gron J. C., Parkins M. D., Rabin H. R., Surette M. G.. 2013; Phenotypic heterogeneity of Pseudomonas aeruginosa populations in a cystic fibrosis patient. PLoS One8:e60225 [CrossRef][PubMed]
    [Google Scholar]
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