1887

Microbiology Society logo

Volume 162, Issue 12

Virulence adaptations of isolated from patients with non-cystic fibrosis bronchiectasis Open Access

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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): cystic fibrosis , non-cystic fibrosis bronchiectasis , phenotyping , Pseudomonas aeruginosa and virulence factors
© 2016 The Authors
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.000393
2016-12-21
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/micro/162/12/2126.html?itemId=/content/journal/micro/10.1099/mic.0.000393&mimeType=html&fmt=ahah

References

  1. Al-Shirawi N., Al-Jahdall H., Al Shimemeri A. 2006; Pathogenesis, etiology and treatment of bronchiectasis. Ann Thorac Med 1:41–51 [CrossRef]
     [Google Scholar]
  2. Barker A. F., Bardana E. J. 1988; Bronchiectasis: update of an orphan disease. Am Rev Respir Dis 137:969–978 [View Article][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 Med 2:738–749 [View Article][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 Microbiol 45:110–119 [View Article][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 Res 6:1–11 [View Article][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 Microbiol 37:1771–1776[PubMed]
     [Google Scholar]
  7. Chalmers J. D., Hill A. T. 2013; Mechanisms of immune dysfunction and bacterial persistence in non-cystic fibrosis bronchiectasis. Mol Immunol 55:27–34 [View Article][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 Rep 5:10932 [View Article][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. Microbiology 149:2291–2299 [View Article][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 Microbiol 64:512–533 [View Article][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 Bacteriol 183:1195–1204 [View Article][PubMed]
     [Google Scholar]
  13. Drake D., Montie T. C. 1988; Flagella, motility and invasive virulence of Pseudomonas aeruginosa . J Gen Microbiol 134:43–52 [View Article][PubMed]
     [Google Scholar]
  14. Drenkard E., Ausubel F. M. 2002; Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Nature 416:740–743 [View Article][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 Pharmacother 39:39–44 [View Article][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 One 10:e0143466 [View Article]
     [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 Pulmonol 34:91–100 [View Article][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 J 9:1601–1604 [View Article][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 Chemother 55:921–927 [View Article][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 Bacteriol 173:3000–3009 [View Article][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 Immun 80:3122–3131 [View Article][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 Chemother 63:728–732 [View Article][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 J 5:477–487[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 Res 13:21 [View Article][PubMed]
     [Google Scholar]
  25. Gupta A. K., Lodha R., Kabra S. K. 2015; Non cystic fibrosis bronchiectasis. Indian J Pediatr 82:938–944 [View Article][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. Microbiology 159:2354–2363 [View Article][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 Bacteriol 187:4875–4883 [View Article][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. Chest 114:1594–1598 [View Article][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 Fibros 8:66–70 [View Article][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 Immunol 358:91–118 [View Article][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. Microbiology 154:1584–1598 [View Article][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 Pediatr 116:714–719 [View Article][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 Med 100:2183–2189 [View Article][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 Med 101:1633–1638 [View Article][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 Bacteriol 182:5990–5996 [View Article][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 Pulmonol 32:277–287 [View Article][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 One 6:e27091 [View Article][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 Adv 1:e1500199 [View Article][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. JAMA 293:581–588 [View Article][PubMed]
     [Google Scholar]
  40. Lonon M. K., Woods D. E., Straus D. C. 1988; Production of lipase by clinical isolates Pseudomonas cepacia . J Clinic Microbiol 26:979–984
     [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 One 7:e35648 [View Article]
     [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. Microbiology 153:225–237 [View Article][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. Nature 426:306–310 [View Article][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 Physiol 301:L236–L246 [View Article][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 USA 105:3100–3105 [View Article][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. Chest 142:159–167 [View Article][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 Biol 24:621–626 [View Article][PubMed]
     [Google Scholar]
  48. Murray T. S., Kazmierczak B. I. 2006; FlhF is required for swimming and swarming in Pseudomonas aeruginosa . J Bacteriol 188:6995–7004 [View Article][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 Res 15:21 [View Article][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. Chest 113:1329–1334[PubMed] [CrossRef]
     [Google Scholar]
  51. O'Toole G. A., Kolter R. 1998; Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol Microbiol 30:295–304 [View Article][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. Science 288:1251–1254 [View Article][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 Microbiol 52:1127–1135 [View Article][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 Med 162:1277–1284 [View Article][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 One 10:e0138527 [View Article][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 Microbiol 66:418–420 [View Article][PubMed]
     [Google Scholar]
  57. Puchelle E., Bajolet O., Abély M. 2002; Airway mucus in cystic fibrosis. Paediatr Respir Rev 3:115–119 [View Article][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 Microbiol 37:2071–2073[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 Microbiol 24:309–319 [View Article][PubMed]
     [Google Scholar]
  60. Rust L., Messing C. R., Iglewski B. H. 1994; Elastase assays. Methods Enzymol 235:554–562[PubMed] [CrossRef]
     [Google Scholar]
  61. Rust L., Pesci E. C., Iglewski B. H. 1996; Analysis of the Pseudomonas aeruginosa elastase (lasB) regulatory region. J Bacteriol 178:1134–1140 [View Article][PubMed]
     [Google Scholar]
  62. Saldanha A. J. 2004; Java Treeview – extensible visualization of microarray data. Bioinformatics 20:3246–3248 [View Article][PubMed]
     [Google Scholar]
  63. Sandoz K. M., Mitzimberg S. M., Schuster M. 2007; Social cheating in Pseudomonas aeruginosa quorum sensing. Proc Natl Acad Sci USA 104:15876–15881 [View Article][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. Chest 138:944–949 [View Article][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. Chest 142:432–439 [View Article][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 Immun 74:5272–5283 [View Article][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. Nature 407:762–764 [View Article][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 USA 103:8487–8492 [View Article][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 Microbiol 9:538–540[PubMed]
     [Google Scholar]
  70. Sousa A. M., Pereira M. O. 2014; Pseudomonas aeruginosa diversification during infection development in cystic fibrosis lungs – a review. Pathogens 3:680–703 [View Article][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 Microbiol 45:1697–1704 [View Article][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 Genomics 16:883 [View Article][PubMed]
     [Google Scholar]
  73. Weycker D., Edelsberg J., Oster G., Tino G. 2005; Prevalence and economic burden of bronchiectasis. Clin Pulm Med 12:205–209 [View Article]
     [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 One 8:e60225 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.000393
Loading
Virulence adaptations of Pseudomonas aeruginosa isolated from patients with non-cystic fibrosis bronchiectasis
Microbiology 162, 2126 (2016); https://doi.org/10.1099/mic.0.000393
/content/journal/micro/10.1099/mic.0.000393
/content/journal/micro/10.1099/mic.0.000393
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error