1887

Abstract

is the pathogen most commonly associated with morbidity and mortality in cystic fibrosis (CF) patients. The host–pathogen interactions responsible for progressive CF lung diseases are complex. However, there is growing interest in the role of hypermutable (that is, those strains with an increased mutation frequency due to mutations in mismatch repair and error prevention genes), in terms of both bacterial adaptation and antimicrobial resistance. The prevalence of hypermutable in chronic CF infection has been established, and at 37 % is surprisingly high. To the authors’ knowledge, there are no reports of prevalence during the early stages of infection, in environmental pseudomonas, which are believed to be the primary source of infection, and in epidemic strains, which have emerged as a major challenge. The aim of this study was to establish the prevalence of hypermutable in these pseudomonas populations. The hypothesis was that hypermutability would be rare in early and in environmental but in contrast would explain the relatively recent emergence of epidemic strains. It was found that 10/100 (10 %) of early isolates were strong or weak mutators, suggesting that the CF lung is not the only factor influencing the existence of mutators in this group of patients. Two weak mutators (6 %) were found in 32 environmental isolates. Only two of 15 (13 %) epidemic strains were hypermutable, and although closer analysis revealed this issue to be complex, on the whole the data suggested that the atypical characteristics of these highly transmissible strains cannot solely be explained by this phenomenon. The higher than predicted prevalence of mutators in early infection, and in environmental isolates, reinforces the importance of early and aggressive treatment for infection in CF.

Keyword(s): CF, cystic fibrosis
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.2006/005082-0
2007-06-01
2020-01-20
Loading full text...

Full text loading...

/deliver/fulltext/micro/153/6/1852.html?itemId=/content/journal/micro/10.1099/mic.0.2006/005082-0&mimeType=html&fmt=ahah

References

  1. Al-Aloul M., Miller H., Stockton P., Ledson M. J., Walshaw M. J.. 2005; Acute renal failure in CF patients chronically infected by the Liverpool epidemic Pseudomonas aeruginosa strain (LES. J Cyst Fibros4:197–201[CrossRef]
    [Google Scholar]
  2. Armstrong D. S., Nixon G. M., Carzino R., Bigham A., Carlin J. B., Robins-Browne R. M., Grimwood K.. 2002; Detection of a widespread clone of Pseudomonas aeruginosa in a pediatric cystic fibrosis clinic. Am J Respir Crit Care Med166:983–987[CrossRef]
    [Google Scholar]
  3. Armstrong D., Bell S., Robinson M., Bye P., Rose B., Harbour C., Lee C., Service H., Nissen M.. other authors 2003; Evidence for spread of a clonal strain of Pseudomonas aeruginosa among cystic fibrosis clinics. J Clin Microbiol41:2266–2267[CrossRef]
    [Google Scholar]
  4. Baquero M.-R., Nilsson A. I., Sandvang D., Frimodt-Møller N., Baquero F., Andersson D. I., del Carmen Turrientes M., Galán J. C., Martínez J. L.. 2004; Polymorphic mutation frequencies in Escherichia coli : emergence of weak mutators in clinical isolates. J Bacteriol186:5538–5542[CrossRef]
    [Google Scholar]
  5. Blazquez J.. 2003; Hypermutation as a factor contributing to the acquisition of antimicrobial resistance. Clin Infect Dis37:1201–1209[CrossRef]
    [Google Scholar]
  6. Burns J. L., Gibson R. L., McNamara S., Yim D., Emerson J., Rosenfeld M., Hiatt P., McCoy K., Castile R.. other authors 2001; Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis. J Infect Dis183:444–452[CrossRef]
    [Google Scholar]
  7. Butler S. L., Doherty C. J., Hughes J. E., Nelson J. W., Govan J. R. W.. 1995; Burkholderia cepacia and cystic fibrosis: do natural environments present a potential hazard?. J Clin Microbiol33:1001–1004
    [Google Scholar]
  8. Chambers D., Scott F., Bangur R., Davies R., Lim A., Walters S., Smith G., Pitt T., Stableforth D., Honeybourne D.. 2005; Factors associated with infection by Pseudomonas aeruginosa in adult cystic fibrosis. Eur Respir J26:651–656[CrossRef]
    [Google Scholar]
  9. Chao L., Cox E. C.. 1983; Competition between high and low mutating strains of Escherichia coli.. Evolution37:125–134[CrossRef]
    [Google Scholar]
  10. Cheng K., Smyth R. L., Govan J. R. W., Doherty C., Winstanley C., Denning N., Heaf D. P., Hart C. A., van Saene H.. 1996; Spread of a β -lactam-resistant Pseudomonas aeruginosa in a cystic fibrosis clinic. Lancet348:639–642[CrossRef]
    [Google Scholar]
  11. Ciofu O., Riis B., Pressler T., Poulsen H. E., Hoiby N.. 2005; Occurrence of hypermutable Pseudomonas aeruginosa in cystic fibrosis patients is associated with the oxidative stress caused by chronic lung inflammation. Antimicrob Agents Chemother49:2276–2282[CrossRef]
    [Google Scholar]
  12. Curran B., Morgan J. A. W., Honeybourne D., Dowson C. G.. 2005; Commercial mushrooms and bean sprouts are a source of Pseudomonas aeruginosa.. J Clin Microbiol43:5830–5831[CrossRef]
    [Google Scholar]
  13. Edenborough F. P., Stone H. R., Kelly S. J., Zadik P., Doherty C. J., Govan J. R. W.. 2004; Genotyping of Pseudomonas aeruginosa in cystic fibrosis suggests need for segregation. J Cyst Fibros3:37–44
    [Google Scholar]
  14. Gibson R. L., Burns J. L., Ramsey B. W.. 2003; Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med168:918–951[CrossRef]
    [Google Scholar]
  15. Goldberg J. B.. 2000; Pseudomonas : global bacteria. Trends Microbiol8:55–57[CrossRef]
    [Google Scholar]
  16. Gutiérrez O., Juan C., Oliver A., Pérez J. L.. 2004; Lack of association between hypermutation and antibiotic resistance development in Pseudomonas aeruginosa isolates from intensive care unit patients. Antimicrob Agents Chemother48:3573–3575[CrossRef]
    [Google Scholar]
  17. Hall L. M. C., Henderson-Begg S. K.. 2006; Hypermutable bacteria isolated from humans – a critical analysis. Microbiology152:2505–2514[CrossRef]
    [Google Scholar]
  18. Herman G. E., Modrich P.. 1981; Escherichia coli K12 clones that overproduce dam methylase are hypermutable. J Bacteriol145:644–646
    [Google Scholar]
  19. Hogardt M., Schubert S., Adler K., Heesemann J., Götzfried M.. 2006; Sequence variability and functional analysis of MutS of hypermutable Pseudomonas aeruginosa cystic fibrosis isolates. Int J Med Microbiol296:313–320[CrossRef]
    [Google Scholar]
  20. Jones A. M., Govan J. R. W., Doherty C. J., Dodd M. E., Isalska B. J., Stanbridge N., Webb A. K.. 2001; Spread of a multi-resistant strain of Pseudomonas aeruginosa in an adult cystic fibrosis clinic. Lancet358:557–558[CrossRef]
    [Google Scholar]
  21. Jones A. M., Govan J. R. W., Doherty C. J., Dodd M. E., Isalska B. J., Stanbridge N., Webb A. K.. 2003; Identification of airborne dissemination of epidemic multiresistant strains of Pseudomonas aeruginosa at a CF centre during a cross-infection outbreak. Thorax58:525–527[CrossRef]
    [Google Scholar]
  22. Kelly N. M., Falkiner F. R., Keane C. T.. 1983; Acetamide broth for isolation of Pseudomonas aeruginosa from patients with cystic fibrosis. J Clin Microbiol17:159
    [Google Scholar]
  23. Maciá M. D., Borrell N., Oliver A., Pérez J. L.. 2004; Detection and susceptibility testing of hypermutable Pseudomonas aeruginosa with the Etest and disk diffusion. Antimicrob Agents Chemother48:2665–2672[CrossRef]
    [Google Scholar]
  24. Maciá M. D., Blanquer D., Togores B., Sauleda J., Oliver A., Pérez J. L.. 2005; Hypermutation is a key factor in development of multiple-antimicrobial resistance in Pseudomonas aeruginosa strains causing chronic lung infections. Antimicrob Agents Chemother49:3382–3386[CrossRef]
    [Google Scholar]
  25. Maciá M. D., Borrell N., Segura M., Oliver A., Gómez C., Pérez J. L.. 2006; Efficacy and potential for resistance selection of antipseudomonal treatments in a mouse model of lung infection by hypermutable Pseudomonas aeruginosa. Antimicrob Agents Chemother50:975–983[CrossRef]
    [Google Scholar]
  26. McCallum S. J., Corkhill J., Gallagher M., Ledson M. J., Hart C. A., Walshaw M. J.. 2001; Superinfection with a transmissible strain of Pseudomonas aeruginosa in adults with cystic fibrosis chronically colonised by P. aeruginosa. Lancet358:558–560[CrossRef]
    [Google Scholar]
  27. Obmolova G., Ban C., Hsieh P., Yang W.. 2000; Crystal structure of mismatch repair protein MutS and its complex with a substrate DNA. Nature407:703–710[CrossRef]
    [Google Scholar]
  28. Oliver A., Canton R., Campo P., Baquero F., Blazquez J.. 2000; High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science288:1251–1253[CrossRef]
    [Google Scholar]
  29. Oliver A., Baquero F., Blázquez J.. 2002; The mismatch repair system ( mutS, mutL and uvrD genes) in Pseudomonas aeruginosa : molecular characterisation of naturally occurring mutants. Mol Microbiol43:1641–1650[CrossRef]
    [Google Scholar]
  30. Oliver A., Levin B. R., Juan C., Baquero F., Blazquez J.. 2004; Hypermutation and the preexistence of antibiotic-resistant Pseudomonas aeruginosa mutants: implications for susceptibility testing and treatment of chronic infections. Antimicrob Agents Chemother48:4226–4233[CrossRef]
    [Google Scholar]
  31. Panagea S., Winstanley C., Walshaw M. J., Ledson M. J., Hart C. A.. 2005; Environmental contamination with an epidemic strain of Pseudomonas aeruginosa in a Liverpool cystic fibrosis centre, and a study of its survival on dry surfaces. J Hosp Infect59:102–107[CrossRef]
    [Google Scholar]
  32. Prunier A. L., Malbruny B., Laurans M., Brouard J., Duhamel J. F., Leclercq R.. 2003; High rate of macrolide resistance in Staphylococcus aureus strains from patients with cystic fibrosis reveals high proportions of hypermutable strains. J Infect Dis187:1709–1716[CrossRef]
    [Google Scholar]
  33. Román F., Canton R., Perez-Vazquez M., Baquero F., Campos J.. 2004; Dynamics of long-term colonisation of respiratory tract by Haemophilus influenzae in cystic fibrosis patients shows a marked increase in hypermutable strains. J Clin Microbiol42:1450–1459[CrossRef]
    [Google Scholar]
  34. Römling U., Wingender J., Müller H., Tümmler B.. 1994; A major cystic fibrosis clone common to patients and aquatic habitats. Appl Environ Microbiol60:1734–1738
    [Google Scholar]
  35. Rosche W. A., Foster P. L.. 1999; The role of transient hypermutators in adaptive mutation in Escherichia coli. Proc Natl Acad Sci U S A96:6862–6867[CrossRef]
    [Google Scholar]
  36. Salunkhe P., Smart C. H., Morgan J. A., Panagea S., Walshaw M. J., Hart C. A., Geffers R., Tummler B., Winstanley C.. 2005; A cystic fibrosis epidemic strain of Pseudomonas aeruginosa displays enhanced virulence and antimicrobial resistance. J Bacteriol187:4908–4920[CrossRef]
    [Google Scholar]
  37. Scott F. W., Pitt T. L.. 2004; Identification and characterisation of transmissible Pseudomonas aeruginosa strains in cystic fibrosis patients in England and Wales. J Med Microbiol53:609–615[CrossRef]
    [Google Scholar]
  38. Smith E. E., Buckley D. G., Wu Z., Saeniphimmachak C., Hoffman L. R., D’Argenio D. A., Miller S. I., Ramsey B. W., Speert D. P.. other authors 2006; Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci U S A103:8487–8492[CrossRef]
    [Google Scholar]
  39. Spilker T., Coeyne T., Vandamme P., LiPuma J. J.. 2004; PCR-based assay for the differentiation of Pseudomonas aeruginosa from other species of Pseudomonas recovered from cystic fibrosis patients. J Clin Microbiol42:2074–2079[CrossRef]
    [Google Scholar]
  40. Taylor R. F., Morgan D. W., Nicholson P. S., Mackay I. S., Hodson M. E., Pitt T. L.. 1992; Extrapulmonary sites of Pseudomonas aeruginosa in adults with cystic fibrosis. Thorax47:426–428[CrossRef]
    [Google Scholar]
  41. Watson M. E. Jr, Burns J. L., Smith A. L.. 2004; Hypermutable Haemophilus influenzae with mutations in mutS are found in cystic fibrosis sputum. Microbiology150:2947–2958[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.2006/005082-0
Loading
/content/journal/micro/10.1099/mic.0.2006/005082-0
Loading

Data & Media loading...

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