1887

Abstract

Hypermutable bacteria of several species have been described among isolates recovered from humans over the last decade. Interpretation of the literature in this area is complicated by diversity in the determination and definition of hypermutability, and this review outlines the different methods used. Inactivation of the mismatch repair gene is often implicated in the mutator phenotype; the reported effect of inactivation on mutation frequency varies widely between species, from under 10-fold to nearly 1000-fold, but also varies among different reports on the same species. Particularly high proportions of mutators have been reported among and other species in the cystic fibrosis lung, epidemic serogroup A , and . Aspects of the biology of these infections that could be relevant to hypermutability are discussed, and some future directions that may increase our understanding of mutators among bacteria isolated from humans are considered.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.29079-0
2006-09-01
2019-10-17
Loading full text...

Full text loading...

/deliver/fulltext/micro/152/9/2505.html?itemId=/content/journal/micro/10.1099/mic.0.29079-0&mimeType=html&fmt=ahah

References

  1. Baquero, M. R., Nilsson, A. I., Turrientes Mdel, C., Sandvang, D., Galan, J. C., Martinez, J. L., Frimodt-Moller, N., Baquero, F. & Andersson, D. I. ( 2004; ). Polymorphic mutation frequencies in Escherichia coli: emergence of weak mutators in clinical isolates. J Bacteriol 186, 5538–5542.[CrossRef]
    [Google Scholar]
  2. Baquero, M. R., Galan, J. C., del Carmen Turrientes, M., Canton, R., Coque, T. M., Martinez, J. L. & Baquero, F. ( 2005; ). Increased mutation frequencies in Escherichia coli isolates harboring extended-spectrum beta-lactamases. Antimicrob Agents Chemother 49, 4754–4756.[CrossRef]
    [Google Scholar]
  3. Bjedov, I., Tenaillon, O., Gerard, B., Souza, V., Denamur, E., Radman, M., Taddei, F. & Matic, I. ( 2003; ). Stress-induced mutagenesis in bacteria. Science 300, 1404–1409.[CrossRef]
    [Google Scholar]
  4. Bjorkholm, B., Sjolund, M., Falk, P. G., Berg, O. G., Engstrand, L. & Andersson, D. I. ( 2001; ). Mutation frequency and biological cost of antibiotic resistance in Helicobacter pylori. Proc Natl Acad Sci U S A 98, 14607–14612.[CrossRef]
    [Google Scholar]
  5. Blazquez, J. ( 2003; ). Hypermutation as a factor contributing to the acquisition of antimicrobial resistance. Clin Infect Dis 37, 1201–1209.[CrossRef]
    [Google Scholar]
  6. Blazquez, J., Oliver, A. & Gomez-Gomez, J. M. ( 2002; ). Mutation and evolution of antibiotic resistance: antibiotics as promoters of antibiotic resistance? Curr Drug Targets 3, 345–349.[CrossRef]
    [Google Scholar]
  7. Bridges, B. A. ( 2001; ). Hypermutation in bacteria and other cellular systems. Philos Trans R Soc Lond B Biol Sci 356, 29–39.[CrossRef]
    [Google Scholar]
  8. Bucci, C., Lavitola, A., Salvatore, P., Del Giudice, L., Massardo, D. R., Bruni, C. B. & Alifano, P. ( 1999; ). Hypermutation in pathogenic bacteria: frequent phase variation in meningococci is a phenotypic trait of a specialized mutator biotype. Mol Cell 3, 435–445.[CrossRef]
    [Google Scholar]
  9. Chopra, I., O'Neill, A. J. & Miller, K. ( 2003; ). The role of mutators in the emergence of antibiotic-resistant bacteria. Drug Resist Updat 6, 137–145.[CrossRef]
    [Google Scholar]
  10. 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 Chemother 49, 2276–2282.[CrossRef]
    [Google Scholar]
  11. Crane, G. J., Thomas, S. M. & Jones, M. E. ( 1996; ). A modified Luria-Delbruck fluctuation assay for estimating and comparing mutation rates. Mutat Res 354, 171–182.[CrossRef]
    [Google Scholar]
  12. Davidsen, T., Bjoras, M., Seeberg, E. C. & Tonjum, T. ( 2005; ). Antimutator role of DNA glycosylase MutY in pathogenic Neisseria species. J Bacteriol 187, 2801–2809.[CrossRef]
    [Google Scholar]
  13. del Campo, R., Morosini, M. I., de la Pedrosa, E. G., Fenoll, A., Munoz-Almagro, C., Maiz, L., Baquero, F. & Canton, R. ( 2005; ). Population structure, antimicrobial resistance, and mutation frequencies of Streptococcus pneumoniae isolates from cystic fibrosis patients. J Clin Microbiol 43, 2207–2214.[CrossRef]
    [Google Scholar]
  14. Denamur, E., Bonacorsi, S., Giraud, A. & 8 other authors ( 2002; ). High frequency of mutator strains among human uropathogenic Escherichia coli isolates. J Bacteriol 184, 605–609.[CrossRef]
    [Google Scholar]
  15. Drake, J. W. ( 1991; ). A constant rate of spontaneous mutation in DNA-based microbes. Proc Natl Acad Sci U S A 88, 7160–7164.[CrossRef]
    [Google Scholar]
  16. Foster, P. L. ( 2005; ). Stress responses and genetic variation in bacteria. Mutat Res 569, 3–11.[CrossRef]
    [Google Scholar]
  17. Garibyan, L., Huang, T., Kim, M. & 8 other authors ( 2003; ). Use of the rpoB gene to determine the specificity of base substitution mutations on the Escherichia coli chromosome. DNA Repair 2, 593–608.[CrossRef]
    [Google Scholar]
  18. Gillespie, S. H., Basu, S., Dickens, A. L., O'Sullivan, D. M. & McHugh, T. D. ( 2005; ). Effect of subinhibitory concentrations of ciprofloxacin on Mycobacterium fortuitum mutation rates. J Antimicrob Chemother 56, 344–348.[CrossRef]
    [Google Scholar]
  19. Giraud, A., Matic, I., Tenaillon, O., Clara, A., Radman, M., Fons, M. & Taddei, F. ( 2001; ). Costs and benefits of high mutation rates: adaptive evolution of bacteria in the mouse gut. Science 291, 2606–2608.[CrossRef]
    [Google Scholar]
  20. Gutierrez, O., Juan, C., Perez, J. L. & Oliver, A. ( 2004; ). Lack of association between hypermutation and antibiotic resistance development in Pseudomonas aeruginosa isolates from intensive care unit patients. Antimicrob Agents Chemother 48, 3573–3575.[CrossRef]
    [Google Scholar]
  21. Henderson-Begg, S. K., Livermore, D. M. & Hall, L. M. ( 2006; ). Effect of subinhibitory concentrations of antibiotics on mutation frequency in Streptococcus pneumoniae. J Antimicrob Chemother 57, 849–854.[CrossRef]
    [Google Scholar]
  22. Kim, M., Huang, T. & Miller, J. H. ( 2003; ). Competition between MutY and mismatch repair at A×C mispairs in vivo. J Bacteriol 185, 4626–4629.[CrossRef]
    [Google Scholar]
  23. LeClerc, J. E., Li, B., Payne, W. L. & Cebula, T. A. ( 1996; ). High mutation frequencies among Escherichia coli and Salmonella pathogens. Science 274, 1208–1211.[CrossRef]
    [Google Scholar]
  24. Li, B., Tsui, H. C., LeClerc, J. E., Dey, M., Winkler, M. E. & Cebula, T. A. ( 2003; ). Molecular analysis of mutS expression and mutation in natural isolates of pathogenic Escherichia coli. Microbiology 149, 1323–1331.[CrossRef]
    [Google Scholar]
  25. Luria, S. E. & Delbrück, M. ( 1943; ). Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28, 491–511.
    [Google Scholar]
  26. Macia, M. D., Blanquer, D., Togores, B., Sauleda, J., Perez, J. L. & Oliver, A. ( 2005; ). Hypermutation is a key factor in development of multiple-antimicrobial resistance in Pseudomonas aeruginosa strains causing chronic lung infections. Antimicrob Agents Chemother 49, 3382–3386.[CrossRef]
    [Google Scholar]
  27. Mao, E. F., Lane, L., Lee, J. & Miller, J. H. ( 1997; ). Proliferation of mutators in a cell population. J Bacteriol 179, 417–422.
    [Google Scholar]
  28. Martin, P., Sun, L., Hood, D. W. & Moxon, E. R. ( 2004; ). Involvement of genes of genome maintenance in the regulation of phase variation frequencies in Neisseria meningitidis. Microbiology 150, 3001–3012.[CrossRef]
    [Google Scholar]
  29. Miller, K., O'Neill, A. J. & Chopra, I. ( 2002; ). Response of Escherichia coli hypermutators to selection pressure with antimicrobial agents from different classes. J Antimicrob Chemother 49, 925–934.[CrossRef]
    [Google Scholar]
  30. Morosini, M. I., Baquero, M. R., Sanchez-Romero, J. M., Negri, M. C., Galan, J. C., del Campo, R., Perez-Diaz, J. C. & Baquero, F. ( 2003; ). Frequency of mutation to rifampin resistance in Streptococcus pneumoniae clinical strains: hexA and hexB polymorphisms do not account for hypermutation. Antimicrob Agents Chemother 47, 1464–1467.[CrossRef]
    [Google Scholar]
  31. Notley-McRobb, L., Pinto, R., Seeto, S. & Ferenci, T. ( 2002a; ). Regulation of mutY and nature of mutator mutations in Escherichia coli populations under nutrient limitation. J Bacteriol 184, 739–745.[CrossRef]
    [Google Scholar]
  32. Notley-McRobb, L., Seeto, S. & Ferenci, T. ( 2002b; ). Enrichment and elimination of mutY mutators in Escherichia coli populations. Genetics 162, 1055–1062.
    [Google Scholar]
  33. Oliver, A., Canton, R., Campo, P., Baquero, F. & Blazquez, J. ( 2000; ). High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288, 1251–1254.[CrossRef]
    [Google Scholar]
  34. Oliver, A., Baquero, F. & Blazquez, J. ( 2002a; ). The mismatch repair system (mutS, mutL and uvrD genes) in Pseudomonas aeruginosa: molecular characterization of naturally occurring mutants. Mol Microbiol 43, 1641–1650.[CrossRef]
    [Google Scholar]
  35. Oliver, A., Sanchez, J. M. & Blazquez, J. ( 2002b; ). Characterization of the GO system of Pseudomonas aeruginosa. FEMS Microbiol Lett 217, 31–35.[CrossRef]
    [Google Scholar]
  36. O'Neill, A. J. & Chopra, I. ( 2002; ). Insertional inactivation of mutS in Staphylococcus aureus reveals potential for elevated mutation frequencies, although the prevalence of mutators in clinical isolates is low. J Antimicrob Chemother 50, 161–169.[CrossRef]
    [Google Scholar]
  37. Pang, P. P., Lundberg, A. S. & Walker, G. C. ( 1985; ). Identification and characterization of the mutL and mutS gene products of Salmonella typhimurium LT2. J Bacteriol 163, 1007–1015.
    [Google Scholar]
  38. Perez-Capilla, T., Baquero, M. R., Gomez-Gomez, J. M., Ionel, A., Martin, S. & Blazquez, J. ( 2005; ). SOS-independent induction of dinB transcription by beta-lactam-mediated inhibition of cell wall synthesis in Escherichia coli. J Bacteriol 187, 1515–1518.[CrossRef]
    [Google Scholar]
  39. Prunier, A. L. & Leclercq, R. ( 2005; ). Role of mutS and mutL genes in hypermutability and recombination in Staphylococcus aureus. J Bacteriol 187, 3455–3464.[CrossRef]
    [Google Scholar]
  40. 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 Dis 187, 1709–1716.[CrossRef]
    [Google Scholar]
  41. Richardson, A. R. & Stojiljkovic, I. ( 2001; ). Mismatch repair and the regulation of phase variation in Neisseria meningitidis. Mol Microbiol 40, 645–655.[CrossRef]
    [Google Scholar]
  42. Richardson, A. R., Yu, Z., Popovic, T. & Stojiljkovic, I. ( 2002; ). Mutator clones of Neisseria meningitidis in epidemic serogroup A disease. Proc Natl Acad Sci U S A 99, 6103–6107.[CrossRef]
    [Google Scholar]
  43. Rosche, W. A. & Foster, P. L. ( 2000; ). Determining mutation rates in bacterial populations. Methods 20, 4–17.[CrossRef]
    [Google Scholar]
  44. Rosenberg, S. M., Thulin, C. & Harris, R. S. ( 1998; ). Transient and heritable mutators in adaptive evolution in the lab and in nature. Genetics 148, 1559–1566.
    [Google Scholar]
  45. Samrakandi, M. M. & Pasta, F. ( 2000; ). Hyperrecombination in Streptococcus pneumoniae depends on an atypical mutY homologue. J Bacteriol 182, 3353–3360.[CrossRef]
    [Google Scholar]
  46. Shaver, A. C., Dombrowski, P. G., Sweeney, J. Y., Treis, T., Zappala, R. M. & Sniegowski, P. D. ( 2002; ). Fitness evolution and the rise of mutator alleles in experimental Escherichia coli populations. Genetics 162, 557–566.
    [Google Scholar]
  47. Sniegowski, P. D., Gerrish, P. J. & Lenski, R. E. ( 1997; ). Evolution of high mutation rates in experimental populations of E. coli. Nature 387, 703–705.[CrossRef]
    [Google Scholar]
  48. Sniegowski, P. D., Gerrish, P. J., Johnson, T. & Shaver, A. ( 2000; ). The evolution of mutation rates: separating causes from consequences. Bioessays 22, 1057–1066.[CrossRef]
    [Google Scholar]
  49. Tatusov, R. L., Fedorova, N. D., Jackson, J. D. & 14 other authors ( 2003; ). The COG database: an updated version includes eukaryotes. BMC Bioinformatics 4, 41.[CrossRef]
    [Google Scholar]
  50. Thomas, S. R., Ray, A., Hodson, M. E. & Pitt, T. L. ( 2000; ). Increased sputum amino acid concentrations and auxotrophy of Pseudomonas aeruginosa in severe cystic fibrosis lung disease. Thorax 55, 795–797.[CrossRef]
    [Google Scholar]
  51. Trong, H. N., Prunier, A. L. & Leclercq, R. ( 2005; ). Hypermutable and fluoroquinolone-resistant clinical isolates of Staphylococcus aureus. Antimicrob Agents Chemother 49, 2098–2101.[CrossRef]
    [Google Scholar]
  52. Watson, M. E., Jr, Burns, J. L. & Smith, A. L. ( 2004; ). Hypermutable Haemophilus influenzae with mutations in mutS are found in cystic fibrosis sputum. Microbiology 150, 2947–2958.[CrossRef]
    [Google Scholar]
  53. Young, D. M. & Ornston, L. N. ( 2001; ). Functions of the mismatch repair gene mutS from Acinetobacter sp. strain ADP1. J Bacteriol 183, 6822–6831.[CrossRef]
    [Google Scholar]
  54. Zhao, J. & Winkler, M. E. ( 2000; ). Reduction of GC→TA transversion mutation by overexpression of MutS in Escherichia coli K-12. J Bacteriol 182, 5025–5028.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.29079-0
Loading
/content/journal/micro/10.1099/mic.0.29079-0
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