1887

Abstract

is one of the most important opportunistic pathogens involved in nosocomial infections, cystic fibrosis patients included. Hospital isolates frequently present multidrug-resistance (MDR) phenotypes as the consequence of constant antibiotic selective pressure. The kinetics of emergence of MDR mutants under antibiotic selective pressure indicated that long-term incubation in the presence of the bacteriostatic antibiotic tetracycline increases the mutation rate per cell per day of PAO1 by several orders of magnitude. The tetracycline-resistant mutants obtained were stable, showed decreased susceptibility to antibiotics belonging to different structural families, and contained an outer-membrane protein not present in the wild-type strain PAO1. These data are consistent with the hypothesis that incubation in the presence of tetracycline favours the emergence of MDR mutants in . The results are relevant for understanding the rapid emergence of antibiotic-resistant mutants among bacterial populations during infections. Their relationship to other models of increased mutagenesis under stress is discussed with respect to the adaptive mutation phenomenon.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-145-10-2857
1999-10-01
2021-10-20
Loading full text...

Full text loading...

/deliver/fulltext/micro/145/10/1452857a.html?itemId=/content/journal/micro/10.1099/00221287-145-10-2857&mimeType=html&fmt=ahah

References

  1. Atlas, R. M. (1993).Handbook of Microbiological Media. London: CRC Press.
  2. Baquero, F. & Blazquez, J. (1997). Evolution of antibiotic resistance. Trends Ecol Evol 12, 482-487.[CrossRef] [Google Scholar]
  3. Baquero, F., Negri, M. C., Morosini, M. I. & Blazquez, J. (1997). The antibiotic selective process: concentration-specific amplification of low-level resistant populations. Ciba Found Symp 207, 93-105. [Google Scholar]
  4. Bonhoeffer, S., Lipsitch, M. & Levin, B. R. (1997). Evaluating treatment protocols to prevent antibiotic resistance. Proc Natl Acad Sci USA 94, 12106-12111.[CrossRef] [Google Scholar]
  5. Cairns, J. & Foster, P. L. (1991). Adaptive reversion of a frameshift mutation in Escherichia coli. Genetics 128, 695-701. [Google Scholar]
  6. Clerch, B., Barbe, J. & Llagostera, M. (1992). The role of the excision and error-prone repair systems in mutagenesis by fluorinated quinolones in Salmonella typhimurium. Mutat Res 281, 207-213.[CrossRef] [Google Scholar]
  7. Deguchi, T., Kawamura, T., Yasuda, M., Nakano, M., Fukuda, H., Kato, H., Kato, N., Okano, Y. & Kawada, Y. (1997). In vivo selection of Klebsiella pneumoniae strains with enhanced quinolone resistance during fluoroquinolone treatment of urinary tract infections. Antimicrob Agents Chemother 41, 1609-1611. [Google Scholar]
  8. Everett, M. J., Jin, Y. F., Ricci, V. & Piddock, L. J. V. (1996). Contributions of individual mechanisms to fluoroquinolone resistance in 36 Escherichia coli strains isolated from humans and animals. Antimicrob Agents Chemother 40, 2380-2386. [Google Scholar]
  9. Fukuoka, T., Masuda, N., Takenouchi, T., Sekine, N., Iijima, M. & Ohya, S. (1991). Increase in susceptibility of Pseudomonas aeruginosa to carbapenem antibiotics in low-amino-acid media. Antimicrob Agents Chemother 35, 529-532.[CrossRef] [Google Scholar]
  10. Gottesman, M. M., Hrycyna, C. A., Schoenlein, P. V., Germann, U. A. & Pastan, I. (1995). Genetic analysis of the multidrug transporter. Annu Rev Genet 29, 607-649.[CrossRef] [Google Scholar]
  11. Govan, J. R. & Nelson, J. W. (1992). Microbiology of lung infection in cystic fibrosis. Br Med Bull 48, 912-930. [Google Scholar]
  12. Kanematsu, E., Deguchi, T., Yasuda, M., Kawamura, T., Nishino, Y. & Kawada, Y. (1998). Alterations in the GyrA subunit of DNA gyrase and the ParC subunit of DNA topoisomerase IV associated with quinolone resistance in Enterococcus faecalis. Antimicrob Agents Chemother 42, 433-435. [Google Scholar]
  13. Kasak, L., Horak, R. & Kivisaar, M. (1997). Promoter-creating mutations in Pseudomonas putida: a model system for the study of mutation in starving bacteria. Proc Natl Acad Sci USA 94, 3134-3139.[CrossRef] [Google Scholar]
  14. Kerem, B., Rommens, J. M., Buchanan, J. A., Markiewicz, D., Cox, T. K., Chakravarti, A., Buchwald, M. & Tsui, L. C. (1989). Identification of the cystic fibrosis gene: genetic analysis. Science 245, 1073-1080.[CrossRef] [Google Scholar]
  15. Köhler, T., Michea-Hamzehpour, M., Henze, U., Gotoh, N., Curty, L. K. & Pechère, J. C. (1997a). Characterization of MexE-MexF-OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa. Mol Microbiol 23, 345-354.[CrossRef] [Google Scholar]
  16. Köhler, T., Michea-Hamzehpour, M., Plesiat, P., Kahr, A. L. & Pechère, J. C. (1997b). Differential selection of multidrug efflux systems by quinolones in Pseudomonas aeruginosa. Antimicrob Agents Chemother 41, 2540-2543. [Google Scholar]
  17. McKenzie, G. J., Lombardo, M. J. & Rosenberg, S. M. (1998). Recombination-dependent mutation in Escherichia coli occurs in stationary phase. Genetics 149, 1163-1165. [Google Scholar]
  18. Maenhaut-Michel, G. & Shapiro, J. A. (1994). The roles of starvation and selective substrates in the emergence of araB-lacZ fusion clones. EMBO J 13, 5229-5239. [Google Scholar]
  19. Martı́nez, J. L., Alonso, A., Gómez-Gómez, J. M. & Baquero, F. (1998). Quinolone resistance by mutations in chromosomal gyrase genes. Just the tip of the iceberg? J Antimicrob Chemother 42, 683-688.[CrossRef] [Google Scholar]
  20. Mittler, J. E. & Lenski, R. E. (1990). New data on excisions of Mu from E. coli MCS2 cast doubt on directed mutation hypothesis. Nature 344, 173-175.[CrossRef] [Google Scholar]
  21. National Committee for Clinical Laboratory Standards (1997).Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, 4th edn. Approved standard M7 A4. Wayne, PA, USA.
  22. Nikaido, H. (1994). Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science 264, 382-388.[CrossRef] [Google Scholar]
  23. Ostroff, R. M., Wretlind, B. & Vasil, M. L. (1989). Mutations in the hemolytic-phospholipase C operon result in decreased virulence of Pseudomonas aeruginosa PAO1 grown under phosphate-limiting conditions. Infect Immun 57, 1369-1373. [Google Scholar]
  24. Poole, K., Krebes, K., McNally, C. & Neshat, S. (1993). Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol 175, 7363-7372. [Google Scholar]
  25. Poole, K., Gotoh, N., Tsujimoto, H. & 7 other authors (1996). Overexpression of the mexC-mexD-oprJ efflux operon in nfxB-type multidrug-resistant strains of Pseudomonas aeruginosa. Mol Microbiol 21, 713–724.[CrossRef] [Google Scholar]
  26. Quinn, J. P. (1998). Clinical problems posed by multiresistant nonfermenting gram-negative pathogens. Clin Infect Dis 27, S117-S124.[CrossRef] [Google Scholar]
  27. Riesenfeld, C., Everett, M., Piddock, L. J. & Hall, B. G. (1997). Adaptive mutations produce resistance to ciprofloxacin. Antimicrob Agents Chemother 41, 2059-2060. [Google Scholar]
  28. Rosenberg, S. M. (1997). Mutation for survival. Curr Opin Genet Dev 7, 829-834.[CrossRef] [Google Scholar]
  29. Saier, M. H.Jr, Paulsen, I. T., Sliwinski, M. K., Pao, S. S., Skurray, R. A. & Nikaido, H. (1998). Evolutionary origins of multidrug and drug-specific efflux pumps in bacteria. FASEB J 12, 265-274. [Google Scholar]
  30. Sferra, T. J. & Collins, F. S. (1993). The molecular biology of cystic fibrosis. Annu Rev Med 44, 133-144.[CrossRef] [Google Scholar]
  31. Shapiro, J. A. (1984). Observations on the formation of clones containing araB-lacZ cistron fusions. Mol Gen Genet 194, 79-90.[CrossRef] [Google Scholar]
  32. Shapiro, J. A. (1993). Natural genetic engineering of the bacterial genome. Curr Opin Genet Dev 3, 845-848.[CrossRef] [Google Scholar]
  33. Shapiro, J. A. (1997). Genome organization, natural genetic engineering and adaptive mutation. Trends Genet 13, 98-104.[CrossRef] [Google Scholar]
  34. Sniegowski, P. D. (1995). A test of the directed mutation hypothesis in Escherichia coli MCS2 using replica plating. J Bacteriol 177, 1119-1120. [Google Scholar]
  35. Torkelson, J., Harris, R. S., Lombardo, M. J., Nagendran, J., Thulin, C. & Rosenberg, S. M. (1997). Genome-wide hypermutation in a subpopulation of stationary-phase cells underlies recombination-dependent adaptive mutation. EMBO J 16, 3303-3311.[CrossRef] [Google Scholar]
  36. Wang, T., Tanaka, M. & Sato, K. (1998). Detection of grlA and gyrA mutations in 344 Staphylococcus aureus strains. Antimicrob Agents Chemother 42, 236-240. [Google Scholar]
  37. Wiedemann, B. & Heisig, P. (1994). Mechanisms of quinolone resistance. Infection 22, S73-S79.[CrossRef] [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-145-10-2857
Loading
/content/journal/micro/10.1099/00221287-145-10-2857
Loading

Data & Media loading...

Most cited this month 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