
f Emergence of multidrug-resistant mutants is increased under antibiotic selective pressure in Pseudomonas aeruginosa
- Authors: Ana Alonso1 , Ester Campanario1 , José L. Martı́nez1
-
- VIEW AFFILIATIONS
-
1 Departamento de Biotecnologı́a Microbiana, Centro Nacional de Biotecnologı́a (CSIC), Campus UAM, Cantoblanco, 28049 Madrid, Spain1
- Author for correspondence: José L. Martı́nez. Tel: +34 91 5854539. Fax: +34 91 5854506. e-mail: [email protected]
- First Published Online: 01 October 1999, Microbiology 145: 2857-2862, doi: 10.1099/00221287-145-10-2857
- Subject: Pathogenicity And Medical Microbiology
- Received:
- Accepted:
- Revised:
- Cover date:




Emergence of multidrug-resistant mutants is increased under antibiotic selective pressure in Pseudomonas aeruginosa, Page 1 of 1
< Previous page | Next page > /docserver/preview/fulltext/micro/145/10/1452857a-1.gif
-
Pseudomonas aeruginosa 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 P. aeruginosa 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 P. aeruginosa 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 P. aeruginosa strain PAO1. These data are consistent with the hypothesis that incubation in the presence of tetracycline favours the emergence of MDR mutants in P. aeruginosa. 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.
- Keyword(s): antibiotic resistance, MDR, MDR, multidrug resistance, Pseudomonas aeruginosa, adaptive mutation, mutation rate
-
Baquero, F. & Blazquez, J. ( 1997; ). Evolution of antibiotic resistance. Trends Ecol Evol 12, 482-487.[CrossRef]
-
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.
-
Bonhoeffer, S., Lipsitch, M. & Levin, B. R. ( 1997; ). Evaluating treatment protocols to prevent antibiotic resistance. Proc Natl Acad Sci USA 94, 12106-12111.[CrossRef]
-
Cairns, J. & Foster, P. L. ( 1991; ). Adaptive reversion of a frameshift mutation in Escherichia coli. Genetics 128, 695-701.
-
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]
-
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.
-
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.
-
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]
-
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]
-
Govan, J. R. & Nelson, J. W. ( 1992; ). Microbiology of lung infection in cystic fibrosis. Br Med Bull 48, 912-930.
-
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.
-
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]
-
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]
-
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]
-
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.
-
McKenzie, G. J., Lombardo, M. J. & Rosenberg, S. M. ( 1998; ). Recombination-dependent mutation in Escherichia coli occurs in stationary phase. Genetics 149, 1163-1165.
-
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.
-
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]
-
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]
-
Nikaido, H. ( 1994; ). Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science 264, 382-388.[CrossRef]
-
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.
-
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.
-
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]
-
Quinn, J. P. ( 1998; ). Clinical problems posed by multiresistant nonfermenting gram-negative pathogens. Clin Infect Dis 27, S117-S124.[CrossRef]
-
Riesenfeld, C., Everett, M., Piddock, L. J. & Hall, B. G. ( 1997; ). Adaptive mutations produce resistance to ciprofloxacin. Antimicrob Agents Chemother 41, 2059-2060.
-
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.
-
Sferra, T. J. & Collins, F. S. ( 1993; ). The molecular biology of cystic fibrosis. Annu Rev Med 44, 133-144.[CrossRef]
-
Shapiro, J. A. ( 1984; ). Observations on the formation of clones containing araB-lacZ cistron fusions. Mol Gen Genet 194, 79-90.[CrossRef]
-
Shapiro, J. A. ( 1993; ). Natural genetic engineering of the bacterial genome. Curr Opin Genet Dev 3, 845-848.[CrossRef]
-
Shapiro, J. A. ( 1997; ). Genome organization, natural genetic engineering and adaptive mutation. Trends Genet 13, 98-104.[CrossRef]
-
Sniegowski, P. D. ( 1995; ). A test of the directed mutation hypothesis in Escherichia coli MCS2 using replica plating. J Bacteriol 177, 1119-1120.
-
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]
-
Wang, T., Tanaka, M. & Sato, K. ( 1998; ). Detection of grlA and gyrA mutations in 344 Staphylococcus aureus strains. Antimicrob Agents Chemother 42, 236-240.
-
Wiedemann, B. & Heisig, P. ( 1994; ). Mechanisms of quinolone resistance. Infection 22, S73-S79.[CrossRef]

Supplementary Data
Data loading....

Article metrics loading...

Full text loading...
Author and Article Information
-
This Journal
/content/journal/micro/10.1099/00221287-145-10-2857dcterms_title,dcterms_subject,pub_serialTitlepub_serialIdent:journal/micro AND -contentType:BlogPost104 -
Other Society Journals
/content/journal/micro/10.1099/00221287-145-10-2857dcterms_title,dcterms_subject-pub_serialIdent:journal/micro AND -contentType:BlogPost104 -
PubMed
-
Google Scholar
Figure data loading....