Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Science 25 February 2000:
Vol. 287. no. 5457, pp. 1479 - 1482
DOI: 10.1126/science.287.5457.1479

Reports

Effects of Environment on Compensatory Mutations to Ameliorate Costs of Antibiotic Resistance

J. Björkman, 12* I. Nagaev, 2* O. G. Berg, 3 D. Hughes, 2 D. I. Andersson 1dagger

Most types of antibiotic resistance impose a biological cost on bacterial fitness. These costs can be compensated, usually without loss of resistance, by second-site mutations during the evolution of the resistant bacteria in an experimental host or in a laboratory medium. Different fitness-compensating mutations were selected depending on whether the bacteria evolved through serial passage in mice or in a laboratory medium. This difference in mutation spectra was caused by either a growth condition-specific formation or selection of the compensated mutants. These results suggest that bacterial evolution to reduce the costs of antibiotic resistance can take different trajectories within and outside a host.

1 Department of Bacteriology, Swedish Institute for Infectious Disease Control, S-171 82 Solna, Sweden.
2 Department of Cell and Molecular Biology, Uppsala University, Biomedical Centre (BMC), Box 596, S-751 24 Uppsala, Sweden.
3 Department of Molecular Evolution, Uppsala University, BMC, Box 582, S-751 23 Uppsala, Sweden.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: Dan.Andersson{at}smi.ki.se


Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Mutational neighbourhood and mutation supply rate constrain adaptation in Pseudomonas aeruginosa.
A. R. Hall, V. F. Griffiths, R. C. MacLean, and N. Colegrave (2009)
Proc R Soc B
   Abstract »    Full Text »    PDF »
The Fitness Cost of Streptomycin Resistance Depends on rpsL Mutation, Carbon Source and RpoS ({sigma}S).
W. Paulander, S. Maisnier-Patin, and D. I. Andersson (2009)
Genetics 183, 539-546
   Abstract »    Full Text »    PDF »
The role of natural environments in the evolution of resistance traits in pathogenic bacteria.
J. L. Martinez (2009)
Proc R Soc B 276, 2521-2530
   Abstract »    Full Text »    PDF »
Lack of Evolutionary Conservation at Positions Important for Thermal Stability in the Yeast ODCase Protein.
A. Jakubowska and R. Korona (2009)
Mol. Biol. Evol. 26, 1431-1434
   Abstract »    Full Text »    PDF »
Genetic Analysis of Colistin Resistance in Salmonella enterica Serovar Typhimurium.
S. Sun, A. Negrea, M. Rhen, and D. I. Andersson (2009)
Antimicrob. Agents Chemother. 53, 2298-2305
   Abstract »    Full Text »    PDF »
Genetic Determinants of Resistance to Fusidic Acid among Clinical Bacteremia Isolates of Staphylococcus aureus.
J. Lannergard, T. Norstrom, and D. Hughes (2009)
Antimicrob. Agents Chemother. 53, 2059-2065
   Abstract »    Full Text »    PDF »
In Situ Growth Rates and Biofilm Development of Pseudomonas aeruginosa Populations in Chronic Lung Infections.
L. Yang, J. A. J. Haagensen, L. Jelsbak, H. K. Johansen, C. Sternberg, N. Hoiby, and S. Molin (2008)
J. Bacteriol. 190, 2767-2776
   Abstract »    Full Text »    PDF »
Fitness Cost and Impaired Survival in Penicillin-Resistant Streptococcus gordonii Isolates Selected in the Laboratory.
M. Haenni and P. Moreillon (2008)
Antimicrob. Agents Chemother. 52, 337-339
   Abstract »    Full Text »    PDF »
Pseudomonas aeruginosa May Accumulate Drug Resistance Mechanisms without Losing Its Ability To Cause Bloodstream Infections.
D. Hocquet, P. Berthelot, M. Roussel-Delvallez, R. Favre, K. Jeannot, O. Bajolet, N. Marty, F. Grattard, P. Mariani-Kurkdjian, E. Bingen, et al. (2007)
Antimicrob. Agents Chemother. 51, 3531-3536
   Abstract »    Full Text »    PDF »
Influence of Antibiotic Selection on Genetic Composition of Escherichia coli Populations from Conventional and Organic Dairy Farms.
S. T. Walk, J. M. Mladonicky, J. A. Middleton, A. J. Heidt, J. R. Cunningham, P. Bartlett, K. Sato, and T. S. Whittam (2007)
Appl. Envir. Microbiol. 73, 5982-5989
   Abstract »    Full Text »    PDF »
A Fitness Cost Associated With the Antibiotic Resistance Enzyme SME-1 {beta}-Lactamase.
D. C. Marciano, O. Y. Karkouti, and T. Palzkill (2007)
Genetics 176, 2381-2392
   Abstract »    Full Text »    PDF »
Caenorhabditis elegans as a Model To Determine Fitness of Antibiotic-Resistant Salmonella enterica Serovar Typhimurium.
W. Paulander, A. Pennhag, D. I. Andersson, and S. Maisnier-Patin (2007)
Antimicrob. Agents Chemother. 51, 766-769
   Abstract »    Full Text »    PDF »
Evidence of Antibiotic Resistance Gene Silencing in Escherichia coli..
V. I. Enne, A. A. Delsol, J. M. Roe, and P. M. Bennett (2006)
Antimicrob. Agents Chemother. 50, 3003-3010
   Abstract »    Full Text »    PDF »
Functional Heterogeneity of RpoS in Stress Tolerance of Enterohemorrhagic Escherichia coli Strains..
A. A. Bhagwat, J. Tan, M. Sharma, M. Kothary, S. Low, B. D. Tall, and M. Bhagwat (2006)
Appl. Envir. Microbiol. 72, 4978-4986
   Abstract »    Full Text »    PDF »
Upgrading antibiotic use within a class: Tradeoff between resistance and treatment success.
Y. C. Wang and M. Lipsitch (2006)
PNAS 103, 9655-9660
   Abstract »    Full Text »    PDF »
Reducing the fitness cost of antibiotic resistance by amplification of initiator tRNA genes.
A. I. Nilsson, A. Zorzet, A. Kanth, S. Dahlstrom, O. G. Berg, and D. I. Andersson (2006)
PNAS 103, 6976-6981
   Abstract »    Full Text »    PDF »
Role of novel gyrA mutations in the suppression of the fluoroquinolone resistance genotype of vaccine strain Salmonella Typhimurium vacT (gyrA D87G).
A. Preisler, M. A. Mraheil, and P. Heisig (2006)
J. Antimicrob. Chemother. 57, 430-436
   Abstract »    Full Text »    PDF »
Drug Resistance in Leishmaniasis.
S. L. Croft, S. Sundar, and A. H. Fairlamb (2006)
Clin. Microbiol. Rev. 19, 111-126
   Abstract »    Full Text »    PDF »
Assessment of the fitness impacts on Escherichia coli of acquisition of antibiotic resistance genes encoded by different types of genetic element.
V. I. Enne, A. A. Delsol, G. R. Davis, S. L. Hayward, J. M. Roe, and P. M. Bennett (2005)
J. Antimicrob. Chemother. 56, 544-551
   Abstract »    Full Text »    PDF »
Biological Cost of Single and Multiple Norfloxacin Resistance Mutations in Escherichia coli Implicated in Urinary Tract Infections.
P. K. Lindgren, L. L. Marcusson, D. Sandvang, N. Frimodt-Moller, and D. Hughes (2005)
Antimicrob. Agents Chemother. 49, 2343-2351
   Abstract »    Full Text »    PDF »
In Vitro Assessment of the Further Potential for Development of Fluoroquinolone Resistance in Neisseria meningitidis.
T. R. Shultz, P. A. White, and J. W. Tapsall (2005)
Antimicrob. Agents Chemother. 49, 1753-1760
   Abstract »    Full Text »    PDF »
23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A->G.
P. Pfister, N. Corti, S. Hobbie, C. Bruell, R. Zarivach, A. Yonath, and E. C. Bottger (2005)
PNAS 102, 5180-5185
   Abstract »    Full Text »    PDF »
Compensatory Adaptation to the Loss of Biological Fitness Associated with Acquisition of Fusidic Acid Resistance in Staphylococcus aureus.
S. Besier, A. Ludwig, V. Brade, and T. A. Wichelhaus (2005)
Antimicrob. Agents Chemother. 49, 1426-1431
   Abstract »    Full Text »    PDF »
Enhanced in vivo fitness of fluoroquinolone-resistant Campylobacter jejuni in the absence of antibiotic selection pressure.
N. Luo, S. Pereira, O. Sahin, J. Lin, S. Huang, L. Michel, and Q. Zhang (2005)
PNAS 102, 541-546
   Abstract »    Full Text »    PDF »
Age-Related Decline in Carriage of Ampicillin-Resistant Escherichia coli in Young Calves.
D. V. Hoyle, D. J. Shaw, H. I. Knight, H. C. Davison, M. C. Pearce, J. C. Low, G. J. Gunn, and M. E. J. Woolhouse (2004)
Appl. Envir. Microbiol. 70, 6927-6930
   Abstract »    Full Text »    PDF »
Experimental Adaptation of Salmonella typhimurium to Mice.
A. I. Nilsson, E. Kugelberg, O. G. Berg, and D. I. Andersson (2004)
Genetics 168, 1119-1130
   Abstract »    Full Text »    PDF »
Resistance in the environment.
K. Kummerer (2004)
J. Antimicrob. Chemother. 54, 311-320
   Abstract »    Full Text »    PDF »
Plasmid-encoded functions compensate for the biological cost of AmpC overexpression in a clinical isolate of Salmonella typhimurium.
A. Hossain, M. D. Reisbig, and N. D. Hanson (2004)
J. Antimicrob. Chemother. 53, 964-970
   Abstract »    Full Text »    PDF »
Emergence of phenotypic variants upon mismatch repair disruption in Pseudomonas aeruginosa.
A. M. Smania, I. Segura, R. J. Pezza, C. Becerra, I. Albesa, and C. E. Argarana (2004)
Microbiology 150, 1327-1338
   Abstract »    Full Text »    PDF »
Effect of rpoB Mutations Conferring Rifampin Resistance on Fitness of Mycobacterium tuberculosis.
D. H. Mariam, Y. Mengistu, S. E. Hoffner, and D. I. Andersson (2004)
Antimicrob. Agents Chemother. 48, 1289-1294
   Abstract »    Full Text »    PDF »
Overexpression of the multidrug efflux pump SmeDEF impairs Stenotrophomonas maltophilia physiology.
A. Alonso, G. Morales, R. Escalante, E. Campanario, L. Sastre, and J. L. Martinez (2004)
J. Antimicrob. Chemother. 53, 432-434
   Abstract »    Full Text »    PDF »
Fusidic Acid-Resistant Mutants of Salmonella enterica Serovar Typhimurium with Low Fitness In Vivo Are Defective in RpoS Induction.
M. Macvanin, J. Bjorkman, S. Eriksson, M. Rhen, D. I. Andersson, and D. Hughes (2003)
Antimicrob. Agents Chemother. 47, 3743-3749
   Abstract »    Full Text »    PDF »
Quinolone Resistance Due to Reduced Target Enzyme Expression.
D. Ince and D. C. Hooper (2003)
J. Bacteriol. 185, 6883-6892
   Abstract »    Full Text »    PDF »
Amelioration of the Cost of Conjugative Plasmid Carriage in Eschericha coli K12.
C. Dahlberg and L. Chao (2003)
Genetics 165, 1641-1649
   Abstract »    Full Text »    PDF »
Collateral Damage.
L. B. Rice (2003)
Ann Intern Med 139, 523-524
   Full Text »    PDF »
Jumping the Barrier to {beta}-Lactam Resistance in Staphylococcus aureus.
Y. Katayama, H.-Z. Zhang, D. Hong, and H. F. Chambers (2003)
J. Bacteriol. 185, 5465-5472
   Abstract »    Full Text »    PDF »
Biological Costs and Mechanisms of Fosfomycin Resistance in Escherichia coli.
A. I. Nilsson, O. G. Berg, O. Aspevall, G. Kahlmeter, and D. I. Andersson (2003)
Antimicrob. Agents Chemother. 47, 2850-2858
   Abstract »    Full Text »    PDF »
Horizontal gene transfer: A critical view.
C. G. Kurland, B. Canback, and O. G. Berg (2003)
PNAS 100, 9658-9662
   Abstract »    Full Text »    PDF »
Fitness of antibiotic resistant Staphylococcus epidermidis assessed by competition on the skin of human volunteers.
I. Gustafsson, O. Cars, and D. I. Andersson (2003)
J. Antimicrob. Chemother. 52, 258-263
   Abstract »    Full Text »    PDF »
Fitness cost of fluoroquinolone resistance in Salmonella enterica serovar Typhimurium.
E. Giraud, A. Cloeckaert, S. Baucheron, C. Mouline, and E. Chaslus-Dancla (2003)
J. Med. Microbiol. 52, 697-703
   Abstract »    Full Text »    PDF »
Cefuroxime resistance in non-{beta}-lactamase Haemophilus influenzae is linked to mutations in ftsI.
K. Straker, M. Wootton, A. M. Simm, P. M. Bennett, A. P. MacGowan, and T. R. Walsh (2003)
J. Antimicrob. Chemother. 51, 523-530
   Abstract »    Full Text »    PDF »
Different Spectra of Stationary-Phase Mutations in Early-Arising versus Late-Arising Mutants of Pseudomonas putida: Involvement of the DNA Repair Enzyme MutY and the Stationary-Phase Sigma Factor RpoS.
S. Saumaa, A. Tover, L. Kasak, and M. Kivisaar (2002)
J. Bacteriol. 184, 6957-6965
   Abstract »    Full Text »    PDF »
Evolution of Microbial Genomes: Sequence Acquisition and Loss.
O. G. Berg and C. G. Kurland (2002)
Mol. Biol. Evol. 19, 2265-2276
   Abstract »    Full Text »    PDF »
Biological Cost of Rifampin Resistance from the Perspective of Staphylococcus aureus.
T. A. Wichelhaus, B. Boddinghaus, S. Besier, V. Schafer, V. Brade, and A. Ludwig (2002)
Antimicrob. Agents Chemother. 46, 3381-3385
   Abstract »    Full Text »    PDF »
Fitness of in vitro selected Pseudomonas aeruginosanalB and nfxB multidrug resistant mutants.
P. Sanchez, J. F. Linares, B. Ruiz-Diez, E. Campanario, A. Navas, F. Baquero, and J. L. Martinez (2002)
J. Antimicrob. Chemother. 50, 657-664
   Abstract »    Full Text »    PDF »
Interactions among Strategies Associated with Bacterial Infection: Pathogenicity, Epidemicity, and Antibiotic Resistance.
J. L. Martinez and F. Baquero (2002)
Clin. Microbiol. Rev. 15, 647-679
   Abstract »    Full Text »    PDF »
Stress-Based Identification and Classification of Antibacterial Agents: Second-Generation Escherichia coli Reporter Strains and Optimization of Detection.
E. Shapiro and F. Baneyx (2002)
Antimicrob. Agents Chemother. 46, 2490-2497
   Abstract »    Full Text »    PDF »
Molecular epidemiology of tuberculosis.
M.V. Burgos and A.S. Pym (2002)
Eur. Respir. J. 20, 54S-65s
   Abstract »    Full Text »    PDF »
Fitness Cost of Chromosomal Drug Resistance-Conferring Mutations.
P. Sander, B. Springer, T. Prammananan, A. Sturmfels, M. Kappler, M. Pletschette, and E. C. Bottger (2002)
Antimicrob. Agents Chemother. 46, 1204-1211
   Abstract »    Full Text »    PDF »
Mutator Bacteria as a Risk Factor in Treatment of Infectious Diseases.
A. Giraud, I. Matic, M. Radman, M. Fons, and F. Taddei (2002)
Antimicrob. Agents Chemother. 46, 863-865
   Abstract »    Full Text »    PDF »
Experimental Genomic Evolution: Extensive Compensation for Loss of DNA Ligase Activity in a Virus.
D. Rokyta, M. R. Badgett, I. J. Molineux, and J. J. Bull (2002)
Mol. Biol. Evol. 19, 230-238
   Abstract »    Full Text »    PDF »
Evolution of Drug Resistance in Mycobacterium tuberculosis: Clinical and Molecular Perspective.
S. H. Gillespie (2002)
Antimicrob. Agents Chemother. 46, 267-274
   Full Text »    PDF »
High Frequency of Mutator Strains among Human Uropathogenic Escherichia coli Isolates.
E. Denamur, S. Bonacorsi, A. Giraud, P. Duriez, F. Hilali, C. Amorin, E. Bingen, A. Andremont, B. Picard, F. Taddei, et al. (2002)
J. Bacteriol. 184, 605-609
   Abstract »    Full Text »    PDF »
Mutation frequency and biological cost of antibiotic resistance in Helicobacter pylori.
B. Bjorkholm, M. Sjolund, P. G. Falk, O. G. Berg, L. Engstrand, and D. I. Andersson (2001)
PNAS
   Abstract »    Full Text »    PDF »
Development of Saccharomyces cerevisiae as a Model Pathogen: A System for the Genetic Identification of Gene Products Required for Survival in the Mammalian Host Environment.
A. L. Goldstein and J. H. McCusker (2001)
Genetics 159, 499-513
   Abstract »    Full Text »    PDF »
Divergence in Fitness and Evolution of Drug Resistance in Experimental Populations of Candida albicans.
L. E. Cowen, L. M. Kohn, and J. B. Anderson (2001)
J. Bacteriol. 183, 2971-2978
   Abstract »    Full Text »    PDF »
Use of Mutator Strains for Characterization of Novel Antimicrobial Agents.
A. J. O'Neill, I. Chopra, J. L. Martinez, and F. Baquero (2001)
Antimicrob. Agents Chemother. 45, 1599-1600
   Full Text »    PDF »
Fitness and competitive growth advantage of new gentamicin-susceptible MRSA clones spreading in French hospitals.
F. Laurent, H. Lelievre, M. Cornu, F. Vandenesch, G. Carret, J. Etienne, and J.-P. Flandrois (2001)
J. Antimicrob. Chemother. 47, 277-283
   Abstract »    Full Text »    PDF »
Compensatory Evolution in Rifampin-Resistant Escherichia coli.
M. G. Reynolds (2000)
Genetics 156, 1471-1481
   Abstract »    Full Text »
Mutation Frequencies and Antibiotic Resistance.
J. L. Martinez and F. Baquero (2000)
Antimicrob. Agents Chemother. 44, 1771-1777
   Full Text »    PDF »
Mutation frequency and biological cost of antibiotic resistance in Helicobacter pylori.
B. Bjorkholm, M. Sjolund, P. G. Falk, O. G. Berg, L. Engstrand, and D. I. Andersson (2001)
PNAS 98, 14607-14612
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)