The cost of antibiotic resistance--from the perspective of a bacterium.

The possession of an antibiotic resistance gene clearly benefits a bacterium when the corresponding antibiotic is present. But does the resistant bacterium suffer a cost of resistance (i.e. a reduction in fitness) when the antibiotic is absent? If so, then one strategy to control the spread of resistance would be to suspend the use of a particular antibiotic until resistant genotypes declined to low frequency. Numerous studies have indeed shown that resistant genotypes are less fit than their sensitive counterparts in the absence of antibiotic, indicating a cost of resistance. But there is an important caveat: these studies have put antibiotic resistance genes into naïve bacteria, which have no evolutionary history of association with the resistance genes. An important question, therefore, is whether bacteria can overcome the cost of resistance by evolving adaptations that counteract the harmful side-effects of resistance genes. In fact, several experiments have shown that the cost of antibiotic resistance may be substantially diminished, even eliminated, by evolutionary changes in bacteria over rather short periods of time. As a consequence of this adaptation of bacteria to their resistance genes, it becomes increasingly difficult to eliminate resistant genotypes simply by suspending the use of antibiotics.

[1]  S. Schrag,et al.  Reducing antibiotic resistance , 1996, Nature.

[2]  L. Luzzatto,et al.  Escherichia coli: High Resistance or Dependence on Streptomycin Produced by the Same Allele , 1968, Science.

[3]  C. Gross,et al.  Characterization of the pleiotropic phenotypes of rifampin-resistant rpoB mutants of Escherichia coli , 1989, Journal of bacteriology.

[4]  R. Lenski,et al.  Constraints on the Coevolution of Bacteria and Virulent Phage: A Model, Some Experiments, and Predictions for Natural Communities , 1985, The American Naturalist.

[5]  W. Arber,et al.  Bleomycin-resistance gene derived from the transposon Tn5 confers selective advantage to Escherichia coli K-12. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[6]  R. Lenski,et al.  Effects of carriage and expression of the Tn10 tetracycline-resistance operon on the fitness of Escherichia coli K12. , 1989, Molecular biology and evolution.

[7]  M. E. Brown,et al.  A mathematical method for analysing plasmid stability in micro-organisms. , 1987, Journal of general microbiology.

[8]  H. Smith,et al.  Persistence of tetracycline resistance in pig E. coli , 1975, Nature.

[9]  G. Sundin,et al.  Dissemination of the strA‐strB streptomycin‐resistance genes among commensal and pathogenic bacteria from humans, animals, and plants , 1996, Molecular ecology.

[10]  J. Bailey,et al.  Theoretical growth yield estimates for recombinant cells. , 1986, Biotechnology and bioengineering.

[11]  R. Lenski,et al.  Genetic analysis of a plasmid-encoded, host genotype-specific enhancement of bacterial fitness , 1994, Journal of bacteriology.

[12]  A. F. Bennett,et al.  Experimental tests of the roles of adaptation, chance, and history in evolution. , 1995, Science.

[13]  Julian Adams,et al.  COEVOLUTION IN BACTERIAL‐PLASMID POPULATIONS , 1991, Evolution; international journal of organic evolution.

[14]  S Falkow,et al.  Molecular characterization of two beta-lactamase-specifying plasmids isolated from Neisseria gonorrhoeae , 1977, Journal of bacteriology.

[15]  J. E. Bouma,et al.  Effects of segregation and selection on instability of plasmid pACYC184 in Escherichia coli B , 1987, Journal of bacteriology.

[16]  G. Lebek,et al.  Generation time-prolonging R plasmids: correlation between increases in the generation time of Escherichia coli caused by R plasmids and their molecular size. , 1980, Plasmid.

[17]  F. Cohan,et al.  AMELIORATION OF THE DELETERIOUS PLEIOTROPIC EFFECTS OF AN ADAPTIVE MUTATION IN BACILLUS SUBTILIS , 1994, Evolution; international journal of organic evolution.

[18]  T. A. Krulwich,et al.  Na+/H+ antiport activity conferred by Bacillus subtilis tetA(L), a 5' truncation product of tetA(L), and related plasmid genes upon Escherichia coli , 1996, Antimicrobial Agents and Chemotherapy.

[19]  B. Berger,et al.  Effect of sulbactam on infections caused by imipenem-resistant Acinetobacter calcoaceticus biotype anitratus. , 1993, The Journal of infectious diseases.

[20]  B. Levin Conditions for the Existence of R-Plasmids in Bacterial Populations , 1980 .

[21]  B. Levin,et al.  The Evolution of Plasmids Carrying Multiple Resistance Genes: The Role of Segregation, Transposition, and Homologous Recombination , 1990, The American Naturalist.

[22]  R. Lenski EXPERIMENTAL STUDIES OF PLEIOTROPY AND EPISTASIS IN ESCHERICHIA COLI. II. COMPENSATION FOR MALADAPTIVE EFFECTS ASSOCIATED WITH RESISTANCE TO VIRUS T4 , 1988, Evolution; international journal of organic evolution.

[23]  G. Döring,et al.  Interference of ciprofloxacin with the expression of pathogenicity factors of Pseudomonas aeruginosa , 1985 .

[24]  J. E. Bouma,et al.  Evolution of a bacteria/plasmid association , 1988, Nature.

[25]  R. Williams,et al.  Reversal of Antibiotic Resistance in Hospital Staphylococcal Infection , 1960, British medical journal.

[26]  J. A. Mckenzie,et al.  The effect of genetic background on the fitness of diazinon resistance genotypes of the Australian sheep blowfly, Lucilia cuprina , 1982, Heredity.

[27]  M. Yarmolinsky,et al.  Addiction protein Phd of plasmid prophage P1 is a substrate of the ClpXP serine protease of Escherichia coli. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[28]  J. Adams,et al.  The ecology and evolution of tetracycline resistance. , 1992, Trends in ecology & evolution.

[29]  R. Lenski,et al.  Stability of recombinant DNA and its effects on fitness. , 1988, Trends in Ecology & Evolution.