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.
GoGreen Membership

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 15 April 1994:
Vol. 264. no. 5157, pp. 388 - 393
DOI: 10.1126/science.8153626
Prev | Table of Contents | Next

Articles

Science, Vol 264, Issue 5157, 388-393
Copyright © 1994 by American Association for the Advancement of Science

articles

Resistance to antibiotics mediated by target alterations

BG Spratt

Microbial Genetics Group, School of Biological Sciences, University of Sussex, Falmer, Brighton, U.K.

The development of resistance to antibiotics by reductions in the affinities of their enzymatic targets occurs most rapidly for antibiotics that inactivate a single target and that are not analogs of substrate. In these cases of resistance (for example, resistance to rifampicin), numerous single amino acid substitutions may provide large decreases in the affinity of the target for the antibiotic, leading to clinically significant levels of resistance. Resistance due to target alterations should occur much more slowly for those antibiotics (penicillin, for example) that inactivate multiple targets irreversibly by acting as close analogs of substrate. Resistance to penicillin because of target changes has emerged, by unexpected mechanisms, only in a limited number of species. However, inactivating enzymes commonly provide resistance to antibiotics that, like penicillin, are derived from natural products, although such enzymes have not been found for synthetic antibiotics. Thus, the ideal antibiotic would be produced by rational design, rather than by the modification of a natural product.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Addition of Rifampin to Standard Therapy for Treatment of Native Valve Infective Endocarditis Caused by Staphylococcus aureus.
D. J. Riedel, E. Weekes, and G. N. Forrest (2008)
Antimicrob. Agents Chemother. 52, 2463-2467
   Abstract »    Full Text »    PDF »
Combined Real-Time PCR and Pyrosequencing Strategy for Objective, Sensitive, Specific, and High-Throughput Identification of Reduced Susceptibility to Penicillins in Neisseria meningitidis.
S. Thulin, P. Olcen, H. Fredlund, and M. Unemo (2008)
Antimicrob. Agents Chemother. 52, 753-756
   Abstract »    Full Text »    PDF »
Distribution and Physiology of ABC-Type Transporters Contributing to Multidrug Resistance in Bacteria.
J. Lubelski, W. N. Konings, and A. J. M. Driessen (2007)
Microbiol. Mol. Biol. Rev. 71, 463-476
   Abstract »    Full Text »    PDF »
In vitro activity of ceftaroline (PPI-0903M, T-91825) against bacteria with defined resistance mechanisms and phenotypes.
S. Mushtaq, M. Warner, Y. Ge, K. Kaniga, and D. M. Livermore (2007)
J. Antimicrob. Chemother. 60, 300-311
   Abstract »    Full Text »    PDF »
Target Gene Sequencing To Characterize the Penicillin G Susceptibility of Neisseria meningitidis.
M.-K. Taha, J. A. Vazquez, E. Hong, D. E. Bennett, S. Bertrand, S. Bukovski, M. T. Cafferkey, F. Carion, J. J. Christensen, M. Diggle, et al. (2007)
Antimicrob. Agents Chemother. 51, 2784-2792
   Abstract »    Full Text »    PDF »
Allosteric inhibition of Staphylococcus aureus D-alanine:D-alanine ligase revealed by crystallographic studies.
S. Liu, J. S. Chang, J. T. Herberg, M.-M. Horng, P. K. Tomich, A. H. Lin, and K. R. Marotti (2006)
PNAS 103, 15178-15183
   Abstract »    Full Text »    PDF »
Total Variation in the penA Gene of Neisseria meningitidis: Correlation between Susceptibility to {beta}-Lactam Antibiotics and penA Gene Heterogeneity..
S. Thulin, P. Olcen, H. Fredlund, and M. Unemo (2006)
Antimicrob. Agents Chemother. 50, 3317-3324
   Abstract »    Full Text »    PDF »
Immunogenicity of meningococcal PBP2 during natural infection and protective activity of anti-PBP2 antibodies against meningococcal bacteraemia in mice.
M. L. Zarantonelli, A. Antignac, M. Lancellotti, A. Guiyoule, J.-M. Alonso, and M.-K. Taha (2006)
J. Antimicrob. Chemother. 57, 924-930
   Abstract »    Full Text »    PDF »
Interlaboratory Comparison of PCR-Based Methods for Detection of Penicillin G Susceptibility in Neisseria meningitidis.
M.-K. Taha, M. L. Zarantonelli, A. Neri, R. Enriquez, J. A. Vazquez, and P. Stefanelli (2006)
Antimicrob. Agents Chemother. 50, 887-892
   Abstract »    Full Text »    PDF »
Distribution and Genetic Diversity of the ABC Transporter Lipoproteins PiuA and PiaA within Streptococcus pneumoniae and Related Streptococci.
R. H. Whalan, S. G. P. Funnell, L. D. Bowler, M. J. Hudson, A. Robinson, and C. G. Dowson (2006)
J. Bacteriol. 188, 1031-1038
   Abstract »    Full Text »    PDF »
Correlation between Ceftriaxone Resistance of Salmonella enterica Serovar Typhimurium and Expression of Outer Membrane Proteins OmpW and Ail/OmpX-Like Protein, Which Are Regulated by BaeR of a Two-Component System.
W. S. Hu, P.-C. Li, and C.-Y. Cheng (2005)
Antimicrob. Agents Chemother. 49, 3955-3958
   Abstract »    Full Text »    PDF »
Structural and functional characterization of CFE88: Evidence that a conserved and essential bacterial protein is a methyltransferase.
K. L. Constantine, S. R. Krystek, M. D. Healy, M. L. Doyle, N. O. Siemers, J. Thanassi, N. Yan, D. Xie, V. Goldfarb, J. Yanchunas, et al. (2005)
Protein Sci. 14, 1472-1484
   Abstract »    Full Text »    PDF »
Acquisition of Resistance to Carbapenems in Multidrug-Resistant Clinical Strains of Acinetobacter baumannii: Natural Insertional Inactivation of a Gene Encoding a Member of a Novel Family of {beta}-Barrel Outer Membrane Proteins.
M. A. Mussi, A. S. Limansky, and A. M. Viale (2005)
Antimicrob. Agents Chemother. 49, 1432-1440
   Abstract »    Full Text »    PDF »
Patterns of Antimicrobial Resistance Observed in Escherichia coli Isolates Obtained from Domestic- and Wild-Animal Fecal Samples, Human Septage, and Surface Water.
R. S. Sayah, J. B. Kaneene, Y. Johnson, and R. Miller (2005)
Appl. Envir. Microbiol. 71, 1394-1404
   Abstract »    Full Text »    PDF »
Variation of the natural transformation frequency of Campylobacter jejuni in liquid shake culture.
D. L. Wilson, J. A. Bell, V. B. Young, S. R. Wilder, L. S. Mansfield, and J. E. Linz (2003)
Microbiology 149, 3603-3615
   Abstract »    Full Text »    PDF »
Genetic Characterization of Optochin-Susceptible Viridans Group Streptococci.
A. J. Martin-Galiano, L. Balsalobre, A. Fenoll, and A. G. de la Campa (2003)
Antimicrob. Agents Chemother. 47, 3187-3194
   Abstract »    Full Text »    PDF »
Viridans Group Streptococci Are Donors in Horizontal Transfer of Topoisomerase IV Genes to Streptococcus pneumoniae.
L. Balsalobre, M. J. Ferrandiz, J. Linares, F. Tubau, and A. G. de la Campa (2003)
Antimicrob. Agents Chemother. 47, 2072-2081
   Abstract »    Full Text »    PDF »
Horizontal Acquisition of Divergent Chromosomal DNA in Bacteria: Effects of Mutator Phenotypes.
J. P. Townsend, K. M. Nielsen, D. S. Fisher, and D. L. Hartl (2003)
Genetics 164, 13-21
   Abstract »    Full Text »    PDF »
Active-Site Residues of Escherichia coli DNA Gyrase Required in Coupling ATP Hydrolysis to DNA Supercoiling and Amino Acid Substitutions Leading to Novobiocin Resistance.
C. H. Gross, J. D. Parsons, T. H. Grossman, P. S. Charifson, S. Bellon, J. Jernee, M. Dwyer, S. P. Chambers, W. Markland, M. Botfield, et al. (2003)
Antimicrob. Agents Chemother. 47, 1037-1046
   Abstract »    Full Text »    PDF »
Antimicrobial resistance in Canada.
J. Conly (2002)
Can. Med. Assoc. J. 167, 885-891
   Abstract »    Full Text »    PDF »
Overexpression of the MtrC-MtrD-MtrE Efflux Pump Due to an mtrR Mutation Is Required for Chromosomally Mediated Penicillin Resistance in Neisseria gonorrhoeae.
W. L. Veal, R. A. Nicholas, and W. M. Shafer (2002)
J. Bacteriol. 184, 5619-5624
   Abstract »    Full Text »    PDF »
Fluoroquinolone-Resistant Streptococcus pneumoniae Strains Occur Frequently in Elderly Patients in Japan.
S.-i. Yokota, K. Sato, O. Kuwahara, S. Habadera, N. Tsukamoto, H. Ohuchi, H. Akizawa, T. Himi, and N. Fujii (2002)
Antimicrob. Agents Chemother. 46, 3311-3315
   Abstract »    Full Text »    PDF »
Characterization of Inhibitor-Resistant Histone Deacetylase Activity in Plant-Pathogenic Fungi.
D. Baidyaroy, G. Brosch, S. Graessle, P. Trojer, and J. D. Walton (2002)
Eukaryot. Cell 1, 538-547
   Abstract »    Full Text »    PDF »
Methicillin resistant Staphylococcus aureus (MRSA) in the intensive care unit.
A S Haddadin, S A Fappiano, and P A Lipsett (2002)
Postgrad. Med. J. 78, 385-392
   Abstract »    Full Text »    PDF »
Response of Escherichia coli hypermutators to selection pressure with antimicrobial agents from different classes.
K. Miller, A. J. O'Neill, and I. Chopra (2002)
J. Antimicrob. Chemother. 49, 925-934
   Abstract »    Full Text »    PDF »
Development of a Procedure for Discriminating among Escherichia coli Isolates from Animal and Human Sources.
S. Guan, R. Xu, S. Chen, J. Odumeru, and C. Gyles (2002)
Appl. Envir. Microbiol. 68, 2690-2698
   Abstract »    Full Text »    PDF »
Antagonistic Interactions among Marine Pelagic Bacteria.
R. A. Long and F. Azam (2001)
Appl. Envir. Microbiol. 67, 4975-4983
   Abstract »    Full Text »
Activation of Multiple Antibiotic Resistance in Uropathogenic Escherichia coli Strains by Aryloxoalcanoic Acid Compounds.
C. Balagué and E. G. Véscovi (2001)
Antimicrob. Agents Chemother. 45, 1815-1822
   Abstract »    Full Text »
In Vitro Activities of Ertapenem (MK-0826) against Recent Clinical Bacteria Collected in Europe and Australia.
D. M. Livermore, M. W. Carter, S. Bagel, B. Wiedemann, F. Baquero, E. Loza, H. P. Endtz, N. van den Braak, C. J. Fernandes, L. Fernandes, et al. (2001)
Antimicrob. Agents Chemother. 45, 1860-1867
   Abstract »    Full Text »
Mutations of the Helicobacter pylori Genes rdxA and pbp1 Cause Resistance against Metronidazole and Amoxicillin.
R. Paul, S. Postius, K. Melchers, and K. P. Schäfer (2001)
Antimicrob. Agents Chemother. 45, 962-965
   Abstract »    Full Text »
Polymorphism of Neisseria meningitidis penA gene associated with reduced susceptibility to penicillin.
A. Antignac, P. Kriz, G. Tzanakaki, J.-M. Alonso, and M.-K. Taha (2001)
J. Antimicrob. Chemother. 47, 285-296
   Abstract »    Full Text »    PDF »
Evolution and Clinical Importance of Extended-Spectrum {beta}-Lactamases.
L. Rice (2001)
Chest 119, 391S-396S
   Abstract »    Full Text »    PDF »
A soxRS-Constitutive Mutation Contributing to Antibiotic Resistance in a Clinical Isolate of Salmonella enterica (Serovar Typhimurium).
A. Koutsolioutsou, E. A. Martins, D. G. White, S. B. Levy, and B. Demple (2001)
Antimicrob. Agents Chemother. 45, 38-43
   Abstract »    Full Text »
Molecular Properties of Bacterial Multidrug Transporters.
M. Putman, H. W. van Veen, and W. N. Konings (2000)
Microbiol. Mol. Biol. Rev. 64, 672-693
   Abstract »    Full Text »    PDF »
Long-Term Shifts in Patterns of Antibiotic Resistance in Enteric Bacteria.
T. Houndt and H. Ochman (2000)
Appl. Envir. Microbiol. 66, 5406-5409
   Abstract »    Full Text »
Diversity of PspA: Mosaic Genes and Evidence for Past Recombination in Streptococcus pneumoniae.
S. K. Hollingshead, R. Becker, and D. E. Briles (2000)
Infect. Immun. 68, 5889-5900
   Abstract »    Full Text »    PDF »
Additive effects of a two-amino-acid insertion and a single-amino-acid substitution in dihydropteroate synthase for the development of sulphonamide-resistant Neisseria meningitidis.
Y. Qvarnström and G. Swedberg (2000)
Microbiology 146, 1151-1156
   Abstract »    Full Text »
Horizontal Transfer of parC and gyrA in Fluoroquinolone-Resistant Clinical Isolates of Streptococcus pneumoniae.
M. J. Ferrándiz, A. Fenoll, J. Liñares, and A. G. De La Campa (2000)
Antimicrob. Agents Chemother. 44, 840-847
   Abstract »    Full Text »
Estimating Recombinational Parameters in Streptococcus pneumoniae From Multilocus Sequence Typing Data.
E. J. Feil, J. M. Smith, M. C. Enright, and B. G. Spratt (2000)
Genetics 154, 1439-1450
   Abstract »    Full Text »
Protein Phylogenies and Signature Sequences: A Reappraisal of Evolutionary Relationships among Archaebacteria, Eubacteria, and Eukaryotes.
R. S. Gupta (1998)
Microbiol. Mol. Biol. Rev. 62, 1435-1491
   Abstract »    Full Text »    PDF »
Identification of a structural determinant for resistance to beta -lactam antibiotics in Gram-positive bacteria.
N. Mouz, E. Gordon, A.-M. Di Guilmi, I. Petit, Y. Petillot, Y. Dupont, R. Hakenbeck, T. Vernet, and O. Dideberg (1998)
PNAS 95, 13403-13406
   Abstract »    Full Text »    PDF »
Fluoroquinolone Resistance Mutations in the parC, parE, and gyrA Genes of Clinical Isolates of Viridans Group Streptococci.
I. González, M. Georgiou, F. Alcaide, D. Balas, J. Liñares, and A. G. de la Campa (1998)
Antimicrob. Agents Chemother. 42, 2792-2798
   Abstract »    Full Text »
Therapy for Children With Invasive Pneumococcal Infections.
Committee on Infectious Diseases (1997)
Pediatrics 99, 289-299
   Abstract »    Full Text »    PDF »
Vancomycin resistance: structure of D-alanine:D-alanine ligase at 2.3 A resolution.
C Fan, P. Moews, C. Walsh, and Knox JR (1994)
Science 266, 439-443
   Abstract »    PDF »
Resistance to antibiotics.
(1994)
Science 264, 360-393
   PDF »
Prevention of drug access to bacterial targets: permeability barriers and active efflux.
H Nikaido (1994)
Science 264, 382-388
   Abstract »    PDF »
Crystal Structure of PBP2x from a Highly Penicillin-resistant Streptococcus pneumoniae Clinical Isolate. A MOSAIC FRAMEWORK CONTAINING 83 MUTATIONS.
A. Dessen, N. Mouz, E. Gordon, J. Hopkins, and O. Dideberg (2001)
J. Biol. Chem. 276, 45106-45112
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

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