Resistance to antibiotics mediated by target alterations.

@article{Spratt1994ResistanceTA,
  title={Resistance to antibiotics mediated by target alterations.},
  author={Brian G. Spratt},
  journal={Science},
  year={1994},
  volume={264 5157},
  pages={
          388-93
        }
}
  • B. Spratt
  • Published 15 April 1994
  • Biology
  • Science
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… 

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References

SHOWING 1-10 OF 60 REFERENCES

Inactivation of antibiotics and the dissemination of resistance genes.

Although bacterial conjugation once was believed to be restricted in host range, it now appears that this mechanism of transfer permits genetic exchange between many different bacterial genera in nature.

Escherichia coli resistance to β-lactam antibiotics through a decrease in the affinity of a target for lethality

The characterisation of a mutant that has gained resistance to some β-lactams by a decrease in the affinity of such a target is reported.

Resistance to β-lactam antibiotics by re-modelling the active site of an E. coli penicillin-binding protein

It is shown that only four amino-acid substitutions need to be introduced into P BP 3 of E. coli to produce a strain possessing substantial levels of resistance to a wide variety of cephalosporins, and that transfer of the gene encoding the resistant PBP 3 from the chromosome to a plasmid could result in the spread of intrinsic resistance.

Prevention of drug access to bacterial targets: permeability barriers and active efflux.

As the pharmaceutical industry succeeds in producing agents that can overcome specific mechanisms of bacterial resistance, less specific resistance mechanisms such as permeability barriers and multidrug active efflux may become increasingly significant in the clinical setting.

Amino acid substitutions that reduce the affinity of penicillin-binding protein 3 of Escherichia coli for cephalexin.

A large number of cephalexin-resistant mutants of Escherichia coli in which the resistance is due to the production of altered forms of penicillin-binding protein 3 that have reduced affinity for the antibiotic are isolated.

Discovery and development of new antibiotics: the problem of antibiotic resistance

Empiric therapy favors the use and hence the development of broad-spectrum agents and combinations, even though the underlying need may be for treatment of specific problem pathogens, such as Pseudomonas species or methicillin-resistant staphylococci.

The Crisis in Antibiotic Resistance

  • H. Neu
  • Medicine, Biology
    Science
  • 1992
Mechanisms such as antibiotic control programs, better hygiene, and synthesis of agents with improved antimicrobial activity need to be adopted in order to limit bacterial resistance.

New mechanisms of bacterial resistance to antimicrobial agents.

Resistance to antimicrobial agents affects the antibiotic options available to every practitioner and is no less a problem in the developing world.

Genetics of resistance in a non-beta-lactamase-producing gonococcus with relatively high-level penicillin resistance

A penicillin-resistant (Penr) non-penicillinase-producing Neisseria gonorrhoeae strain responsible for an outbreak affecting 199 persons in Durham, N.C., in 1983 was studied and was found to be partially due to mutations genotypically and phenotypically similar to the previously characterized chromosomal loci penA, mtr, and penB.

Genetics of resistance to third‐generation cephalosporins in clinical isolates of Streptococcus pneumoniae

Resistance to third‐generation cephalosporins in a clinical isolate of Streptococcus pneumoniae was shown to be due to the production of altered forms of penicillin‐binding proteins (PBPs) 2X and 1A.
...