Biochemistry and Molecular Biology - Belyasova N.A. 2002

Metabolism. Processes Requiring Energy Input
Biological Role and Regularities of Antibiotic Biosynthesis
Mechanisms of Microbial Resistance to Antibiotics

As already noted, Antibiotics exhibit selective action, affecting only certain groups of microorganisms (those sensitive to a given antibiotic) while leaving others unaffected (resistant ones). However, in populations of microorganisms sensitive to a particular antibiotic, a certain number of antibiotic-resistant variants can always be found, which arise As a result of Mutations or genetic exchange. Antibiotic Resistance can be driven by the following main factors:

1) conversion of active antibiotic forms into inactive ones by specific Enzymes. For example, Penicillins and Cephalosporins are cleaved by ß-lactamases, and chloramphenicol undergoes Acetylation, resulting in a loss of activity;

2) Modification of the target sensitive to the given antibiotic. For instance, an amino acid substitution in the S12 protein of the 30S ribosomal subunit prevents streptomycin from binding to it and blocking Translation initiation; altering The Structure of the prokaryotic DNA-dependent RNA polymerase renders them resistant to rifampicin; methylation of the 23S ribosomal RNA in the 50S ribosomal subunit makes Protein Synthesis insensitive to erythromycin and lincomycin, etc.;

3) loss or reduced permeability of Membranes and Cell Walls to antibiotics. Thus, the synthesis of Proteins affecting tetracycline transport into The Cell leads to a decrease in the intracellular concentration of these antibiotics;

4) utilization of an alternative enzyme or metabolic pathway to bypass the one inactivated by the antibiotic;

5) overexpression of the enzyme targeted by antibiotic inhibition;

6) increased concentration of a metabolite capable of counteracting the antibiotic;

7) decreased cellular requirement for the product whose synthesis is controlled by the antibiotic.

It is important to note that the Mechanisms of Antibiotic resistance determined by plasmid genes (as part of R-factors) often differ from those controlled by chromosomal genes for the same drugs. Thus, Cells inheriting R-Plasmids generally exhibit resistance to streptomycin and other aminoglycoside antibiotics through specific enzymes that inactivate the antibiotic molecules. Specifically, resistance to streptomycin in this case results from the modification of the antibiotic itself via adenylylation or phosphorylation, rather than the target of its action (the 30S ribosomal subunit).

The Study of R-plasmids suggests their rapid evolution toward an increasing number of resistance determinants. This phenomenon leads to The Emergence of plasmids that confer multidrug resistance (resistance to three, four, or more antibiotics). This may be caused by the migration of drug-resistance Transposons within populations of clinical bacterial strains, which, in turn, is driven by the widespread use of common medications. Drug-resistance transposons may also carry multiple resistance determinants, such as Tn 1696, which confers resistance to streptomycin, chloramphenicol, gentamicin, sulfonamide, and mercury ions.

Microbial strains that are superproducers of antibiotics generally possess multiple defense systems against their own antimicrobial products.