Inactivation of Antibiotics and the Dissemination of Resistance Genes

• Published in: Science (American Association for the Advancement of Science) Vol. 264; no. 5157; pp. 375 - 382
• Main Author: Davies, Julian
• Format: Journal Article
• Language: English
• Published: United States American Society for the Advancement of Science 15.04.1994; American Association for the Advancement of Science
• Subjects: Amino Acid Sequence; Aminoglycosides; Anti-Bacterial Agents - antagonists & inhibitors; Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Antibiotics; Bacteria; Bacteria, Pathogenic; beta-Lactamases - genetics; beta-Lactamases - metabolism; beta-Lactams; Chloramphenicol O-Acetyltransferase - genetics; Chloramphenicol O-Acetyltransferase - metabolism; Drug resistance in microorganisms; Drug Resistance, Microbial - genetics; Enzymes; Frontiers in Biotechnology: Resistance to Antibiotics; Gene Transfer Techniques; Genes; Genes, Bacterial; Genetic aspects; Microbial drug resistance; Microorganisms; Molecular Sequence Data; Mutation; Pathogenic bacteria; Plasmids; R Factors; Recombination, Genetic; Resistance mechanisms; Transposons
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.8153624

The emergence of multidrug-resistant bacteria is a phenomenon of concern to the clinician and the pharmaceutical industry, as it is the major cause of failure in the treatment of infectious diseases. The most common mechanism of resistance in pathogenic bacteria to antibiotics of the aminoglycoside, β-lactam (penicillins and cephalosporins), and chloramphenicol types involves the enzymic inactivation of the antibiotic by hydrolysis or by formation of inactive derivatives. Such resistance determinants most probably were acquired by pathogenic bacteria from a pool of resistance genes in other microbial genera, including antibiotic-producing organisms. The resistance gene sequences were subsequently integrated by site-specific recombination into several classes of naturally occurring gene expression cassettes (typically "integrons") and disseminated within the microbial population by a variety of gene transfer mechanisms. 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.