Dissemination of antibiotic resistance - Genetic engineering at work among bacteria

While antibiotics have, for the past fifty years, been ''miracle drugs'', we are presently facing the end of the miracle. The increasing use of antibiotics has led to the selection of bacteria resistant to multiple antibiotics. Diverse mechanisms of resistance are found in resistant bacteria. Among these are enzymatic degradation or alteration of antibiotic molecules (e.g. beta-lactamases and aminoglycoside modifying enzymes), altered targets (e.g. penicillin-binding proteins and dihydrofolate reductase), and drug efflux (e.g: of tetracycline). Often point mutations can drastically alter the enzyme or the target: beta-lactamases become able to digest third-generation cephalosporins, dihydrofolate reductase becomes resistant to trimethoprim, and DNA gyrase becomes resistant to quinolones. Resistance genes have not always been present in common pathogenic bacteria, but have been evolving in antibiotic producing bacteria or in those cohabiting with them in the environment, and have recently been acquired by horizontal transfer. Many resistance genes are on conjugative plasmids of wide host range, often as part of transposons, Examples are the TEM beta-lactamase, whose gene can mutate to yield resistance to third-generation cephalosporins, and vancomycin resistance in enterococci, where a complete metabolic pathway for an altered cell wall is encoded by a transposon. In addition, a novel DNA element called an integron has been described, in which individual resistance genes exist as mobile cassettes and are rearranged by site-specific recombination, in a sort of natural genetic engineering, to form strongly expressed multiresistance operons. Knowledge of the mechanisms of resistance gene evolution and dissemination and of antibiotic usage patterns leads to the prediction, in a more or less immediate future, of the emergence of vancomycin-resistant staphylococci, of multiresistant pneumococci, and of third-generation-cephalosporin-resistant Haemophilus and Neisseria, for which the medical community must be prepared.