Antibiotic Resistance Mechanisms, with an Emphasis on Those Related to the Ribosome

Antibiotic resistance is a fundamental aspect of microbiology, but it is also a phenomenon of vital importance in the treatment of diseases caused by pathogenic microorganisms. A resistance mechanism can involve an inherent trait or the acquisition of a new characteristic through either mutation or horizontal gene transfer. The natural susceptibilities of bacteria to a certain drug vary significantly from one species of bacteria to another and even from one strain to another. Once inside the cell, most antibiotics affect all bacteria similarly. The ribosome is a major site of antibiotic action and is targeted by a large and chemically diverse group of antibiotics. A number of these antibiotics have important applications in human and veterinary medicine in the treatment of bacterial infections. The antibiotic binding sites are clustered at functional centers of the ribosome, such as the decoding center, the peptidyl transferase center, the GTPase center, the peptide exit tunnel, and the subunit interface spanning both subunits on the ribosome. Upon binding, the drugs interfere with the positioning and movement of substrates, products, and ribosomal components that are essential for protein synthesis. Ribosomal antibiotic resistance is due to the alteration of the antibiotic binding sites through either mutation or methylation. Our knowledge of antibiotic resistance mechanisms has increased, in particular due to the elucidation of the detailed structures of antibiotic-ribosome complexes and the components of the efflux systems. A number of mutations and methyltransferases conferring antibiotic resistance have been characterized. These developments are important for understanding and approaching the problems associated with antibiotic resistance, including design of antimicrobials that are impervious to known bacterial resistance mechanisms.