Molecular mechanisms of antibiotic resistance in gram-positive pathogens.
The widespread and uncontrolled use of antibiotics, both for human consumption and animal feed, has encouraged the development of drug resistance in a variety of pathogenic bacteria. Gram-positive species employ resistance mechanisms which include the modification of the antibiotic structure, mutagenesis of key amino acids in the macromolecular targets of specific chemotherapeutics, or drug efflux from the cell, among others. These three main mechanisms have been identified in resistance profiles for systems involved in protein biosynthesis, nucleic acid replication, and bacterial cell wall generation. This work will review how Gram-positive bacteria have manipulated all three classes of targets in the generation of resistance. Upcoming and recently approved antibacterials for human consumption will also be highlighted.
Dessen
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Laboratoire de Cristallographie Macromoléculaire, Institut de Biologie Structurale Jean-Pierre Ebel (CNRS/CEA), 41, rue Jules Horowitz, 38027 Grenoble, France. dessen@ibs.fr
Di Guilmi
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AM
Vernet
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Dideberg
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D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D002352:Carrier Proteins / Q000737:chemistry / Q000187:drug effects; D002473:Cell Wall / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D024881:Drug Resistance, Bacterial; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D016296:Mutagenesis; D046915:Penicillin-Binding Proteins; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; C072223:PBP 2x protein, Streptococcus