Penicillin binding proteins, beta-lactams, and lactamases: offensives, attacks, and defensive countermeasures.
A strong outer covering of peptidoglycan (the sacculus) is essential for most bacteria. Beta-lactams have evolved billions of years ago and can block saccular growth of the organism. This led to the evolution of beta-lactamases and resistant penicillin binding proteins (PBPs). With the introduction of lactam antibiotics by the pharmaceutical industry, resistance genes in nature were laterally transferred to antibiotic-treated disease-causing organisms and additional modification of beta-lactamase genes and of the regulatory genes of the mecA region took place. However, it can be concluded that very little of either type of resistance mechanisms represents new basic evolution against the penicillin type antibiotics. In the last 60 years the resistant bacteria in the main arose by movement of genes from other organisms, from minor genetic changes, and from alteration of the regulation of synthesis.
Koch
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Biology Department, Indiana University, Bloomington 47405-6801, USA. Koch@Indiana.edu
D001419:Bacteria / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D006602:Hexosyltransferases; D006868:Hydrolysis; D008958:Models, Molecular; D002267:Muramoylpentapeptide Carboxypeptidase / Q000737:chemistry / Q000378:metabolism*; D010403:Penicillin Resistance; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism*; D010458:Peptidyl Transferases / Q000378:metabolism; D013329:Structure-Activity Relationship; D018440:beta-Lactam Resistance / Q000235:genetics; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D047090:beta-Lactams / Q000378:metabolism* / Q000494:pharmacology
D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D047090:beta-Lactams; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases