Citation | Spratt's main contribution has been to the elucidation of the mechanism of action of penicillin. In particular, he developed methods for the study of the enzymes that penicillin inhibits (as penicillin-binding proteins; PBPs), and used these methods to show that the complex effects produced by beta-lactam antibiotics are due to their ability to inactivate three distinct PBPs that have specific functions in cell wall synthesis during the bacterial cell cycle. This work, and that on the physiological roles of PBPs, has been very influential and much cited. He has demonstrated that "penicillin-resistant" PBPs have evolved in penicillin-resistant clinical isolates of several bacterial species by a novel genetic mechanism, involving the replacement of parts of the PBP genes with the corresponding parts of the homologous genes from related species, to produce hybrid PBPs with decreased affinity for penicillin. This finding is of general evolutionary interest as it shows that localised recombinational events (e.g. mediated by genetic transformation or transduction) allow a bacterial species to produce novel hybrid enzymes by utilising the genetic diversity that exists both within its own species and within related species that are sufficiently similar to allow homologous recombination to occur. |