Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Exploring peptidoglycan biosynthesis and it’s inhibition

Penicillin and the wider family of beta-lactams have remained the single most important family of antibiotics since their introduction in the early 1940s. Unfortunately they are becoming less effective due to the emergence of resistance that now has an impact globally (1). Predominantly, resistance is mediated by reducing the target drug concentration by catalysing their inactivation by beta-lactamases( 2-4 5, 6), by increasing efflux, or reducing permeation (in Gram negative bacteria). The periplasmic/extracytoplasmic targets of penicillin are a family of enzymes with a highly conserved catalytic activity involved in the final stage of bacterial cell wall biosynthesis: cross-linking of the structural polymer peptidoglycan (PG). These enzymes, named after their ability to bind penicillin, rather than their catalytic activity are called penicillin-binding proteins (PBPs) (7-9). Surprisingly, given the pivotal importance of PBPs, we still have a very incomplete picture of how PBPs interact with their natural substrates, precisely what these substrates are, exactly how beta-lactam antibiotics interfere with this process and the response of bacteria to generate a further resistance mechanism, PBP mediated resistance.

Here we discuss recent advances in the development of new reagents assays and structures that are helping to develop a rigorous biochemical structure functional analysis of how the targets of penicillin work, including a full kinetic characterization, and the interplay between enzyme substrate and inhibitor.


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Adrian Lloyd
Dom Bellini
Hector Newman
Christopher Dowson

School of Life Sciences
University of Warwick
Coventry CV47AJ UK

Ph: (+44) 2476423534
Email: c.g.dowson@warwick.ac.uk