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Biochem Pharmacol. 2011 Jul 1;82(1):43-52. doi: 10.1016/j.bcp.2011.03.028. Epub 2011 Apr 8.

Development of screening assays and discovery of initial inhibitors of pneumococcal peptidoglycan deacetylase PgdA.

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  • 1Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, United Kingdom.


The essential cell wall peptidoglycan is the target of several components of the innate immune system and its disruption results in lysis of invading bacteria. The pathogen Streptococcus pneumoniae produces a peptidoglycan N-acetylglucosamine deacetylase, PgdA, to modify the peptidoglycan structure. The activity of PgdA contributes to the bacteria's resistance to lysozyme, which is an important antimicrobial factor of the human innate immune system. In this study we report on the activity of PgdA against natural and artificial substrates. We have also established a virtual high-throughput screening and a new enzyme assay to search for compounds inhibiting PgdA. Two compounds with IC(50) values in the micromolar range have been identified and they could serve as leads for the search of inhibitors of PgdA, an important pneumococcal virulence factor.

Copyright © 2011 Elsevier Inc. All rights reserved.

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