Wzy-Dependent Bacterial Capsules as Potential Drug Targets

Author(s): Daniel J. Ericsson, Alistair Standish, Bostjan Kobe, Renato Morona.

Journal Name: Current Drug Targets

Volume 13 , Issue 11 , 2012

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Abstract:

The bacterial capsule is a recognized virulence factor in pathogenic bacteria. It likely works as an antiphagocytic barrier by minimizing complement deposition on the bacterial surface. With the continual rise of bacterial pathogens resistant to multiple antibiotics, there is an increasing need for novel drugs. In the Wzy-dependent pathway, the biosynthesis of capsular polysaccharide (CPS) is regulated by a phosphoregulatory system, whose main components consist of bacterial-tyrosine kinases (BY-kinases) and their cognate phosphatases. The ability to regulate capsule biosynthesis has been shown to be vital for pathogenicity, because different stages of infection require a shift in capsule thickness, making the phosphoregulatory proteins suitable as drug targets. Here, we review the role of regulatory proteins focusing on Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli and discuss their suitability as targets in structure-based drug design.

Keywords: Antibiotic resistance, bacterial pathogens, capsule, drug discovery, protein tyrosine kinase, protein tyrosine phosphatase, Wzy, Bacterial Capsule, capsular polysaccharide (CPS), bacterial-tyrosine kinases (BY-kinases).

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Article Details

VOLUME: 13
ISSUE: 11
Year: 2012
Page: [1421 - 1431]
Pages: 11
DOI: 10.2174/138945012803530279
Price: $58

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