Title:Wzy-Dependent Bacterial Capsules as Potential Drug Targets
Volume: 13
Issue: 11
Author(s): Daniel J. Ericsson, Alistair Standish, Bostjan Kobe and Renato Morona
Affiliation:
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).
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.