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Peptidoglycan hydrolase PcsB (PcsB) is a highly conserved enzyme essential for cell wall remodeling and daughter cell separation in Streptococcus pneumoniae and other streptococci. It contains a catalytic cysteine- and histidine-dependent aminohydrolase/peptidase (CHAP) domain and a regulatory coiled-coil domain that mediates auto-inhibition. PcsB is regulated by the WalRK (VicRK) two-component system and is activated through its interaction with the FtsEX cell division complex at the septum. Because of its essential role in bacterial viability and its high conservation across serotypes, PcsB is a prominent target for the development of novel antibiotics and vaccines. Inhibition or depletion of PcsB leads to severe defects in cell division, characterized by the formation of large cell clusters and increased sensitivity to osmotic stress and existing antibiotics. A trivalent vaccine candidate (IC47) containing recombinant PcsB has been evaluated in Phase 1 clinical trials and shown to be safe and immunogenic in humans.
Induction of protective antibodies and opsonophagocytic killing; potential inhibition of peptidoglycan hydrolysis and cell division
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