Type III secretion system needle tip protein PcrV (PcrV)

The Type III secretion system needle tip protein PcrV is a critical virulence factor found in Pseudomonas aeruginosa, an opportunistic pathogen frequently associated with healthcare-related infections. PcrV is localized at the distal tip of the bacterial Type III secretion system (T3SS) needle, where it acts as a scaffold for the assembly of the translocon pore, composed of the proteins PopB and PopD, within the host cell membrane (UniProt: P72170). This structural assembly is essential for the direct translocation of potent effector toxins, such as ExoS and ExoU, into the host cytoplasm, leading to cellular damage and evasion of the host immune system (Sawa et al., 1999). Due to its external location and high level of conservation across clinical strains, PcrV is a prominent target for passive immunization strategies using monoclonal antibodies. Therapeutic candidates like Gremubamab and KB001-A aim to neutralize PcrV, thereby preventing toxin delivery and attenuating the severity of pneumonia and other invasive P. aeruginosa infections (ClinicalTrials.gov: NCT02696031). This anti-virulence approach provides a potential alternative or adjunct to traditional antibiotics by disarming the pathogen without directly inducing bactericidal selective pressure.

Other names

PcrVType III secretion protein PcrVV-antigen homologLow calcium response protein VPseudomonas aeruginosa PcrV

Binding to the PcrV protein at the apex of the T3SS needle prevents the assembly of the translocon pore (PopB/PopD) in the host cell membrane, thereby blocking the injection of cytotoxic effector proteins into host cells (Sawa et al., 1999; DiGiandomenico et al., 2014).