Type III secretion system needle protein PscF (PscF)

Type III secretion system needle protein PscF is the major structural subunit of the injection apparatus used by the Gram-negative pathogen Pseudomonas aeruginosa [1, 2]. This protein polymerizes to form a hollow needle that serves as a conduit for the delivery of effector toxins directly into the cytoplasm of host immune cells [1, 3]. The translocation of these toxins is a key virulence mechanism that allows the bacterium to subvert host defenses and cause severe tissue damage [3]. PscF is considered a high-priority anti-virulence target because its inhibition can disarm the pathogen without affecting its growth, potentially minimizing the development of antibiotic resistance [1, 4]. Small molecule inhibitors, such as the phenoxyacetamide series, have been shown to target PscF and block the assembly or function of the T3SS needle [1]. These inhibitors effectively prevent the secretion of toxins like ExoS and ExoU, thereby attenuating the pathogenicity of P. aeruginosa in infection models [1]. Targeting PscF is particularly relevant for treating chronic infections in cystic fibrosis patients and acute infections like ventilator-associated pneumonia [3]. Therapeutic challenges include the emergence of resistance mutations in the pscF gene and the need for effective delivery to the site of infection [1].

Other names

PscFT3SS needle proteinNeedle subunit protein PscFType III secretion needle protein

Inhibition of the Type III secretion system (T3SS) by binding to the PscF needle subunit, thereby preventing the assembly or function of the secretion needle and blocking the translocation of effector toxins into host cells [1].