Host cyclophilin-mediated maturation of an obligate intracellular bacterial surface virulence factor.

ABSTRACT: Obligate intracellular bacterial pathogens cannot grow extracellularly, a trait that renders them highly understudied, but also endows them with unexpected host dependencies. Here, using the emerging obligate intracellular tickborne pathogen Rickettsia parkeri, we conducted a genome-scale CRISPR/Cas12a knockout infection screen to identify human cell determinants of rickettsial intracellular fitness. We discovered that the host peptidylprolyl isomerase cyclophilin A (PPIA/CypA), was essential for the formation of the R. parkeri actin tails that enable pathogen motility. PPIA localized to actin-associated bacterial poles and directly interacted with Sca2, the R. parkeri surface-exposed autotransporter chiefly responsible for actin tail nucleation. Sca2 bound PPIA throug

SUBMITTER: Sit B 

PROVIDER: S-EPMC12636401 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature