A novel flagellar sheath protein, FcpA, determines filament coiling, translational motility and virulence for the Leptospira spirochete

Abstract

Summary Leptospira are unique among bacteria based on their helical cell morphology with hook-shaped ends and the presence of periplasmic flagella (PF) with pronounced spontaneous supercoiling. The factors that provoke such supercoiling, as well as the role that PF coiling plays in generating the characteristic hook-end cell morphology and motility, have not been elucidated. We have now identified an abundant protein from the pathogen L. interrogans, exposed on the PF surface, and named it Flagellar-coiling protein A (FcpA). The gene encoding FcpA is highly conserved among Leptospira and was not found in other bacteria. fcpA- mutants, obtained from clinical isolates or by allelic exchange, had relatively straight, smaller-diameter PF, and were not able to produce translational motility. These mutants lost their ability to cause disease in the standard hamster model of leptospirosis. Complementation of fcpA restored the wild-type morphology, motility and virulence phenotypes. In summary, we identified a novel Leptospira 36-kDa protein, the main component of the spirochete's PF sheath, and a key determinant of the flagella's coiled structure. FcpA is essential for bacterial translational motility and to enable the spirochete to penetrate the host, traverse tissue barriers, disseminate to cause systemic infection, and reach target organs.

Pathogenic <i>Leptospira</i>: Advances in understanding the molecular pathogenesis and virulence

“…However, addition of a viable FcpA to complement the mutant was shown to restore the morphology of the wild-type species as well as the phenotypes for motility and virulence (Wunder et al, 2016). These studies suggest a central role of the FcpA protein in the ability of the bacteria to translocate, infiltrate the host, cross tissue barriers to target organs and cause systemic infections (Wunder et al, 2016). Overall, these studies show that the morphological orientation of the flagella coiling protein modulates Leptospira infectivity.…”

“…The cell morphology of Leptospira is determined by the layers of the cytoskeleton and murein proteins (Slamti et al, 2011) and confirmed by cryo-electron tomographical techniques (Raddi et al, 2012). A recent study identified a novel 36-kDa Leptospira protein, shown to be the main component of the spirochete's periplasmic flagella (PF) sheath (Wunder et al, 2016). This protein, named the Flagellar-coiling protein A (FcpA), was shown to determine the coiled structure of the bacterial flagella and appeared to be an abundant protein on the L. interrogans PF surface (Wunder et al, 2016).…”

“…Analysis of the (FcpA(-)) mutants generated for the FcpA showed loss of potential to cause leptospirosis in animal models. However, addition of a viable FcpA to complement the mutant was shown to restore the morphology of the wild-type species as well as the phenotypes for motility and virulence (Wunder et al, 2016). These studies suggest a central role of the FcpA protein in the ability of the bacteria to translocate, infiltrate the host, cross tissue barriers to target organs and cause systemic infections (Wunder et al, 2016).…”

“…A recent study identified a novel 36-kDa Leptospira protein, shown to be the main component of the spirochete's periplasmic flagella (PF) sheath (Wunder et al, 2016). This protein, named the Flagellar-coiling protein A (FcpA), was shown to determine the coiled structure of the bacterial flagella and appeared to be an abundant protein on the L. interrogans PF surface (Wunder et al, 2016). Additional analysis of the gene that codes for the FcpA protein revealed a highly conserved consensus region among Leptospira, a characteristic that was not seen in other bacteria (Wunder et al, 2016).…”

“…This protein, named the Flagellar-coiling protein A (FcpA), was shown to determine the coiled structure of the bacterial flagella and appeared to be an abundant protein on the L. interrogans PF surface (Wunder et al, 2016). Additional analysis of the gene that codes for the FcpA protein revealed a highly conserved consensus region among Leptospira, a characteristic that was not seen in other bacteria (Wunder et al, 2016). Analysis of the (FcpA(-)) mutants generated for the FcpA showed loss of potential to cause leptospirosis in animal models.…”