Implications of back-and-forth motion and powerful propulsion for spirochetal invasion

Abstract

the spirochete Leptospira spp. can move in liquid and on a solid surface using two periplasmic flagella (pfs), and its motility is an essential virulence factor for the pathogenic species. Mammals are infected with the spirochete through the wounded dermis, which implies the importance of behaviors on the boundary with such viscoelastic milieu; however, the leptospiral pathogenicity involving motility remains unclear. We used a glass chamber containing a gel area adjoining the leptospiral suspension to resemble host dermis exposed to contaminated water and analyzed the motility of individual cells at the liquid-gel border. insertion of one end of the cell body to the gel increased switching of the swimming direction. Moreover, the swimming force of Leptospira was also measured by trapping single cells using an optical tweezer. it was found that they can generate ∼ 17 pN of force, which is ∼ 30 times of the swimming force of Escherichia coli. the force-speed relationship suggested the loaddependent force enhancement and showed that the power (the work per unit time) for the propulsion is ∼ 3.1 × 10-16 W, which is two-order of magnitudes larger than the propulsive power of E. coli. the powerful and efficient propulsion of Leptospira using back-and-forth movements could facilitate their invasion. Motility has been identified as a crucial virulence factor for pathogenic bacteria 1. For example, a motility-deficient mutant of Vibrio cholerae is attenuated due to the decreased invasion efficiency of the epithelium 2. In some flagellated bacteria, both motility and flagella are considered essential as an adhesin. For example, Salmonella enterica attaches to the host tissue via peritrichous flagella, which results in colonization and clinical outcomes 3. Although spirochetes, such as Borrelia burgdorferi (the Lyme disease) 4 and Brachyspira hyodysenteriae (swine dysentery) 5 , also utilize motility during infection, their flagella exist beneath the outer membrane, which is known as the periplasmic flagella (PFs), and spirochetal flagella are not directly involved in pathogenicity. Instead, the improvement of swimming ability 6 and diverse adherence 7 in viscoelastic environments is believed to be responsible for their colonization and dissemination within hosts. The genus Leptospira is a member of spirochetes, and these pathogenic species have been found to cause a worldwide zoonosis known as leptospirosis. Pathogenic Leptospira cells are maintained in the proximal renal tubules of rodents as a reservoir. When the hosts urinate, they spread the spirochetes into the environment; as a result, many mammals, including humans, are percutaneously or transmucosally infected by contact with the contaminated soil and water 8,9. Leptospira spp. have a right-handed spiral cell body and exhibit curvatures at both ends (Fig. 1A). Spirochetes can swim in liquid and crawl on surfaces using two PFs (one PF/cell end) (Fig. 1B). The morphology of the cell ends frequently changes between a spiral and a hook shape; and there is an asymmetri...

Motility of the Zoonotic Spirochete Leptospira: Insight into Association with Pathogenicity

“…The enhancement of the motion-mode switching is observed in Ficoll, methylcellulose, and mucin solutions [16]. In addition, we revealed that the swimming direction reverses more frequently in high viscosity (Figure 2a) [16,20]. Enhancing "back and forth" movement suggests the limitation of the net migration, crowding bacteria within the mucus layer, and facilitating colonization over the tissues (Figure 2b).…”

“…Leptospira switches swimming direction within <1 s [20]. Such a quick reversal suggests the coordination between two PFs mediated by unidentified signal transduction, but there is no definitive evidence so far.…”

“…However, in gel-like viscoelastic fluids (e.g., methylcellulose solution), the motion efficiency of Leptospira is improved up to 100% [15], resulting in an increment of the swimming velocity [19]. Interestingly, the addition of viscous agent to medium increases the frequency of swimming reversal, as discussed later [16,20].…”

Disassembly of the apical junctional complex during the transmigration of Leptospira interrogans across polarized renal proximal tubule epithelial cells

“…However, we could not rule out the role of other Rho regulatory proteins such as p120‐catenin which is altered in L. interrogans ‐ infected RPTECs (Schackmann, Tenhagen, van de Ven, & Derksen, 2013 ) (Figure 8 ). Moreover, the tight interactions of L. interrogans with the plasma membrane and efficient propulsion of L. interrogans using back ‐and forth movements can facilitate their invasion through AJCs and apply an additional mechanical force to enhance AJC disassembly (Abe, Kuribayashi, Takabe, & Nakamura, 2020 ).…”

Pathogenesis insights from an ancient and ubiquitous spirochete

“…Leptospires are unique in that they have a single supercoiled endoflagellum extending axially toward the middle of the cell from a flagellar motor embedded in the inner membrane at each pole, without overlap. Endoflagellar rotation imparts a swimming motility that enables leptospires to be particularly invasive at liquid–gel borders, such as the interface between the vascular lumen and the endothelium, with 30 times the swimming force of Escherichia coli [ 16 ]. Recent elegant high-resolution cryo-electronic tomography studies have shown that the function of leptospiral endoflagellar filaments relies on an asymmetric sheath that imparts their supercoiled structure [ 17 ].…”