The N. gonorrhoeae Type IV Pilus Stimulates Mechanosensitive Pathways and Cytoprotection through a pilT-Dependent Mechanism

Abstract

The Neisseria gonorrhoeae type IV pilus is a retractile appendage that can generate forces near 100 pN. We tested the hypothesis that type IV pilus retraction influences epithelial cell gene expression by exerting tension on the host membrane. Wild-type and retraction-defective bacteria altered the expression of an identical set of epithelial cell genes during attachment. Interestingly, pilus retraction, per se, did not regulate novel gene expression but, rather, enhanced the expression of a subset of the infection-regulated genes. This is accomplished through mitogen-activated protein kinase activation and at least one other undefined stress-activated pathway. These results can be reproduced by applying artificial force on the epithelial membrane, using a magnet and magnetic beads. Importantly, this retraction-mediated signaling increases the ability of the cell to withstand apoptotic signals triggered by infection. We conclude that pilus retraction stimulates mechanosensitive pathways that enhance the expression of stress-responsive genes and activate cytoprotective signaling. A model for the role of pilus retraction in influencing host cell survival is presented.

3D structure/function analysis of PilX reveals how minor pilins can modulate the virulence properties of type IV pili

“…Whatever aspect of Tfp biology is to be studied, pilus retraction must be taken into account because it generates remarkable mechanical forces (25), likely promoted by domain movements within PilT (26). PilT-powered retraction is indispensable for intimate adhesion (27,28), twitching motility (7,8), competence for DNA transformation (29) and signaling to host cells (30), yet it must be counteracted to achieve efficient biogenesis of pilus filaments. Accordingly, almost half of the 15 proteins essential for Tfp biogenesis in N. meningitidis are required to stabilize the fibers by counterbalancing the action of PilT (31).…”

Influence of type IV pilus retraction on the architecture of the Neisseria gonorrhoeae-infected cell cortex

“…Tfp retraction from bacteria in a microcolony allows the community to crawl over the epithelial cell surface and fuse with other microcolonies to form larger motile structures (Higashi et al, 2007 Tfp retraction affects the infected epithelial cell at multiple levels. Retraction forces regulate epithelial gene expression and activate cytoprotective signalling pathways (Howie et al, 2005(Howie et al, , 2008Lee et al, 2005). Tfp retraction recruits host cell components to the cortex beneath adhered microcolonies.…”

Is it feasible to control pathogen infection by competitive binding of probiotics to the host?

“…5,6,7 Historically, such bacterial filaments have been well studied on pathogens who use different types of pilus, such as chaperone-usher pili, 8 curli pili, 9 and type IV pili 10 to attach onto the hosts from the "safe" distance circumventing their defense system. In fact, the binding of pilus proteins to the host cell receptors elicits different responses, leading to cytoprotection and remodeling of the host cells, 11,12 inflammation, 13 and internalization of the bacteria. 14 The sortasedependent pili, which had been previously dedicated to pathogenic Gram-positive bacteria, e.g., Actinomyces,…”