Chlamydia trachomatisinfection prevents front-rear polarity of migrating HeLa cells

Abstract

SummaryChlamydiae are obligate intracellular bacterial pathogens that cause trachoma, sexually transmitted diseases and respiratory infections in humans. Fragmentation of the host cell Golgi apparatus (GA) is essential for chlamydial development, whereas the consequences for host cell functions, including cell migration are not well understood. We could show that Chlamydia trachomatisinfected cells display decelerated migration and fail to repopulate monolayer scratch wounds. Furthermore, infected cells lost the ability to reorient the fragmented GA or the microtubule organization centre (MTOC) after a migratory stimulus. Silencing of golgin-84 phenocopied this defect in the absence of the infection. Interestingly, GA stabilization via knockdown of Rab6A and Rab11A improved its reorientation in infected cells and it was fully rescued after inhibition of Golgi fragmentation with WEHD-fmk. These results show that C. trachomatis infection perturbs host cell migration on multiple levels, including the alignment of GA and MTOC.

Icm/Dot-dependent inhibition of phagocyte migration byLegionellais antagonized by a translocated Ran GTPase activator

“…Finally, obligate intracellular bacteria of the genus Chlamydia also modulate cell migration. Whereas C. trachomatis was found to inhibit the non-directed migration of HeLa cells (Heymann et al, 2013), C. pneumoniae promotes cell adhesion and migration of vascular smooth muscle cells (Zhang et al, 2012), and endosymbiotic environmental Chlamydia control the motility of host Acanthamoeba (Okude et al, 2012).…”

“…In vitro scratch assays were performed essentially as described (Liang et al, 2007;Heymann et al, 2013). RAW 264.7 macrophages, A549 or HeLa cells were seeded into 35 mm μ-Dishes (Ibidi) at a density of 1.5 × 10 5 cells ml −1 (3 × 10 5 cells/ dish) and incubated for 24 h to reach confluency.…”

“…In the course of these studies we observed that not only LCV motility within phagocytes, but also phagocyte motility per se appeared to be controlled by LegG1. This observation, together with the fact that modulation of cell migration is a common theme among pathogenic bacteria utilizing a T3SS (Aepfelbacher et al ., ; McLaughlin et al ., ; Konradt et al ., ; Heymann et al ., ), prompted us to investigate in detail the modulation of cell migration by L. pneumophila and Icm/Dot‐translocated effectors. Here we show that L. pneumophila inhibits in a dose‐ and T4SS‐dependent manner the migration and chemotaxis of D. discoideum amoebae, macrophages and polymorphonuclear neutrophils (PMN).…”

The Chlamydia type III effector TarP alters the dynamics and organization of host cell focal adhesions

“…Previous works by Kumar and Valdivia (2008) and Heymann et al ., (2013) described the loss of motility of Chlamydia -infected epithelial cells. Heymann et al ., (2013) attributed this to the chlamydial inhibition of Golgi polarization that occurs at >24 h post-infection, leading to loss of directional migration.…”

“…Previous works by Kumar and Valdivia (2008) and Heymann et al ., (2013) described the loss of motility of Chlamydia -infected epithelial cells. Heymann et al ., (2013) attributed this to the chlamydial inhibition of Golgi polarization that occurs at >24 h post-infection, leading to loss of directional migration. In this report, we offer an alternate and possibly complementary mechanism of FA stabilization, which could lead to an increase of host-cell adhesion to the extracellular matrix (ECM), thus culminating in previously reported loss of motility (Kumar and Valdivia, 2008; Heymann et al ., 2013).…”