Chlamydia trachomatis TmeB antagonizes actin polymerization via direct interference with Arp2/3 activity

Abstract

Chlamydia trachomatis is an obligate intracellular pathogen that actively promotes invasion of epithelial cells. A virulence-associated type III secretion system contributes to chlamydial entry and at least four effectors have been described that are deployed during this time. Two of these invasion-related effectors, the translocated membrane-associated effectors A and B (TmeA and TmeB), are encoded in a bi-cistronic operon. TmeA directly activates host N-WASP to stimulate Arp2/3-dependent actin polymerization. According to current working models, TmeA-mediated N-WASP activation contributes to invasion. TmeB has not been functionally characterized. Unlike a tmeA null strain, loss of tmeB does not impact invasion efficiency of C. trachomatis. Using strains deficient for multiple genes, we provide evidence that TmeA is dispensable for invasion in the absence of TmeB. Our data indicate that overabundance of TmeB interferes with invasion and that this activity requires active Arp2/3 complex. We further show that TmeB is capable of interfering with Arp2/3-mediated actin polymerization. In aggregate, these data point to opposing functions for TmeA and TmeB that manifest during the invasion process. These studies raise intriguing questions regarding the dynamic interplay between TmeA, TmeB, and branched actin polymerization during chlamydial entry.

Global mapping of theChlamydia trachomatisconventional secreted effector – host interactome reveals CebN interacts with nucleoporins and Rae1 to impede STAT1 nuclear translocation

“…In our study, we sought to define PPIs for all the previously uncharacterized cT3SS effector proteins and included CT695 (TmeB) as at the onset of this study TmeB had no function ascribed to it. Recent work has since shown that ectopically expressed TmeB targets the ARP2/3 complex 71 . While we did not find components of the ARP2/3 complex in our infection AP-MS, we did identify an actin-binding protein, inverted formin 2 (INF2).…”

Dynamin-dependent entry of Chlamydia trachomatis is sequentially regulated by the effectors TarP and TmeA

“…As such, the interaction between N-WASP and SNX9 might explain Dyn2-dependence toward TmeA signaling. Intriguingly, TmeA also bears similarity with the C. pneumonaie secreted effector SemD 49 , 50 , which recruits the BAR-domain proteins PACSIN and SNX9 to induce membrane curvature and promote pathogen engulfment. On this basis, TmeA-mediated Dyn2 regulation could manifest via the formation of SNX9/Dyn2 heterodimers, providing a mechanism of Dyn2 modulation distinct from actin remodeling.…”