Pathogenic Puppetry: Manipulation of the Host Actin Cytoskeleton by Chlamydia trachomatis

Abstract

The actin cytoskeleton is crucially important to maintenance of the cellular structure, cell motility, and endocytosis. Accordingly, bacterial pathogens often co-opt the actin-restructuring machinery of host cells to access or create a favorable environment for their own replication. The obligate intracellular organism Chlamydia trachomatis and related species exemplify this dynamic: by inducing actin polymerization at the site of pathogen-host attachment, Chlamydiae induce their own uptake by the typically non-phagocytic epithelium they infect. The interaction of chlamydial adhesins with host surface receptors has been implicated in this effect, as has the activity of the chlamydial effector TarP (translocated actin recruitment protein). Following invasion, C. trachomatis dynamically assembles and maintains an actin-rich cage around the pathogen's membrane-bound replicative niche, known as the chlamydial inclusion. Through further induction of actin polymerization and modulation of the actin-crosslinking protein myosin II, C. trachomatis promotes egress from the host via extrusion of the inclusion. In this review, we present the experimental findings that can inform our understanding of actin-dependent chlamydial pathogenesis, discuss lingering questions, and identify potential avenues of future study.Int. J. Mol. Sci. 2020, 21, 90 2 of 21 regulated by the Rho family GTPases RhoA-C, Rac1, and Cdc42-all of which are targets for modulation by pathogens seeking to restructure actin and thereby facilitate pathogenesis [6,7].The manipulation of host actin can promote a wide variety of beneficial outcomes for the pathogen. Salmonella spp. translocate the effectors SopE and SopE2 into host cells-these guanine exchange factor (GEF) mimics enhance the activity of Rac1 and Cdc42, creating localized concentrations of F-actin at the apical surface of mucosal epithelia [8][9][10][11]. The result is extensive ruffling of the plasma membrane at the site of Salmonella attachment, leading to internalization of the pathogen via micropinocytosis [8,[12][13][14]. Upon internalization and escape into the host cytosol, the Gram-positive intracellular pathogen Listeria monocytogenes induces the polymerization of actin on the bacterial surface through the activity of ActA, a surface protein functionally analogous to the nucleation promotion factor WASP [15]. ActA recruits an Arp2/3 complex to the bacterial pole, resulting in branched actin polymerization producing a comet-shaped structure that propels Listeria across the cytosol and into adjacent uninfected cells [16][17][18][19][20].Indeed, this dynamic can be observed even in non-invasive bacterial pathogens. Enteropathogenic and enterohemorrhagic E. coli (EPEC/EHEC) induce the formation of distinctive, actin-rich pedestals that facilitate their attachment to gastric epithelia. The virulence factor Tir is responsible for this effect: upon delivery into host cells by the E. coli type III secretion system (T3SS), Tir is incorporated into the plasma membrane, promoting EPEC/EHEC attachm...

The Chlamydia trachomatis secreted effector TmeA hijacks the N-WASP-ARP2/3 actin remodeling axis to facilitate cellular invasion

“…trachomatis EBs. Following invasion, TmeA could interact with AHNAK to undo the actin-bundling effects induced during the invasion process [ 40 ] ( Fig 8 ).…”

A glance on the role of actin in osteogenic and adipogenic differentiation of mesenchymal stem cells

“…There are various bacteria mentioned in Table 3 which induce polymerization [139,140]. Some bacteria, i.e., Escherichia coli, attach to the cell membrane by structuring specialized actin filaments [141], whereas others, i.e., Chlamydia, induce actin polymerization in host cells helping itself for its reproduction [143,144].…”

“… [ 141 , 142 ] Chlamydia trachomatis Secrete actin-recruiting phosphoprotein (Tarp) which cause actin polymerization depolymerization in the host cell. [ 143 , 144 ] Coxiella burnetii Infects phagocytic human macrophages via binding to complement receptor 3 (CR3) receptors, triggering the reorganization of filamentous actin at the attachment site. [ 145 ] Rickettsia conorii Attachment to host cell requires actin rearrangement via recruitment and activation of Arp2/3.…”

Insights into gene expression responses to infections in teleosts using microarray data: a systematic review

“…Additionally, reconfigurations and reorganizations of the host actin have been observed during cellular infections by pathogens that are unable to survive and replicate outside host cells, such as viruses and strictly intracellular bacteria or parasites (Elliott et al 2001;Radtke et al 2006;Bhavsar, Guttman & Finlay 2007;Fr enal & Soldati-Favre 2009;Taylor, Koyuncu & Enquist 2011). These pathogens are capable of extensively manipulating the host actin in order to facilitate host invasion, maintain their replicative niche and egress from host epithelial cells (Caven & Carabeo 2020).…”