The chlamydial OTU domain-containing proteinChlaOTU is an early type III secretion effector targeting ubiquitin and NDP52

Abstract

SummaryChlamydia are obligate intracellular pathogens. Upon contact with the host, they use type III secretion to deliver proteins into the cell, thereby triggering actin-dependent entry and establishing the infection. We observed that Chlamydia caviae elicited a local and transient accumulation of ubiquitinated proteins at the entry sites, which disappeared within 20 min. We investigated the mechanism for the rapid clearance of ubiquitin. We showed that the OTU-like domain containing protein CCA00261, predicted to have deubiquitinase activity, was detected in infectious particles and was a type III secretion effector. This protein is present in several Chlamydia strains, including the human pathogen Chlamydia pneumoniae, and we further designate it as ChlaOTU. We demonstrated that ChlaOTU bound ubiquitin and NDP52, and we mapped these interactions to distinct domains. NDP52 was recruited to Chlamydia entry sites and was dispensable for infection and for bacterial growth. ChlaOTU functioned as a deubiquitinase in vitro. Heterologous expression of ChlaOTU reduced ubiquitin accumulation at the entry sites, while a catalytic mutant of the deubiquitinase activity had the opposite effect. Altogether, we have identified a novel secreted protein of chlamydiae. ChlaOTU targets both ubiquitin and NDP52 and likely participates in the clearance of ubiquitin at the invasion sites.

Recent genome reduction ofWolbachiainDrosophila recenstargets phage WO and narrows candidates for reproductive parasitism

“…Indeed, wsp is known to be involved in pathogenicity and host interaction (Uday & Puttaraju, 2012) while OTU-like cysteine proteases have deubiquitinase activity facilitating the pathogenicity of intracellular pathogens and viruses (Furtado et al, 2013; Makarova, Aravind & Koonin, 2000). Although the function of the hypothetical proteins is unknown, the presence of transmembrane (TM) domains suggests interaction with the bacterial membrane and potentially its Drosophila host.…”

Chlamydia cell biology and pathogenesis

“…Chlamydia spp. secrete T3SS effectors that modulate host ubiquitylation and protein stability, including the deubiquitinase Cpn0483 (also known as Chla OTU) produced by C. pneumoniae 139 and the deubiquitinases ChlaDub1 and ChlaDub2 (also known as CT867) produced by C. trachomatis 140,141 . Furthermore, Incs that are produced by C. trachomatis may interact with the host ubiquitylation machinery 67 , which reveals additional routes to target protein stability.…”

Modulation of host signaling and cellular responses by Chlamydia

“…Tarp and CT694, two of these effectors involved in actin modulation have been discussed in the previous section. A recent report describes ChlaOTU as another early effector with deubiquitinating activity [84]. Formation of endosomes with C. caviae is accompanied by extensive ubiquitination, which is likely removed through the action of ChlaOTU.…”

“…Formation of endosomes with C. caviae is accompanied by extensive ubiquitination, which is likely removed through the action of ChlaOTU. Interaction between ChlaOTU and host autophagy receptor NDP52 has been observed but appears to be dispensable for infection [84]. ChlaOTU is well conserved in C. pneumoniae but homology in C. trachomatis and C. muridarum is weak [84].…”

“…Interaction between ChlaOTU and host autophagy receptor NDP52 has been observed but appears to be dispensable for infection [84]. ChlaOTU is well conserved in C. pneumoniae but homology in C. trachomatis and C. muridarum is weak [84]. Transport of early inclusions of C. trachomatis and C. pneumoniae proceeds in a microtubule and Src family kinase dependent manner resulting in transport to the microtubule organizing center (MTOC) [85-87].…”