Biology subjects

Sixt, B. S.

Publications and source records attributed to Sixt, B. S..

3 recordsLinked to original sources

bioRxiv2023

The acetylase activity of Cdu1 protects Chlamydia effectors from degradation to regulate bacterial exit from infected cells

Many cellular processes are regulated by ubiquitin-mediated proteasomal degradation. Pathogens can regulate eukaryotic proteolysis through the delivery of proteins with de-ubiquitinating (DUB) activities. The obligate intracellular pathogen Chlamydia trachomatis secretes Cdu1 (ChlaDUB1), a dual deubiquitinase and Lys-acetyltransferase, that promotes Golgi remodeling and survival of infected host cells presumably by regulating the ubiquitination of host and bacterial proteins. Here we determined that Cdu1s acetylase but not its DUB activity is important to protect Cdu1 from ubiquitin-mediated degradation. We further identified three C. trachomatis proteins on the pathogen-containing vacuole (InaC, IpaM, and CTL0480) that required Cdu1 s acetylase activity for protection from degradation and determined that Cdu1 and these Cdu1-protected proteins are required for optimal egress of Chlamydia from host cells. These findings highlight a non-canonical mechanism of pathogen-mediated protection of virulence factors from degradation after their delivery into host cells and the coordinated regulation of secreted effector proteins.

microbiology↗

bioRxiv2022

Ecology and evolution of chlamydial symbionts of arthropods

The phylum Chlamydiae consists of obligate intracellular bacteria including major human pathogens and diverse environmental representatives. Here we investigated the Rhabdochlamydiaceae, which is predicted to be the largest and most diverse chlamydial family, with the few described members known to infect arthropod hosts. Using published 16S rRNA gene sequence data we identified at least 388 genus-level lineages containing about 14 051 putative species within this family. We show that rhabdochlamydiae are mainly found in freshwater and soil environments, suggesting the existence of diverse, yet unknown hosts. Next, we used a comprehensive genome dataset including metagenome assembled genomes classified as members of the family Rhabdochlamydiaceae, and we added novel complete genome sequences of Rhabdochlamydia porcellionis infecting the woodlouse Porcellio scaber, and of Candidatus R. oedothoracis associated with the linyphiid dwarf spider Oedothorax gibbosus. Comparative analysis of basic genome features and gene content with reference genomes of well-studied chlamydial families with known host ranges, namely Parachlamydiaceae (protist hosts) and Chlamydiaceae (human and other vertebrate hosts) suggested distinct niches for members of the Rhabdochlamydiaceae. We propose that members of the family represent intermediate stages of adaptation of chlamydiae from protists to vertebrate hosts. Within the genus Rhabdochlamydia, pronounced genome size reduction could be observed (1.49-1.93 Mb). The abundance and genomic distribution of transposases suggests transposable element expansion and subsequent gene inactivation as a mechanism of genome streamlining during adaptation to new hosts. This type of genome reduction has never been described before for any member of the phylum Chlamydiae. This study provides new insights into the molecular ecology, genomic diversity, and evolution of representatives of one of the most divergent chlamydial families.

genomics↗

bioRxiv2022

The Chlamydia protein CpoS modulates the inclusion microenvironment and restricts the interferon response by acting on Rab35

The obligate intracellular bacterium Chlamydia trachomatis inserts into the membrane of its vacuole (the inclusion) a family of poorly characterized Inc proteins. While the Inc CpoS was recently revealed as a critical suppressor of host cellular immune surveillance, the underlying mechanism remained unknown. By complementing a cpoS mutant with modified variants of CpoS, we found that CpoS blocks distinct cellular defense responses through distinct mechanisms. Specifically, we show that the ability of CpoS to interact with Rab GTPases is not only instrumental to its ability to mediate lipid transport to the inclusion, but also key to CpoS-mediated inhibition of type I interferon responses. Indeed, depletion of Rab35 can phenocopy the respective defect of the cpoS mutant. Unexpectedly, we found that CpoS is also essential for the formation of inclusion microdomains that control the spatial organization of multiple Incs involved in signaling and modulation of the host cellular cytoskeleton. Overall, our findings highlight the modulation of membrane trafficking as a pathogenic immune evasion strategy and the role of Inc-Inc interactions in shaping the inclusion microenvironment.

microbiology↗