Identification of homologs of the Chlamydia trachomatis effector CteG reveals a family of Chlamydiaceae type III secreted proteins that can be delivered into host cells

Funding Information: We are grateful to Mariana Mend\u00E3o for the construction of plasmids, and to our colleagues Agathe Subtil, Ian Clarke, Mar\u00EDa Rosa Vergara, and Nicole Borel for generously providing DNA of several Chlamydia species and antibodies. Funding Information: This work was supported by Funda\u00E7\u00E3o para a Ci\u00EAncia e Tecnologia (FCT) through grant PTDC/BIA-MIC/28503/2017, and in the scope of the projects UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences \u2013 UCIBIO, and LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB. ISP and MPL were supported by PhD fellowships SFRH/BD/129756/2017 and SFRH/BD/144284/2019, respectively, also funded by FCT. Open access funding provided by FCT|FCCN (b-on) Publisher Copyright: © The Author(s) 2024. ; Chlamydiae are a large group of obligate endosymbionts of eukaryotes that includes the Chlamydiaceae family, comprising several animal pathogens. Among Chlamydiaceae, Chlamydia trachomatis causes widespread ocular and urogenital infections in humans. Like many bacterial pathogens, all Chlamydiae manipulate host cells by injecting them with type III secretion effector proteins. We previously characterized the C. trachomatis effector CteG, which localizes at the host cell Golgi and plasma membrane during distinct phases of the chlamydial infectious cycle. Here, we show that CteG is a Chlamydiaceae-specific effector with over 60 homologs phylogenetically categorized into two distinct clades (CteG I and CteG II) and exhibiting several inparalogs and outparalogs. Notably, cteG I homologs are syntenic to C. trachomatis cteG, whereas cteG II homologs are syntenic among themselves but not with C. trachomatis cteG. This indicates a complex evolution of cteG homologs, which is unique among C. trachomatis effectors, marked by numerous events of gene duplication and loss. Despite relatively modest sequence conservation, nearly all tested CteG I and CteG II proteins were identified as type ...