Pathogenic bacteria are armed with potent effector proteins that subvert host signalling processes during infection1. The activities of bacterial effectors and their associated roles within the host cell are often poorly understood, particularly for Chlamydia trachomatis2, a World Health Organization designated neglected disease pathogen. We identify and explain remarkable dual Lys63-deubiquitinase (DUB) and Lys-acetyltransferase activities in the Chlamydia effector ChlaDUB1. Crystal structures capturing intermediate stages of each reaction reveal how the same catalytic centre of ChlaDUB1 can facilitate such distinct processes, and enable the generation of mutations that uncouple the two activities. Targeted Chlamydia mutant strains allow us to link the DUB activity of ChlaDUB1 and the related, dedicated DUB ChlaDUB2 to fragmentation of the host Golgi apparatus, a key process in Chlamydia infection for which effectors have remained elusive. Our work illustrates the incredible versatility of bacterial effector proteins, and provides important insights towards understanding Chlamydia pathogenesis.
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We thank members of our laboratories for reagents and advice, particularly Lee Dolat (Duke University) for his contribution to some preliminary Chlamydia infection work. Access to DLS was supported in part by the EU FP7 infrastructure grant BIOSTRUCT-X (contract no. 283570). Work in the D.K. lab was funded by the Medical Research Council (grant no. U105192732), the European Research Council (grant no. 724804), and the Lister Institute for Preventive Medicine. J.N.P. was supported on an EMBO Long-Term Fellowship. Work in the R.H.V. lab was funded by the National Institute of Health (grant no. R01AI100759 to R.H.V.) and the National Institute of Allergy and Infectious Diseases (grant no. STI CRC U19 AI084044 to R.J.B. and R.H.V.). E.B. was supported by North West Cancer Research. B.S. was supported by the Medical Research Council.
The authors declare no competing interests.
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Pruneda, J.N., Bastidas, R.J., Bertsoulaki, E. et al. A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation. Nat Microbiol 3, 1377–1384 (2018). https://doi.org/10.1038/s41564-018-0271-y
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