N JACQUIER¹, PH VIOLLIER², G GREUB<sup>1

1</sup>Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland, ²Department of Microbiology & Molecular Medicine, Institute of Genetics & Genomics in Geneva (iGE3), Faculty of Medicine / CMU, University of Geneva, Switzerland

Chlamydiales are obligate intracellular bacteria, such as Chlamydia trachomatis and Chlamydia pneumoniae, which are important human pathogens. All Chlamydiales share a common peculiar division mechanism, which is independent of the bacterial division organizer FtsZ, a bacterial homologue of tubulin, as an FtsZ-encoding sequence is absent from all the chlamydial genomes sequenced up to date. Nevertheless, Chlamydiales divide by binary fission in a process that highly resembles the peptidoglycan(cell wall)-driven constriction of other bacteria. Using the Chlamydia-related bacterium Waddlia chondrophila as a model, we recently provided pharmacological and cytological evidence for a role of the actin homologue MreB and its regulator RodZ in cell division of W. chondrophila (1). We could also show that the Pal-Tol complex involved in integrity maintenance of the link between the inner and the outer membrane is conserved in Chlamydiales and is highly enriched at the division septum (2). In this study, we further investigated the link between septum formation by RodZ and MreB and peptidoglycan synthesis and remodelling. For this purpose, we initiated several screens to find potential interactors of both RodZ and peptidoglycan. Using immunoprecipitation and mass spectrometry analysis, we could identify several candidates that are conserved in all Chlamydiales and that might play a role in the coordination of septum formation and peptidoglycan remodeling. We could confirm that some of these candidates (i) localize to the division septum, (ii) directly bind peptidoglycan and (iii) cause division defect when overexpressed in an E. coli system, highlighting their role in bacterial division. We need now to investigate if these proteins have a structural effect on peptidoglycan remodeling and how their recruitment to the division septum is regulated. These proteins can be potential targets for new antibiotics specifically targeting Chlamydiales, avoiding development of resistance in other bacteria.
1. Jacquier N, Frandi A, Pillonel T, Viollier PH, Greub G. Nat Commun. 2014 Apr 8;5:3578.
2. Jacquier N, Frandi A, Viollier PH, Greub G. Chem Biol. 2015 Sep 17;22(9):1217-27.