Role of the Campylobacter jejuni Type VI secretion system and in silico identification of putative T6SS effectors

Abstract P11

Presenter: Janie Liaw (London School of Hygiene and Tropical Medicine)

Authors: Janie Liaw (1), Zahra Omole (1), Geunhye Hong (1), Cadi Davies (1), Nicolae Corcionivoschi (2), Abderrahman Hachani (3), Brendan Wren (1), Nick Dorrell (1), Ozan Gundogdu (1)

• 1 Department of Infection Biology, London School of Hygiene & Tropical Medicine, London, United Kingdom
• 2 Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Belfast, United Kingdom
• 3 The Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia

The Type VI Secretion System (T6SS), present in over 25% of gram-negative bacteria, is a contractile secretion nanomachine that injects effector proteins into bacterial or eukaryotic cells. In addition to killing or reducing the fitness of their microbial competitors, the T6SS can also subvert host cell processes by manipulating the host cytoskeleton, evading host defence mechanisms, and modulating host inflammatory responses. However, knowledge of the role of the T6SS in Campylobacter jejuni and identity of its secreted effectors remain limited despite a recent rise in the prevalence of the T6SS in C. jejuni isolates in humans and chickens. To investigate the role of the C. jejuni T6SS, the whole genome sequence of a novel human isolate 488 was compared with previously sequenced strains and a T6SS cluster was identified to be highly conserved and syntenic between human and chicken isolates. The presence of a functional T6SS in C. jejuni was demonstrated by expression of the T6SS genes and secretion of TssD (Hcp). Increased oxidative stress resistance in the 488 wild-type strain compared to a 488 tssD mutant indicated that the T6SS is associated with the oxidative stress response in C. jejuni. Presence of the T6SS also increased C. jejuni cytotoxicity in a Galleria mellonella infection model. In addition, the T6SS enhanced C. jejuni interaction and invasion of chicken primary intestinal cells and also enhanced the ability of C. jejuni to colonise chickens in a chick infection model. To further gain an understanding into the genetic architecture of the T6SS in C. jejuni, a comprehensive bioinformatic analysis of the C. jejuni T6SS was performed using publicly available genomes. In combination with analysis of the T6SS secretome, this led to the identification of a second canonical VgrG and a number of putative effectors downstream of the T6SS operon. These studies highlight the importance of the T6SS during in vivo survival of C. jejuni and also provide a framework for our current characterisation of C. jejuni T6SS effectors.

Presenting in Speaking session 2 - Pathogenesis