Francisella tularensis IglG Belongs to a Novel Family of PAAR-Like T6SS Proteins and Harbors a Unique N-terminal Extension Required for Virulence

PLoS Pathogens

Olivier Walker¹  Amandine Martin¹  Laurent Terradot¹  Mélanie Rigard¹  Maggy Hologne²  Wayne Conlan²  Philippe Telouk³  Claire Punginelli³  Amandine Mosnier³  Thomas Henry³  Claire Lays⁴  Alain Charbit⁵  Lena Lindgren⁵  Anders Sjöstedt⁵  Jeanette E. Bröms⁵ 

[1] CIRI, International Center for Infectiology Research, Inserm U1111, CNRS, UMR5308, Lyon, France;Department of Clinical Microbiology, Clinical Bacteriology, and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden;Ecole Normale Supérieure de Lyon, Lyon, France;Institut des Sciences Analytiques, CNRS, UMR 5280, Université de Lyon, Université Claude Bernard Lyon 1, ENS de Lyon, Villeurbanne, France;University of Lyon, Lyon, France

关键词: Francisella tularensis;    Cysteine;    Secretion;    Macrophages;    Francisella;    Secretion systems;    Protein secretion;    Zinc;   

DOI  :  10.1371/journal.ppat.1005821

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The virulence of Francisella tularensis, the etiological agent of tularemia, relies on an atypical type VI secretion system (T6SS) encoded by a genomic island termed the Francisella Pathogenicity Island (FPI). While the importance of the FPI in F. tularensis virulence is clearly established, the precise role of most of the FPI-encoded proteins remains to be deciphered. In this study, using highly virulent F. tularensis strains and the closely related species F. novicida, IglG was characterized as a protein featuring a unique α-helical N-terminal extension and a domain of unknown function (DUF4280), present in more than 250 bacterial species. Three dimensional modeling of IglG and of the DUF4280 consensus protein sequence indicates that these proteins adopt a PAAR-like fold, suggesting they could cap the T6SS in a similar way as the recently described PAAR proteins. The newly identified PAAR-like motif is characterized by four conserved cysteine residues, also present in IglG, which may bind a metal atom. We demonstrate that IglG binds metal ions and that each individual cysteine is required for T6SS-dependent secretion of IglG and of the Hcp homologue, IglC and for the F. novicida intracellular life cycle. In contrast, the Francisella-specific N-terminal α-helical extension is not required for IglG secretion, but is critical for F. novicida virulence and for the interaction of IglG with another FPI-encoded protein, IglF. Altogether, our data suggest that IglG is a PAAR-like protein acting as a bi-modal protein that may connect the tip of the Francisella T6SS with a putative T6SS effector, IglF.

【 授权许可】

CC BY