Biomaterial Database

The intracellular pathogen Francisella tularensis escapes from adaptive immunity by metabolic adaptation. 2022

Kensuke Shibata, and Takashi Shimizu, and Mashio Nakahara, and Emi Ito, and Francois Legoux, and Shotaro Fujii, and Yuka Yamada, and Makoto Furutani-Seiki, and Olivier Lantz, and Sho Yamasaki, and Masahisa Watarai, and Mutsunori Shirai

Department of Microbiology and Immunology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan kshibata@yamaguchi-u.ac.jp.

Intracellular pathogens lose many metabolic genes during their evolution from free-living bacteria, but the pathogenic consequences of their altered metabolic programs on host immunity are poorly understood. Here, we show that a pathogenic strain of Francisella tularensis subsp. tularensis (FT) has five amino acid substitutions in RibD, a converting enzyme of the riboflavin synthetic pathway responsible for generating metabolites recognized by mucosal-associated invariant T (MAIT) cells. Metabolites from a free-living strain, F. tularensis subsp. novicida (FN), activated MAIT cells in a T-cell receptor (TCR)-dependent manner, whereas introduction of FT-type ribD to the free-living strain was sufficient to attenuate this activation in both human and mouse MAIT cells. Intranasal infection in mice showed that the ribD FT-expressing FN strain induced impaired Th1-type MAIT cell expansion and resulted in reduced bacterial clearance and worsened survival compared with the wild-type free-living strain FN. These results demonstrate that F. tularensis can acquire immune evasion capacity by alteration of metabolic programs during evolution.

UI	MeSH Term	Description	Entries
D005603	Francisella	The lone genus of bacteria in the family Francisellaceae, frequently found in natural waters. It can be parasitic in humans, other MAMMALS; BIRDS; and ARTHROPODS.	Francisellaceae
D005604	Francisella tularensis	The etiologic agent of TULAREMIA in man and other warm-blooded animals.	Bacterium tularense,Brucella tularensis,Francisella tularense,Pasteurella tularensis
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D057131	Immune Evasion	Methods used by pathogenic organisms to evade a host's immune system.	Evasion, Immune,Evasions, Immune,Immune Evasions