RT Journal Article SR Electronic T1 The intracellular pathogen Francisella tularensis escapes from adaptive immunity by metabolic adaptation JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202201441 DO 10.26508/lsa.202201441 VO 5 IS 10 A1 Kensuke Shibata A1 Takashi Shimizu A1 Mashio Nakahara A1 Emi Ito A1 Francois Legoux A1 Shotaro Fujii A1 Yuka Yamada A1 Makoto Furutani-Seiki A1 Olivier Lantz A1 Sho Yamasaki A1 Masahisa Watarai A1 Mutsunori Shirai YR 2022 UL https://www.life-science-alliance.org/content/5/10/e202201441.abstract AB 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 ribDFT-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.