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 Shibata, Kensuke A1 Shimizu, Takashi A1 Nakahara, Mashio A1 Ito, Emi A1 Legoux, Francois A1 Fujii, Shotaro A1 Yamada, Yuka A1 Furutani-Seiki, Makoto A1 Lantz, Olivier A1 Yamasaki, Sho A1 Watarai, Masahisa A1 Shirai, Mutsunori YR 2022 UL http://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.