2022/06/06 by Kensuke Shibata, Takashi Shimizu, Mashio Nakahara +9 · 1 citation
Biochemistry, Genetics and Molecular Biology · Medicine · #Vibrio bacteria research studies #Viral gastroenteritis research and epidemiology #Bacillus and Francisella bacterial research
paper · pdf · doi:10.26508/lsa.202201441
openalex publication_date 2022/06/06 · openalex created_date 2022/06/13 · openalex updated_date 2026/07/22
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.