The Protease Locus of Francisella tularensis LVS Is Required for Stress Tolerance and Infection in the Mammalian Host

Infection and Immunity
Lihong HeJing-Ren Zhang

Abstract

Francisella tularensis is the causative agent of tularemia and a category A potential agent of bioterrorism, but the pathogenic mechanisms of F. tularensis are largely unknown. Our previous transposon mutagenesis screen identified 95 lung infectivity-associated F. tularensis genes, including those encoding the Lon and ClpP proteases. The present study validates the importance of Lon and ClpP in intramacrophage growth and infection of the mammalian host by using unmarked deletion mutants of the F. tularensis live vaccine strain (LVS). Further experiments revealed that lon and clpP are also required for F. tularensis tolerance to stressful conditions. A quantitative proteomic comparison between heat-stressed LVS and the isogenic Lon-deficient mutant identified 29 putative Lon substrate proteins. The follow-up protein degradation experiments identified five substrates of the F. tularensis Lon protease (FTL578, FTL663, FTL1217, FTL1228, and FTL1957). FTL578 (ornithine cyclodeaminase), FTL663 (heat shock protein), and FTL1228 (iron-sulfur activator complex subunit SufD) have been previously described as virulence-associated factors in F. tularensis Identification of these Lon substrates has thus provided important clues for further ...Continue Reading

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Citations

Nov 22, 2017·Journal of Bacteriology·Amy E RohlfingSimon L Dove
Jan 20, 2020·Molecular Microbiology·Charlotte MasonZhiming Ouyang
Jun 27, 2020·PLoS Genetics·Avatar JoshiFitnat H Yildiz
Aug 19, 2018·Emerging Microbes & Infections·Lihong HeJing-Ren Zhang
May 28, 2020·International Journal of Molecular Sciences·Donata FigajJoanna Skorko-Glonek

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