Zinc Acquisition Mechanisms Differ between Environmental and Virulent Francisella Species.

Zinc is an essential nutrient for bacterial growth. Because host cells can restrict pathogen access to zinc as an antimicrobial defense mechanism, intracellular pathogens such as must sense their environment and acquire zinc in response. In many bacteria, the conserved transcription factor Zur is a key regulator of zinc acquisition. To identify mechanisms of zinc uptake in U112, transcriptome sequencing of wild-type and putative mutant bacteria was performed. Only three genes were confirmed as directly regulated by Zur and zinc limitation by quantitative reverse transcription-PCR. One of these genes, FTN_0879, is predicted to encode a protein with similarity to the family of zinc transporters, which are not typically regulated by Zur. While a putative operon encoding a high-affinity zinc transporter was identified in U112, expression of this operon was not controlled by Zur or zinc concentration. Disruption of but not in U112 impaired growth under zinc limitation, suggesting that ZupT is the primary mechanism of zinc acquisition under these conditions. In the virulent subsp. Schu S4 strain, is a pseudogene, and attempts to delete were unsuccessful, suggesting that it is essential in this strain. A reverse TetR repression system was used to knock down the expression of in Schu S4, revealing that is required for growth under zinc limitation and contributes to intracellular growth within macrophages. Overall, this work identifies genes necessary for adaptation to zinc limitation and highlights nutritional differences between environmental and virulent strains. is a tier 1 select agent with a high potential for lethality and no approved vaccine. A better understanding of virulence factors is required for the development of therapeutics. While acquisition of zinc has been shown to be required for the virulence of numerous intracellular pathogens, zinc uptake has not been characterized in This work characterizes the Zur regulon in and identifies two transporters that contribute to bacterial growth under zinc limitation. In addition, these data identify differences in mechanisms of zinc uptake and tolerance to zinc limitation between and , highlighting the role of in the growth of Schu S4 under zinc limitation.