Abstract
Regulation of gene transcription is the initial step in the complex process that controls gene expression within bacteria. Transcriptional control involves the joint effort of RNA polymerases and numerous other regulatory factors. Whether global or local, positive or negative, regulators play an essential role in the bacterial cell. For instance, some regulators specifically modify the transcription of virulence genes, thereby being indispensable to pathogenic bacteria. Here, we provide a comprehensive overview of important transcription factors and DNA-binding proteins described for the virulent bacterium Francisella tularensis, the causative agent of tularemia. This is an unexplored research area, and the poorly described networks of transcription factors merit additional experimental studies to help elucidate the molecular mechanisms of pathogenesis in this bacterium, and how they contribute to disease.
Highlights
Francisella tularensis belongs to the genus Francisella, which is highly diverse comprising a considerable number of species, and the genus is rapidly expanding
We provide a comprehensive overview of important transcription factors and DNA-binding proteins described for the virulent bacterium Francisella tularensis, the causative agent of tularemia
F. novicida is usually described as separate species, it shares >97% nucleotide identity with F. tularensis, the former is a rare human pathogen often derived from environmental sources [1]
Summary
Francisella tularensis belongs to the genus Francisella, which is highly diverse comprising a considerable number of species, and the genus is rapidly expanding. F. tularensis is a highly infectious human pathogen causing tularemia [2,3] It is an intracellular pathogen, the virulence of which is based on the ability to escape from phagosomes and replicate in the cytosol of the host cell. The most important virulence factors of F. tularensis include the capsule [11,12] and surface lipopolysaccharide layer [13,14,15,16]; membrane vesicles [6,17,18]; and secretion systems, especially the Type VI Secretion System (T6SS) [19,20,21,22] The latter is composed of proteins encoded by genes from the Francisella pathogenicity island (FPI) (pdpABCDE, iglABCDEFGHIJ, vgrG, DotU domain-containing protein (dotU)) [20,23,24]. Reference mglA sspA pigR hupB hfq iclR oxyR araC fur rpoA1 rpoA2 rpoB rpoC rpoZ rpoD rpoH pmrA/qseB kdpE bfpR interacting with SspA, regulation of FPI genes, necessary for intracellular replication interacting with MglA, regulation of FPI genes, necessary for stress response interacting with MglA/SspA, regulation of FPI genes global regulator, DNA non-specific binding protein RNA-binding protein, necessary for stress response, negative regulator of pdp operon important only for F. novicida virulence in vivo regulation of genes involved in oxidative stress response global regulator, active during oxidative stress conditions, regulation of some FPI genes and tricarboxylic acid (TCA) cycle during oxidative stress regulation of iron concentration RNAP subunit A1, gene transcription RNAP subunit A2, gene transcription RNAP subunit β, gene transcription RNAP subunit β’, gene transcription RNAP subunit ω, gene transcription sigma factor 70, major sigma factor sigma factor 32, regulation of heat shock proteins response regulator, important for biofilm formation in F. novicida, intracellular replication, interacting with MglA/SspA response regulator, regulation of potassium positive regulator of antimicrobial peptide resistance, regulation of biofilm in F. novicida [27,28,29,30,34,35]
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