Control of Francisella tularensis Virulence at Gene Level: Network of Transcription Factors

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.

Functional characterization of Francisella tularensis subspecies holarctica genotypes during tick cell and macrophage infections using a proteogenomic approach

“…PigR, a Francisella virulence factor (FevR) ortholog, is crucial for the expression of FPI genes within the MglA/SspA regulon ( Brotcke and Monack, 2008 ; Charity et al., 2009 ). The expression of FevR is upregulated by MglA, and the combined effect of FevR and MglA further enhances the upregulation of the expression of virulence genes ( Spidlova et al., 2020 ). The expression of PigR is also upregulated in the comparison between ticks and macrophages (LFC = 2.14).…”

“…Francisella modulates virulence through complex regulatory processes involving molecular signaling, gene transcription, translation and post-translational modifications. Pathogenicity is based on generating virulence factors that target host cells and suppress the immune response ( Spidlova et al., 2020 ). The major virulence factors of Ft include the capsule ( Su et al., 2007 ), the lipopolysaccharide layer on the surface ( Ancuta et al., 1996 ; Miller et al., 2005 ; Wang et al., 2007 ), membrane vesicles ( Golovliov et al., 2003 ; Klimentova et al., 2019 ), and secretion systems, in particular the type VI secretion system (T6SS) ( Lindgren et al., 2004 ; Nano et al., 2004 ; De Bruin et al., 2007 ; Bröms et al., 2010 ).…”

Tularaemia – a diagnostic challenge

“…Potential novel therapeutic strategies for tularaemia include the application of new antibiotics or developing new techniques for using existing ones, reduction of F. tularensis virulence, and enhancement of the innate and adaptive immune response of the host [100,101,102,103]. A new insight into the therapeutic approach in tularaemia is provided by the development of a new dye uptake assay to test the activity of antibiotics against intracellular F. tularensis [104].…”

Arginine 58 is indispensable for proper function of the Francisella tularensis subsp. holarctica FSC200 HU protein, and its substitution alters virulence and mediates immunity against wild-type strain

“…The regulation of FPI genes has been well described [ 6–10 ], but the regulation of other virulence genes is more or less unknown. To date, not many transcription regulators have been identified and described in Francisella [ 11 , 12 ]. Here, we contribute to a more detailed understanding of the HU protein functioning in F. tularensis subsp.…”

“…PigR is one of the transcription factors in Francisella spp. affecting virulence of the bacterium [ 12 ]. PigR, also termed FevR protein, is a necessary component of the PigR/MglA/SspA complex that regulates virulence gene expression in Francisella spp.…”