Two-Component Systems in Francisella Species

Abstract

Bacteria alter gene expression in response to changes in their environment through various mechanisms that include signal transduction systems. These signal transduction systems use membrane histidine kinase with sensing domains to mediate phosphotransfer to DNA-binding proteins that alter the level of gene expression. Such regulators are called two-component systems (TCSs). TCSs integrate external signals and information from stress pathways, central metabolism and other global regulators, thus playing an important role as part of the overall regulatory network. This review will focus on the knowledge of TCSs in the Gram-negative bacterium, Francisella tularensis , a biothreat agent with a wide range of potential hosts and a significant ability to cause disease. While TCSs have been well-studied in several bacterial pathogens, they have not been well-studied in non-model organisms, such as F. tularensis and its subspecies, whose canonical TCS content surprisingly ranges from few to none. Additionally, of those TCS genes present, many are orphan components, including KdpDE, QseC, QseB/PmrA, and an unnamed two-component system (FTN_1452/FTN_1453). We discuss recent advances in this field related to the role of TCSs in Francisella physiology and pathogenesis and compare the TCS genes present in human virulent versus. environmental species and subspecies of Francisella .

Francisella novicida Two-Component System Response Regulator BfpR Modulates iglC Gene Expression, Antimicrobial Peptide Resistance, and Biofilm Production

“…Finally, in F. philomiragia, an environmental strain, and F. noatunensis, a fish pathogenic strain, three sensor kinase genes and three response regulator genes were identified, similar to F. novicida (van Hoek et al, 2019). We previously investigated the role of the response regulator QseB/PmrA (FTN_1465) in biofilm formation in F. novicida van Hoek, 2013), and demonstrated that biofilm formation is dependent on both the orphan response regulator (QseB/PrmA) and the orphan sensor kinase (QseC, FTN_1617). QseB/PmrA in F. novicida is critical for infection and has been identified as a potential virulence factor (Mohapatra et al, 2007;Bell et al, 2010).…”

“…F. novicida has been shown to form biofilms in vitro (Dean et al, 2009;Durham-Colleran et al, 2010;Margolis et al, 2010;Verhoeven et al, 2010;van Hoek, 2013). Biofilms play an important role in bacterial environmental survival and are often involved in pathogenicity and antimicrobial resistance.…”

“…In Pseudomonas, Salmonella, and many other Gram-negative bacteria, biofilm formation is under the control of twocomponent systems. Two-component systems are ubiquitous bacterial communication models and are typically formed from a membrane bound sensor histidine kinase and a DNAbinding response regulator (Stock et al, 2000;van Hoek et al, 2019). An extracellular signal is detected by the sensor kinase, resulting in autophosphorylation of the sensor kinase.…”

“…Only three response regulator (RR) genes have been identified in the Francisella genus. The two-component system gene organization varies across the different species (Figure 1; Larsson et al, 2005;van Hoek et al, 2019). F. novicida has three sensor kinase (SK) genes and three response regulator genes.…”

“…F. novicida has three sensor kinase (SK) genes and three response regulator genes. Two sets of genes form complete two-component system pairs (Figure 1), while the last two genes are "orphaned" (van Hoek et al, 2019). F. tularensis Schu S4, the highly infectious humanvirulent Type A strain, encodes two sensor kinase genes, two FIGURE 1 | Two component systems annotated or predicted in Francisella species.…”