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Abstract
The bacterial communities in a wide range of environmental niches sense and respond to numerous external stimuli for their survival. Primarily, a source they require to follow up this communication is the two-component signal transduction system (TCS), which typically comprises a sensor Histidine kinase for receiving external input signals and a response regulator that conveys a proper change in the bacterial cell physiology. For numerous reasons, TCSs have ascended as convincing targets for antibacterial drug design. Several studies have shown that TCSs are essential for the coordinated expression of virulence factors and, in some cases, for bacterial viability and growth. It has also been reported that the expression of antibiotic resistance determinants may be regulated by some TCSs. In addition, as a mode of signal transduction, phosphorylation of histidine in bacteria differs from normal serine/threonine and tyrosine phosphorylation in higher eukaryotes. Several studies have shown the molecular mechanisms by which TCSs regulate virulence and antibiotic resistance in pathogenic bacteria. In this review, we list some of the characteristics of the bacterial TCSs and their involvement in virulence and antibiotic resistance. Furthermore, this review lists and discusses inhibitors that have been reported to target TCSs in pathogenic bacteria.
Highlights
Microbes are the most versatile living organisms on the planet
Bacterial transduction system (TCS) As Drug Targets conferred by a specialized signal transduction mechanism, which relies on the two-component systems (TCSs) (Cheung and Hendrickson, 2010; Groisman, 2016)
As each particular TCS is specialized to respond to a specific environmental signal, multiple TCSs may be present in a single bacterial cell
Summary
Microbes are the most versatile living organisms on the planet. They can be found in environments where plants and animals cannot survive, such as in hydrothermal vents on the ocean floor or glaciers. Since protein phosphorylation has been discovered to take place in bacterial nitrogen absorption and chemotaxis, a number of techniques have been developed to study Two-component signal transduction systems (Scharf, 2010) The use of these techniques has allowed identification of stimuliresponsive TCSs, such as PhoPQ TCSs. PhoPQ is known to respond to a wide variety of environmental stress signals, including phosphate (Ogura et al, 2001; Pragai and Harwood, 2002), Mg2+ and Ca2+ starvation, pH, antimicrobial peptides and nutritional deprivation (Hall, 1998; Regelmann et al, 2002; Fontan et al, 2004; Miyashiro and Goulian, 2008). Genomic sequencing of C. pseudotuberculosis has revealed 10 of these signal transduction systems (Figure 1) (Barakat et al, 2011)
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