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Abstrato

Targeting Two-component Signal-transduction Systems of Bacteria for Good Potential Drug Design

Wei-Li Yu, Jiang-Ming Chen, Yun Sun and Xiao-Ping Geng

Background: The well-established scientific observation has shown that the process of sensing and making adaptive response to external stimuli in bacteria is regulated by the two-component signal-transduction systems (TCSTSs). Typical TCSTSs are composed of two different types of proteins, a histidine kinase (HK) and a response regulator (RR). This review focuses on the influence of TCSTSs on the virulence, competence, biofilm formation and antibiotic resistance, and further discusses the value of TCSTSs for the new drug targets.

Methods and findings: The HK protein is responsible for response to external stimuli by autophosphorylation, subsequently transfering this phosphate group to the RR protein, so then activating a series of biological processes. Loss of function or genetic mutation of these systems has been reported to study the function of the two component systems. It suggests that this system can regulate the expression of virulence factors, control the competence for transformation, modulate biofilm formation and cell envelope stress response, and influence the susceptibility to antibiotics.

Conclusion: The homologies of HK and RR proteins in different genera of bacteria are highly conserved respectively, especially in the residues located near active sites. Moreover the signal transduction in mammals has an entirely different mechanism compared with bacteria. Altogether, this system may be very suited as a good potential drug target for the development of novel antibacterial.