Tiwari Sandeep, Jamal Syed B, Hassan Syed S, Carvalho Paulo V S D, Almeida Sintia, Barh Debmalya, Ghosh Preetam, Silva Artur, Castro Thiago L P, Azevedo Vasco
Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Biochemistry Group, Department of Chemistry, Islamia College University, Peshawar, Pakistan.
Front Microbiol. 2017 Oct 10;8:1878. doi: 10.3389/fmicb.2017.01878. eCollection 2017.
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.
广泛环境生态位中的细菌群落为了生存会感知并响应众多外部刺激。首先，它们进行这种通讯所需的一个来源是双组分信号转导系统（TCS），该系统通常包括一个用于接收外部输入信号的传感组氨酸激酶和一个能使细菌细胞生理发生适当变化的响应调节因子。由于多种原因，TCS已成为抗菌药物设计的有说服力的靶点。多项研究表明，TCS对于毒力因子的协调表达至关重要，在某些情况下，对细菌的生存能力和生长也至关重要。也有报道称，抗生素抗性决定因素的表达可能受某些TCS调控。此外，作为一种信号转导方式，细菌中组氨酸的磷酸化不同于高等真核生物中正常的丝氨酸/苏氨酸和酪氨酸磷酸化。多项研究揭示了TCS在病原菌中调控毒力和抗生素抗性的分子机制。在本综述中，我们列举了细菌TCS的一些特征及其在毒力和抗生素抗性中的作用。此外，本综述列出并讨论了已报道的针对病原菌中TCS的抑制剂。
