Role Of Two-Component Signal Transduction Systems In Antimicrobial Resistance Of Gram-Negative Pathogens

Two-component signal transduction systems composed of histidine sensor kinase and response regulator are involved in adaptive response of pathogenic bacteria to environmental signals by regulating gene expression involved in many physiological processes, bacterial virulence, and antibiotic resistance (antibacterial compounds). Antibiotic resistance of pathogenic bacteria is one of the most important public health problems worldwide. The paper describes a signal transduction mechanism based on phosphotransfer, functioning in two-component systems and the mechanisms of antibiotic resistance governed by these systems. Several signal transduction pathways associated with resistance to antibacterial compounds and functioning in Pseudomonas aeruginosa, Acinetobacter baumannii, Aeromonas, Salmonella and Yersinia spp. have been characterized (PhoP-PhoQ, PmrA-PmrB, ParR-ParS, CzcR-CzcS, CopR-CopS, PprB-PprA, CbrB-CbrA, BlrA-BlrB and OmpR-EnvZ systems). Their role in modifying the bacterial cell surface, limiting the inflow or increasing the drug efflux from the cell, producing antibiotic-degrading enzymes or the biofilm formation is presented.

1. Introduction. 2. Mechanism of action of two-component regulatory systems. 2.1. Histidine sensor kinases. 2.2. Response regulators. 2.3. Signal transduction in two-component systems. 3. Mechanisms of antibiotic resistance controlled by two-component signal transduction systems. 3.1. Cell surface modification. 3.2. Regulation of drug inflow and outflow. 3.3. Regulation of the level of enzymes modifying/inactivating antibiotics. 3.4. Other alternative forms of resistance. 4. Characteristics of two-component signal transduction systems modulating resistance to antibacterial compounds in selected Gram-negative bacteria. 4.1. PhoP-PhoQ and PmrA-PmrB systems. 4.2. ParR-ParS system. 4.3. CzcR-CzcS and CopR-CopS systems. 4.4. PprB-PprA system. 4.5. CbrB-CbrA system. 4.6. BlrA-BlrB system. 4.7. OmpR-EnvZ system. 5. Summary