Rationale and prospects of targeting bacterial 2-component systems

Antimicrobial resistance is a major societal problem as there are resistant bacteria to any antibiotic available, and they spread across countries and continents. For this a novel antibacterial medicine with a low potential of resistance development is urgently needed. Researchers from Spain, The Netherlands, and United Kingdom have joined efforts to identify bacterial histidine kinase inhibitors that can be further developed as novel antibacterial medicines.

Cystic fibrosis (CF) is a genetic disorder in which the patients develop chronic bacterial infections caused mainly by Pseudomonas aeruginosa in the lungs, but there are also other pathogens involved in the lung disease typical for CF patients. All these pathogens rely on histidine kinases, as part of two-component systems to adapt to the diseased lung. In a recent publication in Current Drug Targets the potential to use bacterial histidine kinase inhibitors to treat bacterial infections in CF patients is studied by reviewing key TCS of different pathogens involved in CF lung disease.

The reviewed TCS are involved in the regulation of, among others, virulence, biofilm formation, and antibiotics resistance in pathogens common for lung disease in CF patients such as S. aureus, H. influenza, P. aeruginosa, and B. cepacia. Taken together with the presence of TCS in all major pathogens in CF and the conservation of the TCS domains, TCS inhibitors alone or in combination with currently used antibacterial treatment present an option for treating bacterial infections in CF patients worth exploring.

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Reference: Velikova, N.; (2017). Rationale and Prospects of Targeting Bacterial Two-component Systems for Antibacterial Treatment of Cystic Fibrosis Patients. Current Drug Targets., DOI: 10.2174/1389450117666160208145934

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