2007, 46, 3, 237-247



Marek Juda, Ewa Dadas, Anna Malm

Katedra i Zakład Mikrobiologii Farmaceutycznej Akademii Medycznej
im. Prof. F. Skubiszewskiego, ul. dr. W. Chodźki l, 20-093 Lublin,

Wpłynęło w lipcu 2006 r.

1. Wstęp. 2. Budowa dwuskładnikowych systemów regulacyjnych u bakterii. 3. Dwuskładnikowe systemy regulacyjne u bakterii Gram-dodatnich. 3.1. System AgrC/AgrA u Staphylococcus sp. 3.2. System BacR/BacS u Bacillus sp. 3.3. System VanS/VanR u Enterococcus faecalis. 3.4. System Kin/SpoOA u Bacillus subtilis 4. Dwuskładnikowe systemy regulacyjne u bakterii Gram-ujemnych. 4.1. Systemy AlgB/KinB i AlgR/AlgZ u Pseudomonas aeruginosa. 4.2. System BvgS/BvgA u Bordetella pertussis. 4.3. System EnvZ/OmpR u Escherichia coli 5. Dwuskładnikowe systemy regulacyjne u bakterii jako nowe potencjalne miejsca działania leków przeciwdrobnoustrojowych. 5.1. Naturalne inhibitory dwuskładnikowych systemów regulacyjnych. 5.2. Syntetyczne inhibitory dwuskładnikowych systemów regulacyjnych. 6. Podsumowanie

Significance of two-component regulatory systems in pathogenicity and drug resistance of bacteria

Abstract: Two-component regulatory systems are central elements of bacterial cell metabolism which recognize and respond to a variety of environmental stimuli like temperature, pH, osmolarity, Fe3+ concentration. This is accompanied by expression of genes including those encoding virulence factors and antibiotic resistance. These systems are composed of two basie elements - a histidine kinase and a response regulator. Histidine kinase, the integral membrane protein which recognizes environmental signals, catalyzes an ATP-dependent autophosphorylation of histidine residue (His). Subsequently the phosphoryl group is transferred to asparagine residue (Asp) of the cognate response regulator being a cytoplasmic protein. This is followed by activation or repression of genes being under the control of a given two-component regulatory system. Moreover, some of these systems are composed of additional proteins sequentially phosphorylated (His —» Asp —» His —» Asp) between histidine kinase and response regulator. The integral role of two-component regulatory systems in bacterial cells suggests that these systems may be no vel, promising targets for antibacterial agents. Two steps - the autophosphorylation of histidine kinase and the interaction between histidine kinase and response regulator can be considered as targets for action of chemical compounds. The conserved domains of the response regulator may represent the best target for inhibition. In recent years, various chemical compounds showing potential ability to inhibit two-component regulatory systems have been described.

1. Introduction. 2. Structure of two-component regulatory systems in bacteria. 3. Two-component regulatory systems in Gram-positive bacteria. 3.1. AgrC/AgrA system in Staphylococcus sp. 3.2. BacR/BacS system in Bacillus sp. 3.3. VanS/VanR system in Enterococcus faecalis. 3.4. Kin/SpoOA system in Bacillus subtilis 4. Two-component regulatory systems in Gram-negative bacteria. 4.1. AglB/KinB and AlgR/AlgZ systems in Pseudomonas aeruginosa. 4.2. BvgS/BvgA system in Bordetella pertussis. 4.3. EnvZ/OmpR system in Escherichia coli. 5. Two-component regulatory systems as new, potential targets for antimicrobial agents. 5.1. Natural inhibitors of two-component regulatory systems. 5.2. Synthetic inhibitors of two-component regulatory systems. 6. Summary

Słowa kluczowe: dwuskładnikowy system regulacyjny, kinaza histydynowa,
                         regulator odpowiedzi, regulacja ekspresji genów
Key words: two-component regulatory systems, histidine kinase, response
                   regulator, regulation of gene expression


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