|
ROLA DWUSKŁADNIKOWYCH SYSTEMÓW
REGULACYJNYCH W CHOROBOTWÓRCZOŚCI
I LEKOOPORNOŚCI BAKTERII
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,
e-mail:
anna.malm@am.lublin.pl
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
|
