Abstract
The abundance of two-component systems (TCSs) in Streptomyces coelicolor A3(2) genome indicates their importance in the physiology of this soil bacteria. Currently, several TCSs have been related to antibiotic regulation, and the purpose in this study was the characterization of five TCSs, selected by sequence homology with the well-known absA1A2 system, that could also be associated with this important process. Null mutants of the five TCSs were obtained and two mutants (ΔSCO1744/1745 and ΔSCO4596/4597/4598) showed significant differences in both antibiotic production and morphological differentiation, and have been renamed as abr (antibiotic regulator). No detectable changes in antibiotic production were found in the mutants in the systems that include the ORFs SCO3638/3639, SCO3640/3641 and SCO2165/2166 in any of the culture conditions assayed. The system SCO1744/1745 (AbrA1/A2) was involved in negative regulation of antibiotic production, and acted also as a negative regulator of the morphological differentiation. By contrast, the system SCO4596/4597/4598 (AbrC1/C2/C3), composed of two histidine kinases and one response regulator, had positive effects on both morphological development and antibiotic production. Microarray analyses of the ΔabrC1/C2/C3 and wild-type transcriptomes revealed downregulation of actII-ORF4 and cdaR genes, the actinorhodin and calcium-dependent antibiotic pathway-specific regulators respectively. These results demonstrated the involvement of these new two-component systems in antibiotic production and morphological differentiation by different approaches. One is a pleiotropic negative regulator: abrA1/A2. The other one is a positive regulator composed of three elements, two histidine kinases and one response regulator: abrC1/C2/C3.
Highlights
Antibiotics are highly valuable secondary metabolites that are broadly produced in different species of the genus Streptomyces, a filamentous soil bacterium with a complex life cycle
Both differentiation and antibiotic production can be triggered by many environmental changes, such as nutrient deprivation, pH, temperature, etc
To determine the relevance of these five twocomponent systems (TCSs) in antibiotic production, null mutant strains of each system were obtained from the S. coelicolor M145 strain by the REDIRECT procedure
Summary
Antibiotics are highly valuable secondary metabolites that are broadly produced in different species of the genus Streptomyces, a filamentous soil bacterium with a complex life cycle. The onset of antibiotic production depends on the growth stage of the microorganism and usually takes place contemporaneous with differentiation of the aerial mycelium into spores. Both differentiation and antibiotic production can be triggered by many environmental changes (physical and chemical), such as nutrient deprivation, pH, temperature, etc. The quickest and most efficient bacterial responses to extracellular stimuli occur via histidineaspartate (His-Asp) phosphorelay cascades These systems are made up of inner membrane-spanning protein kinases, which sense the external environment, and their respective (cognate) cytoplasmic response regulator partners, which generally exhibit DNA-binding properties. Some atypical systems have been described, such as a kinase phosphorylated by GTP instead of ATP [3] and the phosphorylation independent activation response regulators, named PIARR [4,5,6]
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