ppGpp is a ubiquitous small
nucleotide messenger that mediates cellular self-protective responses under environmental stress. However, the mechanisms of
ppGpp that control transcription and other metabolic processes depend on the species, and
ppGpp regulates the same process via different mechanisms. The level of
ppGpp is regulated by RelA/SpoT homolog (RSH)
enzymes that synthesize and hydrolyze the
alarmone. Here, we constructed a ppGpp0 strain and monitored the effects of
ppGpp on the transcriptional level, physiology, and secondary metabiotic production in the
antibiotic producer Streptomyces diastatochromogenes 1628. The results showed the cell division and growth of ppGpp0 increased by measurement of gene transcription and DCWs. The utilization of
nitrogen was affected depending on the
nitrogen type with a significantly higher DCW of the ppGpp0 mutant in the medium supplied with the yeast extract and a lower growth rate in the inorganic
nitrogen ammonium salt. The
ppGpp-mediated stringent response could not affect the usage of
carbon resources. More importantly, ppGpp0 inhibited the expression of
antibiotic clusters and the production of
toyocamycin and
tetramycin P. The antibiotic resistance was also significantly downregulated in the ppGpp0 mutant. In conclusion, this study showed detailed changes in
ppGpp-mediated stringent responses on S. diastatochromogenes 1628 cell growth, nutrient utilization, morphological characteristics,
antibiotic production, and resistance, which will provide insights into the role of
ppGpp in Streptomyces. IMPORTANCE The
ppGpp-mediated stringent response is widely distributed in Escherichia coli, Bacillus subtilis, Streptomyces, Staphylococcus aureus, etc. Stringent responses give strains the ability to resist environmental stresses, and survival from nutrition
starvation, virulence, long-term persistence, biofilm formation, and gut colonization.
ppGpp has many targets in cells and can reprogram DNA replication, transcription, ribosome biogenesis and function, and lipid metabolism. However, the mechanism of
ppGpp to control transcription and other metabolic processes depends on the bacterial species and regulates the same process via a different mechanism. In Streptomyces, how
ppGpp regulates the transcription remains to be elucidated. However, because
ppGpp regulates many genes involved in primary and secondary metabolism, we compared the transcription and cell division, cell growth, morphological differentiation, antibiotic resistance, and secondary synthesis in the wild-type S. diastatochromogenes and ppGpp0 strains.