Guanosine penta- or tetraphosphate (known as (p)ppGpp) serves as second messenger to respond to nutrient downshift and other environmental stresses, a phenomenon called stringent response. Accumulation of (p)ppGpp promotes the coordinated inhibition of macromolecule synthesis, as well as the activation of stress response pathways to cope and adapt to harmful conditions. In , the (p)ppGpp level is tightly regulated by two enzymes, the (p)ppGpp synthetase RelA and the bifunctional synthetase/hydrolase SpoT. We recently identified the small protein YtfK as a key regulator of SpoT-mediated activation of stringent response in . Here, we further characterized the regulation of . We observed that is subjected to catabolite repression and is positively regulated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex. Importantly, YtfK contributes to SpoT-dependent accumulation of (p)ppGpp and cell survival in response to glucose starvation. Therefore, regulation of by the cAMP-CRP appears important to adjust (p)ppGpp level and coordinate cellular metabolism in response to glucose availability.
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http://dx.doi.org/10.3389/fmicb.2021.775164 | DOI Listing |
mBio
November 2024
Lab of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
Gene expression and proper downstream cellular functions upon facing environmental shifts depend on the combined and cooperative regulation of genetic networks. Here, we identified cAMP receptor protein (CRP) as a master regulator of (p)ppGpp (guanosine tetra- and penta-phosphate) homeostasis. Via CRP-mediated direct transcriptional regulation of the (p)ppGpp synthetase/hydrolase RelA and SpoT, cAMP-CRP stimulates pervasive accumulation of (p)ppGpp under glucose-limiting conditions.
View Article and Find Full Text PDFFront Microbiol
July 2024
Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, China.
Introduction: Bacterial resistance presents a major challenge to both the ecological environment and human well-being, with persistence playing a key role. Multiple studies were recently undertaken to examine the factors influencing the formation of persisters and the underlying process, with a primary focus on Gram-negative bacteria and (Gram-positive bacteria). Enterococcus faecalis () is capable of causing a variety of infectious diseases, but there have been few studies of persisters.
View Article and Find Full Text PDFMicrobiology (Reading)
July 2024
Department of Chemistry and Biochemistry, Old Dominion University, Norfolk, Virginia, 23529, USA.
The bacterial stringent response (SR) is a conserved transcriptional reprogramming pathway mediated by the nucleotide signalling alarmones, (pp)pGpp. The SR has been implicated in antibiotic survival in , a biofilm- and spore-forming pathogen that causes resilient, highly recurrent infections. The role of the SR in other processes and the effectors by which it regulates physiology are unknown.
View Article and Find Full Text PDFWorld J Gastroenterol
June 2024
Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing 100034, China.
Background: (HP), the most common pathogenic microorganism in the stomach, can induce inflammatory reactions in the gastric mucosa, causing chronic gastritis and even gastric cancer. HP infection affects over 4.4 billion people globally, with a worldwide infection rate of up to 50%.
View Article and Find Full Text PDFVavilovskii Zhurnal Genet Selektsii
February 2024
Institute of Ecology and Genetics of Microorganisms of the Ural Branch of the Russian Academy of Sciences, Perm, Russia.
Bacterial stress adaptive response is formed due to changes in the cell gene expression profile in response to alterations in environmental conditions through the functioning of regulatory networks. The mutual influence of network signaling molecules represented by cells' natural metabolites, including indole and second messengers (p) ppGpp and cAMP, is hitherto not well understood, being the aim of this study. E.
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