The intracellular K level in bacteria is strictly controlled by K uptake and efflux systems. Among these, KdpFABC is a high-affinity K transporter system that is generally activated by the KdpDE two-component system in response to K limitation stress. However, the regulatory mechanism remains obscure in bacteria lacking the genes. Here we report that the transcription of a operon is distinctively regulated by a cyclic diadenylate monophosphate (c-di-AMP) riboswitch located at the 5'-untranslated region of transcript, and binding of c-di-AMP to the riboswitch promotes its intrinsic termination that blocks the transcription. Further, the intracellular c-di-AMP concentration was found to decrease under the K limitation stress, leading to transcriptional read-through over the terminator to allow expression. This regulatory element is found predominantly in the group and correlate well with the K and c-di-AMP homeostasis that affects a variety of crucial cellular functions.
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http://dx.doi.org/10.1038/s42003-019-0414-6 | DOI Listing |
Proc Natl Acad Sci U S A
December 2024
Department of Biochemistry, Brandeis University, Waltham, MA 02453.
The bacterial pathogen forms multicellular communities known as biofilms in which cells are held together by an extracellular matrix principally composed of repurposed cytoplasmic proteins and extracellular DNA. These biofilms assemble during infections or under laboratory conditions by growth on medium containing glucose, but the intracellular signal for biofilm formation and its downstream targets were unknown. Here, we present evidence that biofilm formation is triggered by a drop in the levels of the second messenger cyclic-di-AMP.
View Article and Find Full Text PDFmSphere
October 2024
Section of Molecular Microbiology and Centre for Bacterial Resistance Biology, Imperial College London, London, United Kingdom.
Nucleotide secondary messengers regulate various processes in bacteria allowing them to rapidly respond to changes in environmental conditions. c-di-AMP is an essential second messenger required for the growth of the human pathogen , regulating potassium, osmolyte uptake, and beta-lactam resistance. Cellular concentrations of c-di-AMP are regulated by the activities of two enzymes, DacA and GdpP, which synthesize and hydrolyze c-di-AMP, respectively.
View Article and Find Full Text PDFMicrobiol Spectr
August 2024
Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
The Gram-positive bacterium is the causative agent of anthrax and a bioterrorism threat worldwide. As a crucial second messenger in many bacterial species, cyclic di-AMP (c-di-AMP) modulates various key processes for bacterial homeostasis and pathogenesis. Overaccumulation of c-di-AMP alters cellular growth and reduces anthrax toxin expression as well as virulence in by unresolved underlying mechanisms.
View Article and Find Full Text PDFMicrolife
October 2023
Department of General Microbiology, GZMB, Georg-August-University Göttingen, Grisebachstr. 8, 37077 Göttingen, Germany.
The dinucleotide cyclic di-AMP (c-di-AMP) is synthesized as a second messenger in the Gram-positive model bacterium as well as in many bacteria and archaea. possesses three diadenylate cyclases and two phosphodiesterases that synthesize and degrade the molecule, respectively. Among the second messengers, c-di-AMP is unique since it is essential for on the one hand but toxic upon accumulation on the other.
View Article and Find Full Text PDFMicroorganisms
January 2023
Institute of Microbiology and Biotechnology, Ulm University, 89081 Ulm, Germany.
Cyclic di-adenosine monophosphate (c-di-AMP) is a bacterial second messenger discovered in and involved in potassium homeostasis, cell wall maintenance and/or DNA stress response. As the role of c-di-AMP has been mostly studied in Firmicutes, we sought to increase the understanding of its role in Actinobacteria, namely in . This organism is a well-known industrial production host and a model organism for pathogens, such as or .
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