Cellular Effects of 29,39-Cyclic Nucleotide Monophosphates in Gram-Negative Bacteria

Yashasvika Duggal, Jennifer E. Kurasz, Benjamin M. Fontaine, Nick J. Marotta, Shikha S. Chauhan, Anna C. Karls, Emily E. Weinert

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Organismal adaptations to environmental stimuli are governed by intracellular signaling molecules such as nucleotide second messengers. Recent studies have identified functional roles for the noncanonical 29,39-cyclic nucleotide monophosphates (29,39-cNMPs) in both eukaryotes and prokaryotes. In Escherichia coli, 29,39-cNMPs are produced by RNase I-catalyzed RNA degradation, and these cyclic nucleotides modulate biofilm formation through unknown mechanisms. The present work dissects cellular processes in E. coli and Salmonella enterica serovar Typhimurium that are modulated by 29,39-cNMPs through the development of cell-permeable 29,39-cNMP analogs and a 29,39-cyclic nucleotide phosphodiesterase. Utilization of these chemical and enzymatic tools, in conjunction with phenotypic and transcriptomic investigations, identified pathways regulated by 29,39-cNMPs, including flagellar motility and biofilm formation, and by oligoribonucleotides with 39-terminal 29,39-cyclic phosphates, including responses to cellular stress. Furthermore, interrogation of metabolomic and organismal databases has identified 29,39-cNMPs in numerous organisms and homologs of the E. coli metabolic proteins that are involved in key eukaryotic pathways. Thus, the present work provides key insights into the roles of these understudied facets of nucleotide metabolism and signaling in prokaryotic physiology and suggest broad roles for 29,39-cNMPs among bacteria and eukaryotes. IMPORTANCE Bacteria adapt to environmental challenges by producing intracellular signaling molecules that control downstream pathways and alter cellular processes for survival. Nucleotide second messengers serve to transduce extracellular signals and regulate a wide array of intracellular pathways. Recently, 29,39-cyclic nucleotide monophosphates (29,39-cNMPs) were identified as contributing to the regulation of cellular pathways in eukaryotes and prokaryotes. In this study, we define previously unknown cell processes that are affected by fluctuating 29,39-cNMP levels or RNA oligomers with 29,39-cyclic phosphate termini in E. coli and Salmonella Typhimurium, providing a framework for studying novel signaling networks in prokaryotes. Furthermore, we utilize metabolomics databases to identify additional prokaryotic and eukaryotic species that generate 29,39-cNMPs as a resource for future studies.

Original languageEnglish (US)
Article numbere00208-21
JournalJournal of bacteriology
Issue number1
StatePublished - Jan 2022

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology


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