Stress Suppressor Screening Leads to Detection of Regulation of Cyclic di-AMP Homeostasis by a Trk Family Effector Protein in Streptococcus pneumoniae

Journal of Bacteriology
Tiffany M ZarrellaGuangchun Bai

Abstract

Cyclic di-AMP (c-di-AMP) is a newly discovered bacterial second messenger. However, regulation of c-di-AMP homeostasis is poorly understood. In Streptococcus pneumoniae, a sole diadenylate cyclase, CdaA, produces c-di-AMP and two phosphodiesterases, Pde1 and Pde2, cleave the signaling dinucleotide. To expand our knowledge of the pneumococcal c-di-AMP signaling network, we performed whole-genome sequencing of Δpde1 Δpde2 heat shock suppressors. In addition to their effects on surviving heat shock, these suppressor mutations restored general stress resistance and improved growth in rich medium. Mutations in CdaA or in the potassium transporter TrkH paired with an insertion leading to a frameshift at the C terminus of CdaA significantly reduced c-di-AMP levels. These observations indicate that the elevated c-di-AMP levels in the Δpde1 Δpde2 mutant enhance susceptibility of S. pneumoniae to the stress conditions. Interestingly, we have previously shown that TrkH complexes with a Trk family c-di-AMP-binding protein, CabP, to mediate potassium uptake. In this study, we found that deletion of cabP significantly reduced pneumococcal c-di-AMP levels. This is the first observation that a c-di-AMP effector protein modulates bacterial c-di...Continue Reading

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Citations

Mar 13, 2019·Journal of Bacteriology·Huong Thi Pham, Mark S Turner
Nov 28, 2019·International Journal of Molecular Sciences·Rawana N AlkhaliliBjörn Canbäck
Nov 27, 2019·Journal of Bacteriology·Tiffany M ZarrellaGuangchun Bai
Apr 7, 2020·Environmental Microbiology·Johannes GibhardtFabian M Commichau
May 31, 2020·FEMS Microbiology Reviews·Wen YinJin He
Jul 1, 2020·Annual Review of Microbiology·Jörg Stülke, Larissa Krüger
Sep 30, 2020·FEMS Microbiology Reviews·Michiel KleerebezemOscar van Mastrigt
Jun 11, 2019·Annual Review of Microbiology·Erhard Bremer, Reinhard Krämer
Oct 7, 2020·Journal of Bacteriology·Steven M MassaTuAnh N Huynh
Aug 26, 2020·Journal of Bacteriology·Tiffany M Zarrella, Guangchun Bai
Mar 1, 2021·Current Opinion in Microbiology·Soo Hun Yoon, Christopher M Waters
Apr 2, 2021·Proceedings of the National Academy of Sciences of the United States of America·Tatiana B CereijaJoão H Morais-Cabral
Apr 14, 2021·Infection and Immunity·Clay D Jackson-LittekenJon S Blevins
Apr 21, 2021·Infection and Immunity·Elyza A Do, Casey M Gries

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