Journal Article

Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens

Payan, Daniel J., Swairjo, Manal A., Liu, Chuan-Fa, Dedon, Peter C., Gerlt, John A., Grove, Tyler L., Yuan, Yifeng, Almo, Steven C., Balamkundu, Seetharamsingh, Neelakandan, Ramesh, Šepić, Sara, Gadi, Vinod K., de Crécy-Lagard, Valérie, Zallot, Rémi, Martin-Verstraete, Isabelle

2019

Overview

Queuosine (Q) is a complex tRNA modification widespread in eukaryotes and bacteria that contributes to the efficiency and accuracy of protein synthesis. Eukaryotes are not capable of Q synthesis and rely on salvage of the queuine base (q) as a Q precursor. While many bacteria are capable of Q de novo synthesis, salvage of the prokaryotic Q precursors preQ₀ and preQ₁ also occurs. With the exception of Escherichia coli YhhQ, shown to transport preQ₀ and preQ₁, the enzymes and transporters involved in Q salvage and recycling have not been well described. We discovered and characterized 2 Q salvage pathways present in many pathogenic and commensal bacteria. The first, found in the intracellular pathogen Chlamydia trachomatis, uses YhhQ and tRNA guanine transglycosylase (TGT) homologs that have changed substrate specificities to directly salvage q, mimicking the eukaryotic pathway. The second, found in bacteria from the gut flora such as Clostridioides difficile, salvages preQ₁ from q through an unprecedented reaction catalyzed by a newly defined subgroup of the radical-SAM enzyme family. The source of q can be external through transport by members of the energy-coupling factor (ECF) family or internal through hydrolysis of Q by a dedicated nucleosidase. This work reinforces the concept that hosts and members of their associated microbiota compete for the salvage of Q precursors micronutrients.

• Publisher: National Academy of Sciences
• Subject: Bacteria / Bacterial Proteins - metabolism / BASIC BIOLOGICAL SCIENCES / Biochemistry, Molecular Biology / Biological Sciences / Chlamydia Infections - metabolism / Chlamydia Infections - microbiology / Chlamydia trachomatis - growth & development / Chlamydia trachomatis - metabolism / Clostridioides difficile - growth & development / Clostridioides difficile - metabolism / Clostridium Infections - metabolism / Clostridium Infections - microbiology / comparative genomics / E coli / Enzymes / Eukaryotes / Guanine / Guanine - analogs & derivatives / Guanine - metabolism / Homology / Humans / Intestinal microflora / Life Sciences / Microbiology / Microbiota / Micronutrients / Mimicry / nucleoside transport / Pathogens / Pentosyltransferases - metabolism / PNAS Plus / Precursors / Protein biosynthesis / Protein synthesis / Queues / Queuosine / RNA, Transfer - genetics / RNA, Transfer - metabolism / rSAM / sequence similarity network / Signal Transduction / Subgroups / Substrate Specificity / Substrates / Transport / tRNA / tRNA Ala