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

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

doi:10.1073/pnas.1909604116

Cited by 41 publications

(62 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Q is highly conserved and found in plants, fishes, insects, and mammals. While many bacteria can synthesize queuine (the nucleobase of Q) de novo, salvaging the prokaryotic Q precursors preQ 0 and preQ 1 has recently been reported [ 62 ]. Eukaryotes are not capable of Q synthesis and they rely on salvaging the queuine base as a Q precursor either by nutrition or by the intestinal bacterial flora [ 63 , 64 , 65 ].…”

Section: Response Of E Histolytica To Os In Prmentioning

confidence: 99%

Entamoeba histolytica—Gut Microbiota Interaction: More Than Meets the Eye

Ankri

2021

Microorganisms

View full text Add to dashboard Cite

Amebiasis is a disease caused by the unicellular parasite Entamoeba histolytica. In most cases, the infection is asymptomatic but when symptomatic, the infection can cause dysentery and invasive extraintestinal complications. In the gut, E. histolytica feeds on bacteria. Increasing evidences support the role of the gut microbiota in the development of the disease. In this review we will discuss the consequences of E. histolytica infection on the gut microbiota. We will also discuss new evidences about the role of gut microbiota in regulating the resistance of the parasite to oxidative stress and its virulence.

show abstract

Section: Response Of E Histolytica To Os In Prmentioning

confidence: 99%

Entamoeba histolytica—Gut Microbiota Interaction: More Than Meets the Eye

Ankri

2021

Microorganisms

View full text Add to dashboard Cite

show abstract

“…Eubacteria can synthesize the queuine nucleobase precursor of queuosine de novo . However, a recent study showed that some Eubacteria can also salvage precursors of queuosine ( 11 ). Since mammals cannot synthesize queuine and salvage it from diet and gut microbes, these observations suggest a dynamic supply and demand for queuine by both the gut microbiota and the host ( 12 – 14 ).…”

Section: Introductionmentioning

confidence: 99%

Queuine Is a Nutritional Regulator of Entamoeba histolytica Response to Oxidative Stress and a Virulence Attenuator

Nagaraja

Cai

Sun

et al. 2021

mBio

Self Cite

View full text Add to dashboard Cite

Queuosine is a naturally occurring modified ribonucleoside found in the first position of the anticodon of the transfer RNAs for Asp, Asn, His, and Tyr. Eukaryotes lack pathways to synthesize queuine, the nucleobase precursor to queuosine, and must obtain it from diet or gut microbiota. Here, we describe the effects of queuine on the physiology of the eukaryotic parasite Entamoeba histolytica, the causative agent of amebic dysentery. Queuine is efficiently incorporated into E. histolytica tRNAs by a tRNA-guanine transglycosylase (EhTGT) and this incorporation stimulates the methylation of C38 in tRNAGUCAsp. Queuine protects the parasite against oxidative stress (OS) and antagonizes the negative effect that oxidation has on translation by inducing the expression of genes involved in the OS response, such as heat shock protein 70 (Hsp70), antioxidant enzymes, and enzymes involved in DNA repair. On the other hand, queuine impairs E. histolytica virulence by downregulating the expression of genes previously associated with virulence, including cysteine proteases, cytoskeletal proteins, and small GTPases. Silencing of EhTGT prevents incorporation of queuine into tRNAs and strongly impairs methylation of C38 in tRNAGUCAsp, parasite growth, resistance to OS, and cytopathic activity. Overall, our data reveal that queuine plays a dual role in promoting OS resistance and reducing parasite virulence. IMPORTANCE Entamoeba histolytica is a unicellular parasite that causes amebiasis. The parasite resides in the colon and feeds on the colonic microbiota. The gut flora is implicated in the onset of symptomatic amebiasis due to alterations in the composition of bacteria. These bacteria modulate the physiology of the parasite and affect the virulence of the parasite through unknown mechanisms. Queuine, a modified nucleobase of queuosine, is exclusively produced by the gut bacteria and leads to tRNA modification at the anticodon loops of specific tRNAs. We found that queuine induces mild oxidative stress resistance in the parasite and attenuates its virulence. Our study highlights the importance of bacterially derived products in shaping the physiology of the parasite. The fact that queuine inhibits the virulence of E. histolytica may lead to new strategies for preventing and/or treating amebiasis by providing to the host queuine directly or via probiotics.

show abstract

“…In other words, the availability of a nutrient varies throughout the process of gut colonization. It is therefore not surprising that many microorganisms have both a salvage and a biosynthetic pathway for a given nutrient, in order to survive in fluctuating and sometimes crowded gut environments [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Interplay between Yersinia pestis and its flea vector in lipoate metabolism

et al. 2021

View full text Add to dashboard Cite

To thrive, vector-borne pathogens must survive in the vector’s gut. How these pathogens successfully exploit this environment in time and space has not been extensively characterized. Using Yersinia pestis (the plague bacillus) and its flea vector, we developed a bioluminescence-based approach and employed it to investigate the mechanisms of pathogenesis at an unprecedented level of detail. Remarkably, lipoylation of metabolic enzymes, via the biosynthesis and salvage of lipoate, increases the Y. pestis transmission rate by fleas. Interestingly, the salvage pathway’s lipoate/octanoate ligase LplA enhances the first step in lipoate biosynthesis during foregut colonization but not during midgut colonization. Lastly, Y. pestis primarily uses lipoate provided by digestive proteolysis (presumably as lipoyl peptides) rather than free lipoate in blood, which is quickly depleted by the vector. Thus, spatial and temporal factors dictate the bacterium’s lipoylation strategies during an infection, and replenishment of lipoate by digestive proteolysis in the vector might constitute an Achilles’ heel that is exploited by pathogens.

show abstract

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

Cited by 41 publications

References 75 publications

Entamoeba histolytica—Gut Microbiota Interaction: More Than Meets the Eye

Entamoeba histolytica—Gut Microbiota Interaction: More Than Meets the Eye

Queuine Is a Nutritional Regulator of Entamoeba histolytica Response to Oxidative Stress and a Virulence Attenuator

Interplay between Yersinia pestis and its flea vector in lipoate metabolism

Contact Info

Product

Resources

About