Absence of tmRNA Increases the Persistence to Cefotaxime and the Intercellular Accumulation of Metabolite GlcNAc in Aeromonas veronii

Bacterial persisters are a small proportion of phenotypically heterogeneous variants with the transient capability to survive in high concentrations of antibiotics, causing recurrent infections in both human and aquatic animals. Transfer-messenger RNA (tmRNA), which was encoded by the ssrA gene, was...

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Main Authors: Wenjing Yu, Daiyu Li, Hong Li, Yanqiong Tang, Hongqian Tang, Xiang Ma, Zhu Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-02-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fcimb.2020.00044/full
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author Wenjing Yu
Wenjing Yu
Daiyu Li
Hong Li
Yanqiong Tang
Hongqian Tang
Xiang Ma
Zhu Liu
author_facet Wenjing Yu
Wenjing Yu
Daiyu Li
Hong Li
Yanqiong Tang
Hongqian Tang
Xiang Ma
Zhu Liu
author_sort Wenjing Yu
collection DOAJ
description Bacterial persisters are a small proportion of phenotypically heterogeneous variants with the transient capability to survive in high concentrations of antibiotics, causing recurrent infections in both human and aquatic animals. Transfer-messenger RNA (tmRNA), which was encoded by the ssrA gene, was identified as a determinant regulator mediating the persistence to β-lactams in the pathogenic Aeromonas veronii C4. The deletion of tmRNA exhibited the increased ability of persister formation most probably due to the reduction of protein synthesis. Transcriptomic and metabolomic analyses revealed that the absence of tmRNA not only significantly elevated the intercellular levels of metabolite GlcNAc and promoted NaCl osmotic tolerance, but also upregulated the expression of metabolic genes in both the upstream biosynthesis pathway and the downstream metabolic flux of peptidoglycan (PG) biosynthesis. Finally, exogenous GlcNAc stimulated significant bacterial growth, enhanced content of GlcNAc in the cell wall, higher resistance to osmotic response, and higher persistence to cefotaxime in a concentration-dependent manner, implying its potential role in promoting the multiple phenotypes observed in tmRNA deletion strains. Taken together, these results hint at a potential mechanism of persister formation mediated by tmRNA against the β-lactam challenges in A. veronii.
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spelling doaj.art-d1d8953b140b46139ff9b16a14e484042022-12-21T20:25:49ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-02-011010.3389/fcimb.2020.00044495777Absence of tmRNA Increases the Persistence to Cefotaxime and the Intercellular Accumulation of Metabolite GlcNAc in Aeromonas veroniiWenjing Yu0Wenjing Yu1Daiyu Li2Hong Li3Yanqiong Tang4Hongqian Tang5Xiang Ma6Zhu Liu7Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Pharmaceutical Sciences, Hainan University, Haikou, ChinaSchool of Tropical Crops, Hainan University, Haikou, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Pharmaceutical Sciences, Hainan University, Haikou, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Pharmaceutical Sciences, Hainan University, Haikou, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Pharmaceutical Sciences, Hainan University, Haikou, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Pharmaceutical Sciences, Hainan University, Haikou, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Pharmaceutical Sciences, Hainan University, Haikou, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Pharmaceutical Sciences, Hainan University, Haikou, ChinaBacterial persisters are a small proportion of phenotypically heterogeneous variants with the transient capability to survive in high concentrations of antibiotics, causing recurrent infections in both human and aquatic animals. Transfer-messenger RNA (tmRNA), which was encoded by the ssrA gene, was identified as a determinant regulator mediating the persistence to β-lactams in the pathogenic Aeromonas veronii C4. The deletion of tmRNA exhibited the increased ability of persister formation most probably due to the reduction of protein synthesis. Transcriptomic and metabolomic analyses revealed that the absence of tmRNA not only significantly elevated the intercellular levels of metabolite GlcNAc and promoted NaCl osmotic tolerance, but also upregulated the expression of metabolic genes in both the upstream biosynthesis pathway and the downstream metabolic flux of peptidoglycan (PG) biosynthesis. Finally, exogenous GlcNAc stimulated significant bacterial growth, enhanced content of GlcNAc in the cell wall, higher resistance to osmotic response, and higher persistence to cefotaxime in a concentration-dependent manner, implying its potential role in promoting the multiple phenotypes observed in tmRNA deletion strains. Taken together, these results hint at a potential mechanism of persister formation mediated by tmRNA against the β-lactam challenges in A. veronii.https://www.frontiersin.org/article/10.3389/fcimb.2020.00044/fullAeromonas veroniiβ-lactamspersistersGlcNAcpeptidoglycan biosynthesis
spellingShingle Wenjing Yu
Wenjing Yu
Daiyu Li
Hong Li
Yanqiong Tang
Hongqian Tang
Xiang Ma
Zhu Liu
Absence of tmRNA Increases the Persistence to Cefotaxime and the Intercellular Accumulation of Metabolite GlcNAc in Aeromonas veronii
Frontiers in Cellular and Infection Microbiology
Aeromonas veronii
β-lactams
persisters
GlcNAc
peptidoglycan biosynthesis
title Absence of tmRNA Increases the Persistence to Cefotaxime and the Intercellular Accumulation of Metabolite GlcNAc in Aeromonas veronii
title_full Absence of tmRNA Increases the Persistence to Cefotaxime and the Intercellular Accumulation of Metabolite GlcNAc in Aeromonas veronii
title_fullStr Absence of tmRNA Increases the Persistence to Cefotaxime and the Intercellular Accumulation of Metabolite GlcNAc in Aeromonas veronii
title_full_unstemmed Absence of tmRNA Increases the Persistence to Cefotaxime and the Intercellular Accumulation of Metabolite GlcNAc in Aeromonas veronii
title_short Absence of tmRNA Increases the Persistence to Cefotaxime and the Intercellular Accumulation of Metabolite GlcNAc in Aeromonas veronii
title_sort absence of tmrna increases the persistence to cefotaxime and the intercellular accumulation of metabolite glcnac in aeromonas veronii
topic Aeromonas veronii
β-lactams
persisters
GlcNAc
peptidoglycan biosynthesis
url https://www.frontiersin.org/article/10.3389/fcimb.2020.00044/full
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