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MetaboLights MTBLS1191 - GNPS Absence of tmRNA increases the persistence to cefotaxime by upregulating the metabolites GlcNAc in Aeromonas veronii

ABSTRACT:

Bacterial persisters refer to a small proportion of phenotypically heterogeneous variants with transient capability for survival when exposing to high concentrations of antibiotic, which constitute the major cause for recurrent infections both in human and aquatic infections. In pathogenic bacteria Aeromonas veronii, tmRNA (transfer-messenger RNA), the core factor of trans-translation system, was identified as a determinant regulator mediating the persistence to ?-lactams. Compared with the wild type, the deletion of tmRNA exhibited unchanged growth rate, sustained susceptibility to cefotaxime, but did increase persister cell formation. Transcriptomic and metabolomic analyses revealed that, the absence of tmRNA not only upreglated the expressions of metabolic genes especially in the metabolic flux of peptidoglycan biosynthesis, but also significantly elevated the intercellular level of metabolite GlcNAc, thereby intensifying the contents of peptidoglycans in the cell wall. Eventually, exogenous GlcNAc stimulated significantly the bacterial growth and persistence to cefotaxime in a concentration dependent manner. Taken together, these results uncover a novel mechanism of persister formation mediated by tmRNA against the ?-lactam challenges.

INSTRUMENT(S): TripleTOF 5600+|1002584

ORGANISM(S): Aeromonas Veronii|654

SUBMITTER: Yu Wenjing

PROVIDER: MSV000085752 | GNPS | Tue Jul 14 15:55:00 BST 2020

REPOSITORIES: GNPS

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Absence of tmRNA increases the persistence to cefotaxime by upregulating the metabolites GlcNAc in Aeromonas veronii

Project description:Bacterial persisters refer to a small proportion of phenotypically heterogeneous variants with transient capability for survival when exposing to high concentrations of antibiotic, which constitute the major cause for recurrent infections both in human and aquatic infections. In pathogenic bacteria Aeromonas veronii, tmRNA (transfer-messenger RNA), the core factor of trans-translation system, was identified as a determinant regulator mediating the persistence to β-lactams. Compared with the wild type, the deletion of tmRNA exhibited unchanged growth rate, sustained susceptibility to cefotaxime, but did increase persister cell formation. Transcriptomic and metabolomic analyses revealed that, the absence of tmRNA not only upreglated the expressions of metabolic genes especially in the metabolic flux of peptidoglycan biosynthesis, but also significantly elevated the intercellular level of metabolite GlcNAc, thereby intensifying the contents of peptidoglycans in the cell wall. Eventually, exogenous GlcNAc stimulated significantly the bacterial growth and persistence to cefotaxime in a concentration dependent manner. Taken together, these results uncover a novel mechanism of persister formation mediated by tmRNA against the β-lactam challenges.

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Project 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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