Metabolomics

Dataset Information

0

Dysregulation of Streptococcus pneumoniae zinc homeostasis breaks ampicillin resistance in a pneumonia infection model


ABSTRACT:

Streptococcus pneumoniae is the primary cause of community-acquired bacterial pneumonia with rates of penicillin and multi-drug resistance exceeding 80% and 40%, respectively. The innate immune response generates a variety of antimicrobial agents to control infection including zinc stress. Here, we characterized the impact of zinc intoxication on S. pneumoniae, revealing disruptions in central carbon metabolism, lipid biogenesis and peptidoglycan biosynthesis. Characterization of the pivotal peptidoglycan biosynthetic enzyme GlmU revealed an exquisite sensitivity to zinc inhibition. Disruption of the sole zinc efflux pathway, czcD, rendered S. pneumoniae highly susceptible to β-lactam antibiotics. To dysregulate zinc homeostasis in the wild-type strain, we investigated the safe-for-human use ionophore PBT2. PBT2 rendered wild-type S. pneumoniae strains sensitive to a range of antibiotics. Using an invasive ampicillin-resistant strain, we demonstrate in a murine pneumonia infection model the efficacy of PBT2+ampicillin treatment. These findings present a therapeutic modality to break resistance of drug-resistant S. pneumoniae.

INSTRUMENT(S): Q Exactive

SUBMITTER: Jason Rosch 

PROVIDER: MTBLS318 | MetaboLights | 2022-02-23

REPOSITORIES: MetaboLights

altmetric image

Publications


Streptococcus pneumoniae is the primary cause of community-acquired bacterial pneumonia with rates of penicillin and multidrug-resistance exceeding 80% and 40%, respectively. The innate immune response generates a variety of antimicrobial agents to control infection, including zinc stress. Here, we characterize the impact of zinc intoxication on S. pneumoniae, observing disruptions in central carbon metabolism, lipid biogenesis, and peptidoglycan biosynthesis. Characterization of the pivotal pep  ...[more]

Similar Datasets

2021-10-01 | GSE160372 | GEO
2021-02-25 | PXD022220 | Pride
2023-04-18 | GSE229867 | GEO
2022-02-01 | GSE159901 | GEO
2021-12-17 | GSE175535 | GEO
2023-10-24 | PXD037233 | Pride
2015-01-01 | GSE62045 | GEO
2022-10-12 | GSE201383 | GEO
2020-07-01 | GSE153553 | GEO
2024-10-01 | GSE272297 | GEO