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Pathogenic and Commensal Gut Bacteria Harboring Glycerol/Diol Dehydratase Metabolize Glycerol and Produce DNA-Reactive Acrolein

Ramirez Garcia, Alejandro and Hurley, Katherine and Marastoni, Giovanni and Diard, Médéric and Hofer, Sophie and Greppi, Anna and Hardt, Wolf-Dietrich and Lacroix, Christophe and Sturla, Shana J. and Schwab, Clarissa. (2022) Pathogenic and Commensal Gut Bacteria Harboring Glycerol/Diol Dehydratase Metabolize Glycerol and Produce DNA-Reactive Acrolein. Chemical research in toxicology, 35 (10). pp. 1840-1850.

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Official URL: https://edoc.unibas.ch/93738/

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Abstract

Bacteria harboring glycerol/diol dehydratase (GDH) encoded by the genes; pdu; CDE metabolize glycerol and release acrolein during growth. Acrolein has antimicrobial activity, and exposure of human cells to acrolein gives rise to toxic and mutagenic responses. These biological responses are related to acrolein's high reactivity as a chemical electrophile that can covalently bind to cellular nucleophiles including DNA and proteins. Various food microbes and gut commensals transform glycerol to acrolein, but there is no direct evidence available for bacterial glycerol metabolism giving rise to DNA adducts. Moreover, it is unknown whether pathogens, such as; Salmonella; Typhymurium, catalyze this transformation. We assessed, therefore, acrolein formation by four GDH-competent strains of; S.; Typhymurium grown under either aerobic or anaerobic conditions in the presence of 50 mM glycerol. On the basis of analytical derivatization with a heterocyclic amine, all wild-type strains were observed to produce acrolein, but to different extents, and acrolein production was not detected in fermentations of a; pdu; C-deficient mutant strain. Furthermore, we found that, in the presence of calf thymus DNA, acrolein-DNA adducts were formed as a result of bacterial glycerol metabolism by two strains of; Limosilactobacillus reuteri; , but not a; pdu; CDE mutant strain. The quantification of the resulting adducts with increasing levels of glycerol up to 600 mM led to the production of up to 1.5 mM acrolein and 3600 acrolein-DNA adducts per 10; 8; nucleosides in a model system. These results suggest that GDH-competent food microbes, gut commensals, and pathogens alike have the capacity to produce acrolein from glycerol. Further, the acrolein production can lead to DNA adduct formation, but requires high glycerol concentrations that are not available in the human gut.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Pathogen Evolution (Diard)
UniBasel Contributors:Diard, Médéric
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society (ACS)
ISSN:0893-228X
e-ISSN:1520-5010
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:27 Mar 2023 10:35
Deposited On:27 Mar 2023 10:35

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