A product of heme catabolism modulates bacterial function and survival.

Bilirubin is the terminal metabolite in heme catabolism in mammals. After deposition into bile, bilirubin is released in large quantities into the mammalian gastrointestinal (GI) tract. We hypothesized that intestinal bilirubin may modulate the function of enteric bacteria. To test this hypothesis,...

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Main Authors: Christopher L Nobles, Sabrina I Green, Anthony W Maresso
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC3723568?pdf=render
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author Christopher L Nobles
Sabrina I Green
Anthony W Maresso
author_facet Christopher L Nobles
Sabrina I Green
Anthony W Maresso
author_sort Christopher L Nobles
collection DOAJ
description Bilirubin is the terminal metabolite in heme catabolism in mammals. After deposition into bile, bilirubin is released in large quantities into the mammalian gastrointestinal (GI) tract. We hypothesized that intestinal bilirubin may modulate the function of enteric bacteria. To test this hypothesis, we investigated the effect of bilirubin on two enteric pathogens; enterohemorrhagic E. coli (EHEC), a Gram-negative that causes life-threatening intestinal infections, and E. faecalis, a Gram-positive human commensal bacterium known to be an opportunistic pathogen with broad-spectrum antibiotic resistance. We demonstrate that bilirubin can protect EHEC from exogenous and host-generated reactive oxygen species (ROS) through the absorption of free radicals. In contrast, E. faecalis was highly susceptible to bilirubin, which causes significant membrane disruption and uncoupling of respiratory metabolism in this bacterium. Interestingly, similar results were observed for other Gram-positive bacteria, including B. cereus and S. aureus. A model is proposed whereby bilirubin places distinct selective pressure on enteric bacteria, with Gram-negative bacteria being protected from ROS (positive outcome) and Gram-positive bacteria being susceptible to membrane disruption (negative outcome). This work suggests bilirubin has differential but biologically relevant effects on bacteria and justifies additional efforts to determine the role of this neglected waste catabolite in disease processes, including animal models.
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spelling doaj.art-08163f1851b147d8b155d784a97088762022-12-22T01:31:47ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-0197e100350710.1371/journal.ppat.1003507A product of heme catabolism modulates bacterial function and survival.Christopher L NoblesSabrina I GreenAnthony W MaressoBilirubin is the terminal metabolite in heme catabolism in mammals. After deposition into bile, bilirubin is released in large quantities into the mammalian gastrointestinal (GI) tract. We hypothesized that intestinal bilirubin may modulate the function of enteric bacteria. To test this hypothesis, we investigated the effect of bilirubin on two enteric pathogens; enterohemorrhagic E. coli (EHEC), a Gram-negative that causes life-threatening intestinal infections, and E. faecalis, a Gram-positive human commensal bacterium known to be an opportunistic pathogen with broad-spectrum antibiotic resistance. We demonstrate that bilirubin can protect EHEC from exogenous and host-generated reactive oxygen species (ROS) through the absorption of free radicals. In contrast, E. faecalis was highly susceptible to bilirubin, which causes significant membrane disruption and uncoupling of respiratory metabolism in this bacterium. Interestingly, similar results were observed for other Gram-positive bacteria, including B. cereus and S. aureus. A model is proposed whereby bilirubin places distinct selective pressure on enteric bacteria, with Gram-negative bacteria being protected from ROS (positive outcome) and Gram-positive bacteria being susceptible to membrane disruption (negative outcome). This work suggests bilirubin has differential but biologically relevant effects on bacteria and justifies additional efforts to determine the role of this neglected waste catabolite in disease processes, including animal models.http://europepmc.org/articles/PMC3723568?pdf=render
spellingShingle Christopher L Nobles
Sabrina I Green
Anthony W Maresso
A product of heme catabolism modulates bacterial function and survival.
PLoS Pathogens
title A product of heme catabolism modulates bacterial function and survival.
title_full A product of heme catabolism modulates bacterial function and survival.
title_fullStr A product of heme catabolism modulates bacterial function and survival.
title_full_unstemmed A product of heme catabolism modulates bacterial function and survival.
title_short A product of heme catabolism modulates bacterial function and survival.
title_sort product of heme catabolism modulates bacterial function and survival
url http://europepmc.org/articles/PMC3723568?pdf=render
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