Scavenging of reactive oxygen species by tryptophan metabolites helps Pseudomonas aeruginosa escape neutrophil killing

Genestet, Charlotte; Gouellec, Audrey Le; Chaker, Hichem; Polack, Benoı̂t; Guery, Benoît; Toussaint, Bertrand; Stasia, Marie José

doi:10.1016/j.freeradbiomed.2014.06.003

Cited by 57 publications

(50 citation statements)

References 56 publications

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“…The metabolic profiles of wild type FVBN ovaries and FVB.129P2 Abcb1a tm1Bor Abcb1b tm1Bor Abcg2 tm1Ahs N7 ( mdr1a/mdr1b/bcrp−/−) in estrus showed statistically significant over-accumulation of orotate (CV=0.033 R=.982), dihydroorotate (CV=.001R=0.998) kynurenine (CV=.029 R=.979), and 3-ureidopropionate (CV=.035 R=.993). The premise that the knockout animals may be more susceptible to ROS is further supported by overexpression of kyreunine, which has been shown to scavenge hydrogen peroxide and superoxide [48]. The metabolite 3-ureidopropionate has been linked to neurotoxicity and generation of reactive oxygen species [49].…”

Section: 0 Resultsmentioning

confidence: 99%

Multidrug resistance transporter-1 and breast cancer resistance protein protect against ovarian toxicity, and are essential in ovarian physiology

Brayboy

Oulhen

Long

et al. 2017

Reproductive Toxicology

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Ovarian protection from chemotoxicity is essential for reproductive health. Our objective is to determine the role of ATP-dependent, Multidrug Resistance Transporters (MDRs) in this protection. Previously we identified MDR-dependent cytoprotection from cyclophosphamide in mouse and human oocytes by use of MDR inhibitors. Here we use genetic deletions in MDR1a/b/BCRP of mice to test MDR function in ovarian somatic cells and find that mdr1a/b/bcrp−/− mice had significantly increased sensitivity to cyclophosphamide. Further, estrus cyclicity and follicle distribution in mdr1a/b/bcrp−/− mice also differed from age-matched wildtype ovaries. We found that MDR gene activity cycles through estrus and that MDR-1b cyclicity correlated with 17β-estradiol surges. We also examined the metabolite composition of the ovary and learned that the mdr1a/b/bcrp−/− mice have increased accumulation of metabolites indicative of oxidative stress and inflammation. We conclude that MDRs are essential to ovarian protection from chemotoxicity and may have an important physiological role in the ovary.

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Section: 0 Resultsmentioning

confidence: 99%

Multidrug resistance transporter-1 and breast cancer resistance protein protect against ovarian toxicity, and are essential in ovarian physiology

Brayboy

Oulhen

Long

et al. 2017

Reproductive Toxicology

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“…Pseudomonas genera, can catabolize tryptophan into kynurenine via tryptophan 2,3-dioxygenase, kynA and kynurenine formamidase, kynB [133] ( Figure 1D). Whether intestinal proinflammatory cytokines or any other metabolites have similar effect on induction of kynA and kynB expression in this bacterium, and subsequent increased levels of downstream metabolites, is still unknown.…”

Section: The Dual Effect Of Gut Microbiota and Its Metabolites In Depmentioning

confidence: 99%

Role of Microbiota and Tryptophan Metabolites in the Remote Effect of Intestinal Inflammation on Brain and Depression

Waclawiková¹,

Aidy²

2018

Preprint

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The human gastrointestinal tract is inhabited by trillions of commensal bacteria collectively known as the gut microbiota. Our recognition of the significance of the complex interaction between the microbiota, and its host has grown dramatically over the past years. A balanced microbial community is a key regulator of the immune response, and metabolism of dietary components, which in turn, modulates several brain processes impacting mood and behavior. Consequently, it is likely that disruptions within the composition of the microbiota would remotely affect the mental state of the host. Here, we discuss how intestinal bacteria and their metabolites can orchestrate gut-associated neuroimmune mechanisms that influence mood and behavior leading to depression. In particular, we focus on microbiota-triggered gut inflammation and its implications in shifting the tryptophan metabolism towards kynurenine biosynthesis while disrupting the serotonergic signaling. We further investigate the gaps to be bridged in this exciting field of research in order to clarify our understanding of the multifaceted crosstalk in the microbiota-gut-brain interphase, bringing about a novel microbiota-targeted therapeutics for mental illnesses.

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“…However, P. aeruginosa is a very versatile pathogen and has developed multiple pathways to deal with potentially toxic exogenous compounds. For instance, it has been shown that P. aeruginosa neutralizes reactive oxygen species by tryptophan metabolites [36], expression of catalases [37], superoxide dismutase [38], etc. In this context, it is interesting to note that all three P. aeruginosa strains are sensitive to sphingosine.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils Kill Reactive Oxygen Species-Resistant Pseudomonas aeruginosa by Sphingosine

Becker

Seitz

et al. 2017

Cell Physiol Biochem

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Background/Aims: Cystic fibrosis (CF) is dominated by chronic inflammation and infection of the lung resulting in lung destruction and early death of patients. The lungs of CF patients are characterized by a massive accumulation of neutrophils. It requires definition why these massive numbers of neutrophils fail to eliminate typical CF pathogens like Staphylococcus aureus and Pseudomonas aeruginosa (P. aeruginosa) in CF lungs. Methods: We determined ceramide, sphingosine and reactive oxygen species (ROS) in neutrophils from wildtype and CF mice and determined the effect of sphingosine and ROS alone or in combination on killing of different P. aeruginosa strains. Results: We demonstrate that wildtype neutrophils are able to kill non-mucoid and mucoid clinical P. aeruginosa strains, while neutrophils from CF mice are insufficient to kill these P. aeruginosa strains, although both types of neutrophils infected with P. aeruginosa produce comparable levels of superoxide. All three analyzed P. aeruginosa strains are resistant to reactive oxygen species. The inability of CF neutrophils to kill P. aeruginosa is caused by a marked decrease of surface sphingosine levels in CF neutrophils. Wildtype neutrophils contain much higher concentrations of surface sphingosine than CF neutrophils. Further, wildtype neutrophils, but not CF neutrophils, release sphingosine, most likely as microparticles, upon infection. Sphingosine kills P. aeruginosa in vitro at low micromolar concentrations. Reconstitution of sphingosine in CF neutrophils restores their ability to kill these pathogens, demonstrating the significance of sphingosine for bacterial killing. Conclusion: The data provide evidence for a new paradigm explaining how neutrophils kill ROS-resistant P. aeruginosa, i.e. by sphingosine that kills P. aeruginosa at low concentrations. This mechanism is defective in CF neutrophils.

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Scavenging of reactive oxygen species by tryptophan metabolites helps Pseudomonas aeruginosa escape neutrophil killing

Cited by 57 publications

References 56 publications

Multidrug resistance transporter-1 and breast cancer resistance protein protect against ovarian toxicity, and are essential in ovarian physiology

Multidrug resistance transporter-1 and breast cancer resistance protein protect against ovarian toxicity, and are essential in ovarian physiology

Role of Microbiota and Tryptophan Metabolites in the Remote Effect of Intestinal Inflammation on Brain and Depression

Neutrophils Kill Reactive Oxygen Species-Resistant Pseudomonas aeruginosa by Sphingosine

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