Bacterial Indole as a Multifunctional Regulator of Klebsiella oxytoca Complex Enterotoxicity
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F22%3A73612950" target="_blank" >RIV/61989592:15310/22:73612950 - isvavai.cz</a>
Result on the web
<a href="https://journals.asm.org/doi/pdf/10.1128/mbio.03752-21" target="_blank" >https://journals.asm.org/doi/pdf/10.1128/mbio.03752-21</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1128/mbio.03752-21" target="_blank" >10.1128/mbio.03752-21</a>
Alternative languages
Result language
angličtina
Original language name
Bacterial Indole as a Multifunctional Regulator of Klebsiella oxytoca Complex Enterotoxicity
Original language description
Gastrointestinal microbes respond to biochemical metabolites that coordinate their behaviors. Here, we demonstrate that bacterial indole functions as a multifactorial mitigator of Klebsiella grimontii and Klebsiella oxytoca pathogenicity. These closely related microbes produce the enterotoxins tilimycin and tilivalline; cytotoxin-producing strains are the causative agent of antibiotic-associated hemorrhagic colitis and have been associated with necrotizing enterocolitis of premature infants. We demonstrate that carbohydrates induce cytotoxin synthesis while concurrently repressing indole biosynthesis. Conversely, indole represses cytotoxin production. In both cases, the alterations stemmed from differential transcription of npsA and npsB, key genes involved in tilimycin biosynthesis. Indole also enhances conversion of tilimycin to tilivalline, an indole analog with reduced cytotoxicity. In this context, we established that tilivalline, but not tilimycin, is a strong agonist of pregnane X receptor (PXR), a master regulator of xenobiotic detoxification and intestinal inflammation. Tilivalline binding upregulated PXR-responsive detoxifying genes and inhibited tubulin-directed toxicity. Bacterial indole, therefore, acts in a multifunctional manner to mitigate cytotoxicity by Klebsiella spp.: suppression of toxin production, enhanced conversion of tilimycin to tilivalline, and activation of PXR.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10606 - Microbiology
Result continuities
Project
<a href="/en/project/GA20-00449S" target="_blank" >GA20-00449S: Microbial catabolites of tryptophan as modulators of intestinal health via aryl hydrocarbon receptor</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
mBio
ISSN
2161-2129
e-ISSN
2150-7511
Volume of the periodical
13
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
19
Pages from-to
"e03752-21-1"-"e03752-21-19"
UT code for WoS article
000766822800003
EID of the result in the Scopus database
2-s2.0-85125860383