biostudies-literatureLedala NAustrian Science Fund FWFConnecticut Children&apos;s Department of ResearchOffice of Assistant Secretary of Defense for Health AffairsCzech Science FoundationConnecticut Children&apos;s Stevenson Fund for Microbiome Researche0375221https://www.ebi.ac.uk/biostudies/studies/S-EPMC8787480biostudies-literatureUnknown13(1)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 <i>npsA</i> and <i>npsB</i>, key genes involved in tilimycin biosymBioBacterial Indole as a Multifunctional Regulator of Klebsiella oxytoca Complex Enterotoxicity.PMC8787480DOC 5020-00449SW901W81XWH-17-1-0479Kortagere SLedala NProvatas AZhou YMani SMalik MRezaul KRadolf JDGhosh SCosic AKiel AKrasulova KIlles PDvorak ZPoltl LPaveglio SCaimano MLindgren JZechner ELKienesberger SMatson APfalseBacterial Indole as a Multifunctional Regulator of Klebsiella oxytoca Complex Enterotoxicity.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 <i>npsA</i> and <i>npsB</i>, key genes involved in tilimycin biosy2022-01-01T00:00:00Z2022 Feb2026-06-07T03:18:48.597Z2025-04-19T10:48:31.292ZS-EPMC87874803507374710.1128/mbio.03752-21