24AA Preclinical — In Vitro
Cloacaenodin
A novel antimicrobial lasso peptide from Enterobacter hormaechei with narrow-spectrum activity against carbapenem-resistant ESKAPE pathogens; preclinical only.
In Plain English: A naturally occurring 'knotted' peptide produced by gut-dwelling Enterobacter bacteria as a weapon against rival bacteria. Its slip-knotted lasso topology makes it resistant to digestion by enzymes that would destroy a conventional peptide. In laboratory studies it kills carbapenem-resistant Enterobacter strains — a group of hospital superbugs that can survive last-resort antibiotics — by infiltrating the bacterial cell through a specific 'gatekeeping' protein and then jamming the bacterial RNA-producing machinery.
Research Maturity
Preclinical — In Vitro (Studied in 2 primary research papers (2022–2024); Princeton patent application filed+ Studies)
Quick Facts
Focus
Antimicrobial
Gut Health
Infection Control
Route
In Vitro
Origin
Biosynthesized by Enterobacter hormaechei strain LB3 (isolated from long beans), Enterobacter cloacae strain B2 (bitter gourd), and Enterobacter kobei strain 15727 (human sputum, China). Discovered via precursor-centric genome mining and heterologous expression by the A. James Link lab at Princeton University (2022).
Mechanism
Two-step active import followed by RNA polymerase (RNAP) inhibition. Step 1 — outer membrane: cloacaenodin is captured by CloU, a strain-specific TonB-dependent transporter (TBDT) distinct from FhuA/PupB used by related lasso peptides. Step 2 — inner membrane: SbmA translocates the peptide into the cytoplasm. Once inside, conserved Tyr residues (analogous to microcin J25) are hypothesized to block the RNAP secondary channel, halting NTP entry and preventing trigger-loop folding. Sub-MIC concentrations induce bacterial filamentation, consistent with RNAP inhibition. Selective spectrum is primarily governed by CloU distribution — strains lacking CloU are intrinsically resistant.
Outcome
Selective bactericidal/bacteriostatic activity against Enterobacter cloacae complex members, including carbapenem-resistant clinical isolates (CRE). No activity against E. coli MG1655, Salmonella enterica, Klebsiella aerogenes, or Bacillus subtilis under standard conditions.
Safety Flags & Warnings
Preclinical Only — No Human Data
Patent Pending
Not Commercially Available
Narrow Spectrum — Off-Target Microbiome Risk
Always consult a licensed physician. Research purposes only.
€ / mg
