articlebioRxiv (Cold Spring Harbor Laboratory)Mar 19, 2026GREEN OA

The broad-spectrum RumC1 bacteriocin targets a transient peptidoglycan intermediate of the nascent cell wall

ABAnne BoyeldieuMBMathieu BergéCRClarisse RoblinLSLAMA SHAMSEDDINEAMAnna M. Díaz-Rovira

Lutheran Medical Group · Centrale Marseille · +12 more institutions

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Abstract

RumC1 is a structurally unique bacteriocin with broad-spectrum efficacy, including against multidrug-resistant pathogens, yet acting by an undefined mechanism. By integrating genetics, biochemistry, computational modeling and single-cell fluorescence microscopy, we demonstrate that RumC1 is a distinct cell-wall-targeting toxin. First, all RumC1-resistant mutants isolated through a high-rate, genome-wide mutagenic screening exhibited specific impairments in peptidoglycan homeostasis regulation, pinpointing this pathway as critical for RumC1 activity. Second, RumC1 selectively accumulates within neosynthesized peptidoglycan, leading to cell growth arrest and death in a dose-dependent manner. Third, we…

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Topics & keywords

Topics
Keywords
  • Peptidoglycan
  • Bacteriocin
  • Cell wall
  • Mutant
  • Cell
  • Peptide
  • Lysis
  • Cell envelope
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