Abstract
Cell death within bacterial communities can benefit surviving cells by releasing nutrients, genetic material, and extracellular polymers that reinforce biofilms and activate adaptive programs such as sporulation. Dying cells also influence the antibiotic tolerance of neighboring bacteria, often by inducing efflux pathways or sequestering antimicrobial compounds. Here, we describe a distinct tolerance mechanism in which extracellular RNA (eRNA) reduces susceptibility to the cationic antibiotics kanamycin, gentamicin, and polymyxin B by limiting their cellular uptake. This RNA-mediated sequestration depends on inherent features of cell death and RNA chemistry, with only structured RNA species conferring protection. Isothermal titration calorimetry reveals micromolar binding of kanamycin and gentamicin to tRNA, while polymyxin B binds more weakly. Because RNA is abundant, rapidly released during cell lysis, and strongly polyanionic, it can broadly modulate antibiotic activity across diverse bacteria and environments. These findings expand death-derived tolerance factors and highlight a population-level RNA-driven mechanism of resilience in microbes.
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This work was supported by National Institutes of Health Grant GM118085 to R.M.H.
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Kumar, V., Perez, M., Bhattacharyya, S. et al. Extracellular RNA confers tolerance to cationic antibiotics by sequestering them.
Commun Biol (2026). https://doi.org/10.1038/s42003-026-10859-9
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DOI: https://doi.org/10.1038/s42003-026-10859-9
Source: Ecology - nature.com
