Abstract

Cutaneous bacterial infections frequently elicit severe pruritus, prominently featuring alloknesis, a pathological state where innocuous touch provokes intense itch. However, the peripheral mechanisms translating microbial cues into touch-evoked pruritus remain unresolved. Here, we establish an epicutaneous Pseudomonas aeruginosa infection model that robustly isolates mechanical alloknesis from spontaneous scratching. We identify bacterial flagellin as the critical virulence factor driving this specific sensory modality via Toll-like receptor 5 (TLR5) activation exclusively within Calb1+ A{beta} rapidly adapting low-threshold mechanoreceptors (RA-LTMRs). Mechanistically, pathogen-driven TLR5 signaling depletes intracellular PIP2, which suppresses KCNQ4-mediated M-currents and dismantles the biophysical brake on LTMR excitability. Our findings define a distinct microbial-neuronal axis that directly converts tactile stimuli into itch at the peripheral entry point, providing an infection-based framework for dissecting pathogen-sensory neuron interactions and uncovering precise therapeutic targets for chronic, touch-evoked pruritus.