Mechanistic Insights into Human Antimicrobial Peptide-Induced Activation of a Broadly Conserved Bacterial Signaling System.

ABSTRACT: Antimicrobial peptides (AMPs) represent a promising class of therapeutics against bacterial pathogens. While their direct bactericidal mechanisms are well-characterized, how bacteria sense and respond to these peptides at sublethal concentrations remains poorly understood. Here, we investigate the activation of the Escherichia coli PhoQ-PhoP signaling system by the human cathelicidin LL-37 and its derivatives (KR-12 and RI-10). We demonstrate that these peptides exhibit variable antimicrobial potency but surprisingly similar abilities to activate the PhoQ-PhoP pathway, indicating that signaling function is separable from bactericidal activity. Notably, sublethal concentrations of these peptides induce significant cell elongation, a phenotype dependent on PhoQ and mediated by the upr

SUBMITTER: Adeleye SA 

PROVIDER: S-EPMC12080957 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature