biostudies-literatureSandin DSpanish Ministerio de Ciencia e InnovaciónMinisterio de Ciencia e InnovaciónLa Caixa Banking FoundationEuropean Society of Clinical Microbiology and Infectious DiseasesEuropean Union Next GenerationEU/ PRTR to M.T.;Spanish Ministry of Economy and Innovation2169https://www.ebi.ac.uk/biostudies/studies/S-EPMC9611985biostudies-literatureUnknown14(10)Antimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can generate tolerance as an intermediate stage towards resistance is not known. Here, we show that the treatment of <i>Escherichia coli</i> with different AMPs induces tolerance by lag, particularly for those peptides that have internal targets. This tolerance can be detected as different morphological and physiological changes, which depend on the type of peptide molecule the bacterium has been exposed to. In addition, we show that AMP tolerance can also affect antibiotic treatment. The genomic sequePharmaceuticsAntimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial Therapy.PMC9611985ESCMID2022PID2020-114627RB-I00; PDC2021-121544-I00HR17-00409PID2020-114627RB-I00PDC2021-121544-I00Torrent MValle JSandin DMorata JAndreu DfalseAntimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial Therapy.Antimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can generate tolerance as an intermediate stage towards resistance is not known. Here, we show that the treatment of <i>Escherichia coli</i> with different AMPs induces tolerance by lag, particularly for those peptides that have internal targets. This tolerance can be detected as different morphological and physiological changes, which depend on the type of peptide molecule the bacterium has been exposed to. In addition, we show that AMP tolerance can also affect antibiotic treatment. The genomic seque2022-01-01T00:00:00Z2022 Oct2026-04-08T18:20:37.434Z2025-04-19T04:23:33.84ZS-EPMC96119853629760410.3390/pharmaceutics14102169