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Study · In vitro (cells) · pseudomonas aeruginosa and escherichia coli · 2014

5 results

Cationic antimicrobial peptides promote microbial mutagenesis and pathoadaptation in chronic infections.

Limoli DH, Rockel AB, Host KM, Jha A, Kopp BT, Hollis T, Wozniak DJ

PLoS pathogens24 Apr 2014Cited by 65 (Europe PMC)

PMID24763694 (opens in a new tab)PMCIDPMC3999168 (opens in a new tab)DOI10.1371/journal.ppat.1004083 (opens in a new tab)PepBankPUB-24763694
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Summary

Acquisition of adaptive mutations is essential for microbial persistence during chronic infections. This is particularly evident during chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients. Thus far, mutagenesis has been attributed to the generation of reactive species by polymorphonucleocytes (PMN) and antibiotic treatment. However, our current studies of mutagenesis leading to P. aeruginosa mucoid conversion have revealed a potential new mutagen. Our findings confirmed the current view that reactive oxygen species can promote mucoidy in vitro, but revealed PMNs are proficient at inducing mucoid conversion in the absence of an oxidative burst. This led to the discovery that cationic antimicrobial peptides can be mutagenic and promote mucoidy. Of specific interest was the human cathelicidin LL-37, canonically known to disrupt bacterial membranes leading to cell death. An alternative role was revealed at sub-inhibitory concentrations, where LL-37 was found to induce mutations within the mucA gene encoding a negative regulator of mucoidy and to promote rifampin resistance in both P. aeruginosa and Escherichia coli. The mechanism of mutagenesis was found to be dependent upon sub-inhibitory concentrations of LL-37 entering the bacterial cytosol and binding to DNA. LL-37/DNA interactions then promote translesion DNA synthesis by the polymerase DinB, whose error-prone replication potentiates the mutations. A model of LL-37 bound to DNA was generated, which reveals amino termini α-helices of dimerized LL-37 bind the major groove of DNA, with numerous DNA contacts made by LL-37 basic residues. This demonstrates a mutagenic role for antimicrobials previously thought to be insusceptible to resistance by mutation, highlighting a need to further investigate their role in evolution and pathoadaptation in chronic infections.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

4 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Mechanism

    At sub-inhibitory concentrations, LL‑37 induced mutations within the mucA gene, which encodes a negative regulator of mucoidy, in P. aeruginosa.

    In plain wordsIn lab tests, low levels of LL‑37 caused mutations in a bacterial gene that controls a slimy growth form.

    Peptide
    LL-37
    Outcome
    IncreaseMutations in mucA gene of P. aeruginosa
    Study

    Pseudomonas aeruginosan: not reported in source

    bacterial culture
    Outcome group
    Infection and antimicrobial activity · Infection
    Studied dose
    sub-inhibitory concentrationsAs given in this study (Pseudomonas aeruginosa).

    Source sentences

    Summary
    An alternative role was revealed at sub-inhibitory concentrations, where LL-37 was found to induce mutations within the mucA gene encoding a negative regulator of mucoidy
  2. 02LabIn vitro (cells)Safety outcome

    At sub-inhibitory concentrations, LL‑37 promoted rifampin resistance in both P. aeruginosa and Escherichia coli.

    In plain wordsIn lab tests, low levels of LL‑37 made two bacterial species more resistant to the antibiotic rifampin.

    Peptide
    LL-37
    Outcome
    IncreaseRifampin resistance in P. aeruginosa and E. coli
    Study

    Pseudomonas aeruginosa; Escherichia colin: not reported in source

    bacterial culture
    Outcome group
    Infection and antimicrobial activity · Infection
    Studied dose
    sub-inhibitory concentrationsAs given in this study (Pseudomonas aeruginosa; Escherichia coli).

    Source sentences

    Summary
    An alternative role was revealed at sub-inhibitory concentrations, where LL-37 was found to induce mutations within the mucA gene encoding a negative regulator of mucoidy and to promote rifampin resistance in both P. aeruginosa and Escherichia coli.
  3. 03LabIn vitro (cells)Mechanism

    Mutagenesis by LL‑37 depended on sub-inhibitory concentrations of LL‑37 entering the bacterial cytosol and binding to DNA.

    In plain wordsIn lab tests, LL‑37 caused mutations only when it entered the bacterial cell and bound to DNA.

    Peptide
    LL-37
    Outcome
    Not applicableMechanism of LL-37 mutagenesis: cytosolic entry and DNA binding
    Study

    Pseudomonas aeruginosa; Escherichia colin: not reported in source

    bacterial culture
    Outcome group
    Infection and antimicrobial activity · Infection
    Studied dose
    sub-inhibitory concentrationsAs given in this study (Pseudomonas aeruginosa; Escherichia coli).

    Source sentences

    Summary
    The mechanism of mutagenesis was found to be dependent upon sub-inhibitory concentrations of LL-37 entering the bacterial cytosol and binding to DNA.
  4. 04LabIn vitro (cells)Mechanism

    LL‑37/DNA interactions promoted translesion DNA synthesis by the polymerase DinB, whose error-prone replication potentiates the mutations.

    In plain wordsIn lab tests, LL‑37 bound to DNA led an error-prone copying enzyme to add mutations.

    Peptide
    LL-37
    Outcome
    Not applicableRole of polymerase DinB in LL-37 mutagenesis
    Study

    Pseudomonas aeruginosa; Escherichia colin: not reported in source

    bacterial culture
    Outcome group
    Infection and antimicrobial activity · Infection
    Studied dose
    sub-inhibitory concentrationsAs given in this study (Pseudomonas aeruginosa; Escherichia coli).

    Source sentences

    Summary
    LL-37/DNA interactions then promote translesion DNA synthesis by the polymerase DinB, whose error-prone replication potentiates the mutations.

Studies that did not test the peptide alone1

In this study, LL-37 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking LL-37.

  1. 05Computer modelNot a test of LL-37 aloneIn silicoMechanism

    A model of LL‑37 bound to DNA showed that amino-terminal alpha-helices of dimerized LL‑37 bind the major groove of DNA.

    In plain wordsA computer model predicts that LL‑37 binds the major groove of DNA through the start of its helices.

    Peptide
    LL-37
    Outcome
    Not applicablePredicted LL-37 and DNA binding
    Study

    n: not reported in source

    model of LL-37 bound to DNA
    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    A model of LL-37 bound to DNA was generated, which reveals amino termini α-helices of dimerized LL-37 bind the major groove of DNA, with numerous DNA contacts made by LL-37 basic residues.

    In this study, LL-37 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LL-37.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 3Current

    9 Oct 2026, 18:17 UTC

    Study results updated

  2. Version 2

    9 Oct 2026, 03:03 UTC

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 02:57 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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