Murepavadin induces envelope stress response and enhances the killing efficacies of β-lactam antibiotics by impairing the outer membrane integrity of Pseudomonas aeruginosa.

Wei X, Gao J, Xu C, Pan X, Jin Y, Bai F, Cheng Z, Lamont IL, Pletzer D, Wu W

Microbiology spectrum5 Sept 2023Cited by 16 (Europe PMC)

PMID37668398PMCIDPMC10581190DOI10.1128/spectrum.01257-23PepBankPUB-37668398

Summary

ImportanceThe ever increasing resistance of bacteria to antibiotics poses a serious threat to global public health. Novel antibiotics and treatment strategies are urgently needed. Murepavadin is a novel antibiotic that blocks the assembly of lipopolysaccharide (LPS) into the Pseudomonas aeruginosa outer membrane by inhibiting LPS transport protein D (LptD). Here, we demonstrated that murepavadin impairs bacterial outer membrane integrity, which induces the envelope stress response. We further found that the impaired outer membrane integrity increases the influx of β-lactam antibiotics, resulting in enhanced bactericidal effects. In addition, the combination of murepavadin and a β-lactam/β-lactamase inhibitor mixture (ceftazidime/avibactam) slowed down the resistance development of P. aeruginosa. Overall, this study demonstrates the bacterial response to murepavadin and provides a new combination strategy for effective treatment.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

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

01LabIn vitro (cells)Mechanism
In bacteria, murepavadin impaired outer membrane integrity.
In plain wordsIn lab tests, murepavadin impaired bacterial outer membrane integrity.
Peptide
Murepavadin
Outcome
DecreaseOuter membrane integrity
Study
Pseudomonas aeruginosan: not reported in source
Pseudomonas aeruginosa cultures
Outcome group
Receptor activity and mechanism · Infection
Studied dose
Dose not stated
Source sentences
Summary
Here, we demonstrated that murepavadin impairs bacterial outer membrane integrity, which induces the envelope stress response.
Show in the study text Report a problemFND-3766839801
02LabIn vitro (cells)Mechanism
In bacteria, murepavadin-induced membrane impairment induced the envelope stress response.
In plain wordsIn lab tests, murepavadin induced the bacterial envelope stress response.
Peptide
Murepavadin
Outcome
IncreaseEnvelope stress response
Study
Pseudomonas aeruginosan: not reported in source
Pseudomonas aeruginosa cultures
Outcome group
Receptor activity and mechanism · Infection
Studied dose
Dose not stated
Source sentences
Summary
Here, we demonstrated that murepavadin impairs bacterial outer membrane integrity, which induces the envelope stress response.
Show in the study text Report a problemFND-3766839802

Studies that did not test the peptide alone3

In this study, Murepavadin 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 Murepavadin.

03LabNot a test of Murepavadin aloneIn vitro (cells)Mechanism
In bacteria, membrane impairment associated with murepavadin increased beta-lactam antibiotic influx.
In plain wordsIn lab tests, membrane impairment associated with murepavadin increased antibiotic entry into bacteria.
Peptide
Murepavadin
Outcome
IncreaseBeta-lactam influx
Study
Pseudomonas aeruginosan: not reported in source
Pseudomonas aeruginosa cultures
Outcome group
Receptor activity and mechanism · Infection
Source sentences
Summary
We further found that the impaired outer membrane integrity increases the influx of β-lactam antibiotics, resulting in enhanced bactericidal effects.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we demonstrated that murepavadin impairs bacterial outer membrane integrity, which induces the envelope stress response.
In this study, Murepavadin 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 Murepavadin.
Show in the study text Report a problemFND-3766839803
04LabNot a test of Murepavadin aloneIn vitro (cells)Activity measurement
In bacteria, murepavadin-associated membrane impairment enhanced beta-lactam bactericidal effects.
In plain wordsIn lab tests, murepavadin-associated membrane impairment enhanced antibiotic bacterial killing.
Peptide
Murepavadin
Outcome
IncreaseBeta-lactam bactericidal efficacy
Study
Pseudomonas aeruginosan: not reported in source
Pseudomonas aeruginosa cultures
Outcome group
Infection and antimicrobial activity · Infection
Source sentences
Summary
We further found that the impaired outer membrane integrity increases the influx of β-lactam antibiotics, resulting in enhanced bactericidal effects.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we demonstrated that murepavadin impairs bacterial outer membrane integrity, which induces the envelope stress response.
In this study, Murepavadin 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 Murepavadin.
Show in the study text Report a problemFND-3766839804
05LabNot a test of Murepavadin aloneIn vitro (cells)Activity measurement
In Pseudomonas aeruginosa, murepavadin with ceftazidime/avibactam slowed resistance development.
In plain wordsIn lab tests, murepavadin with ceftazidime/avibactam slowed bacterial resistance development.
Peptide
Murepavadin
Outcome
DecreaseResistance development
Study
Pseudomonas aeruginosan: not reported in source
Pseudomonas aeruginosa cultures
Outcome group
Infection and antimicrobial activity · Infection
Source sentences
Summary
In addition, the combination of murepavadin and a β-lactam/β-lactamase inhibitor mixture (ceftazidime/avibactam) slowed down the resistance development of P. aeruginosa.
In this study, Murepavadin 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 Murepavadin.
Show in the study text Report a problemFND-3766839805

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.

Version 2Current
27 Oct 2026, 18:20 UTC
Study results updated
Version 1
27 Oct 2026, 16:32 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

Keywords

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