Screening of the Pandemic Response Box library identified promising compound candidate drug combinations against extensively drug-resistant Acinetobacter baumannii.

Boonyalai N, Peerapongpaisarn D, Thamnurak C, Oransathid W, Wongpatcharamongkol N, Oransathid W, Lurchachaiwong W, Griesenbeck JS, Waters NC, Demons ST, Ruamsap N, Vesely BA

Scientific reports17 Sept 2024Cited by 1 (Europe PMC)

PMID39289446PMCIDPMC11408719DOI10.1038/s41598-024-72603-9PepBankPUB-39289446

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Summary

Infections caused by antimicrobial-resistant Acinetobacter baumannii pose a significant threat to human health, particularly in the context of hospital-acquired infections. As existing antibiotics lose efficacy against Acinetobacter isolates, there is an urgent need for the development of novel antimicrobial agents. In this study, we assessed 400 structurally diverse compounds from the Medicines for Malaria Pandemic Response Box for their activity against two clinical isolates of A. baumannii: A. baumannii 5075, known for its extensive drug resistance, and A. baumannii QS17-1084, obtained from an infected wound in a Thai patient. Among the compounds tested, seven from the Pathogen box exhibited inhibitory effects on the in vitro growth of A. baumannii isolates, with IC₅₀s ≤ 48 µM for A. baumannii QS17-1084 and IC₅₀s ≤ 17 µM for A. baumannii 5075. Notably, two of these compounds, MUT056399 and MMV1580854, shared chemical scaffolds resembling triclosan. Further investigations involving drug combinations identified five synergistic drug combinations, suggesting potential avenues for therapeutic development. The combination of MUT056399 and brilacidin against A. baumannii QS17-1084 and that of MUT056399 and eravacycline against A. baumannii 5075 showed bactericidal activity. These combinations significantly inhibited biofilm formation produced by both A. baumannii strains. Our findings highlight the drug combinations as promising candidates for further evaluation in murine wound infection models against multidrug-resistant A. baumannii. These compounds hold potential for addressing the critical need for effective antibiotics in the face of rising antimicrobial resistance.

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

Results from this study2

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone2

In this study, Brilacidin 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 Brilacidin.

01LabNot a test of Brilacidin aloneIn vitro (cells)Activity measurement
In A. baumannii QS17-1084 laboratory tests, MUT056399 plus brilacidin showed bactericidal activity.
In plain wordsIn lab tests, MUT056399 plus brilacidin killed Acinetobacter baumannii QS17-1084.
Peptide
Brilacidin
Outcome
Not applicableCombination bactericidal activity
Study
Acinetobacter baumanniin: not reported in source
Acinetobacter baumannii QS17-1084
Outcome group
Infection and antimicrobial activity · Infection
Source sentences
Summary
The combination of MUT056399 and brilacidin against A. baumannii QS17-1084 and that of MUT056399 and eravacycline against A. baumannii 5075 showed bactericidal activity.
In this study, Brilacidin 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 Brilacidin.
Show in the study text Report a problemFND-3928944601
02LabNot a test of Brilacidin aloneIn vitro (cells)Activity measurement
In laboratory tests, MUT056399 plus brilacidin significantly inhibited biofilm formation by A. baumannii QS17-1084.
In plain wordsIn lab tests, MUT056399 plus brilacidin reduced biofilm formation by Acinetobacter baumannii QS17-1084.
Peptide
Brilacidin
Outcome
DecreaseCombination biofilm inhibition
Study
Acinetobacter baumanniin: not reported in source
Acinetobacter baumannii QS17-1084
Outcome group
Infection and antimicrobial activity · Infection
Source sentences
Summary
These combinations significantly inhibited biofilm formation produced by both A. baumannii strains.
1 context sentence(design, population, supporting numbers)
Summary · context
The combination of MUT056399 and brilacidin against A. baumannii QS17-1084 and that of MUT056399 and eravacycline against A. baumannii 5075 showed bactericidal activity.
In this study, Brilacidin 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 Brilacidin.
Show in the study text Report a problemFND-3928944602

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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

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