Evidence map›Paper›PMID 39596774›Full record

ArticleAntibiotics (Basel, Switzerland)2024

Enhancing Antibacterial Efficacy: Combining Novel Bacterial Topoisomerase Inhibitors with Efflux Pump Inhibitors and Other Agents Against Gram-Negative Bacteria.

Maša Zorman, Maja Kokot, Irena Zdovc, Lidija Senerovic, Mina Mandic, Nace Zidar, Andrej Emanuel Cotman, Martina Durcik, Lucija Peterlin Mašič, Nikola Minovski and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antibiotics (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Maša ZormanTheory Department, Laboratory for Cheminformatics, National Institute of Chemistry, Hajdrihova 19, 1001 Ljubljana, Slovenia.ORCID 0009-0002-0939-2146
Maja KokotTheory Department, Laboratory for Cheminformatics, National Institute of Chemistry, Hajdrihova 19, 1001 Ljubljana, Slovenia.
Irena ZdovcInstitute of Microbiology and Parasitology, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, 1000 Ljubljana, Slovenia.ORCID 0000-0002-5419-2779
Lidija SenerovicLaboratory for Microbial Molecular Genetics and Ecology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11042 Belgrade, Serbia.
Mina MandicLaboratory for Microbial Molecular Genetics and Ecology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11042 Belgrade, Serbia.ORCID 0000-0002-3246-6230
Nace ZidarDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva Cesta 7, 1000 Ljubljana, Slovenia.ORCID 0000-0003-1905-0158
Andrej Emanuel CotmanDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva Cesta 7, 1000 Ljubljana, Slovenia.ORCID 0000-0003-2528-396X
Martina DurcikDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva Cesta 7, 1000 Ljubljana, Slovenia.ORCID 0000-0002-9218-1771
Lucija Peterlin MašičDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva Cesta 7, 1000 Ljubljana, Slovenia.
Nikola MinovskiTheory Department, Laboratory for Cheminformatics, National Institute of Chemistry, Hajdrihova 19, 1001 Ljubljana, Slovenia.ORCID 0000-0003-0039-2246
Marko AnderluhDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva Cesta 7, 1000 Ljubljana, Slovenia.ORCID 0000-0003-1768-8246
Martina Hrast RambaherDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva Cesta 7, 1000 Ljubljana, Slovenia.ORCID 0000-0003-0488-2445

Funding

Slovenian Research Agency J3-50123Slovenian Research Agency P1-0017Slovenian Research Agency P1-0208
6 · The paper itself

Abstract

backgroundThe novel bacterial topoisomerase inhibitors (NBTIs) developed in our laboratory show potent on-target enzyme inhibition but suffer from low activity against Gram-negative bacteria.

methodsWith the aim of improving the antibacterial activity of our compounds against Gram-negative bacteria, we tested them in combination with different efflux pump inhibitors (EPIs), a strategy that showed promise in several other classes of antimicrobials. We also investigated the combined effect of NBTIs with ATP-competitive inhibitors of bacterial type II topoisomerases (ACIs), as well as the antibiofilm properties of our compounds and the combination with EPIs against early and mature

resultsOur results demonstrate that combinations of NBTIs with EPI Phenylalanine-arginyl-β-naphthylamide significantly reduce the corresponding NBTIs' minimal inhibitory concentration values and show potentiation of

conclusionsThese results show for the first time that combinations of NBTIs with either EPIs or a different class of the topoisomerase inhibitors may be a beneficial strategy to combat difficult-to-treat bacterial infections.

Indexed as

antimicrobial resistancebacterial biofilmsefflux pump inhibitorsESKAPE pathogensNBTIstopoisomerase inhibitors

Identifiers

PMID39596774
PMCPMC11591509

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.