Evidence map›Paper›PMID 38413891›Full record

ArticleBMC microbiology2024

Phenotypic, molecular, and in silico characterization of coumarin as carbapenemase inhibitor to fight carbapenem-resistant Klebsiella pneumoniae.

Mahmoud Saad Abdel-Halim, Amira M El-Ganiny, Basem Mansour, Galal Yahya, Hemat K Abd El Latif, Momen Askoura

Open access · goldAbstract read
In one paragraph

Article in BMC microbiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.2field-weighted citation impact, top 25% of its field
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

3 citing papers in PubMed, 7 citations in OpenAlex.

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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

6 authors at 2 institutions in 1 country.

Mahmoud Saad Abdel-HalimMicrobiology and Immunology Department, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt. mahmoudsaad@zu.edu.eg.ORCID 0000-0002-3944-8465
Amira M El-GaninyMicrobiology and Immunology Department, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Basem MansourPharmaceutical Chemistry Department, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt.
Galal YahyaMicrobiology and Immunology Department, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Hemat K Abd El LatifMicrobiology and Immunology Department, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Momen AskouraMicrobiology and Immunology Department, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Zagazig University · EGDelta University for Science and Technology · EG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCarbapenems represent the first line treatment of serious infections caused by drug-resistant Klebsiella pneumoniae. Carbapenem-resistant K. pneumoniae (CRKP) is one of the urgent threats to human health worldwide. The current study aims to evaluate the carbapenemase inhibitory potential of coumarin and to test its ability to restore meropenem activity against CRKP. Disk diffusion method was used to test the antimicrobial susceptibility of K. pneumoniae clinical isolates to various antibiotics. Carbapenemase genes (NDM-1, VIM-2, and OXA-9) were detected using PCR. The effect of sub-MIC of coumarin on CRKP isolates was performed using combined disk assay, enzyme inhibition assay, and checkerboard assay. In addition, qRT-PCR was used to estimate the coumarin effect on expression of carbapenemase genes. Molecular docking was used to confirm the interaction between coumarin and binding sites within three carbapenemases.

resultsK. pneumoniae clinical isolates were found to be multi-drug resistant and showed high resistance to meropenem. All bacterial isolates harbor at least one carbapenemase-encoding gene. Coumarin significantly inhibited carbapenemases in the crude periplasmic extract of CRKP. The checkerboard assay indicated that coumarin-meropenem combination was synergistic exhibiting a fractional inhibitory concentration index ≤ 0.5. In addition, qRT-PCR results revealed that coumarin significantly decreased carbapenemase-genes expression. Molecular docking revealed that the binding energies of coumarin to NDM1, VIM-2, OXA-48 and OXA-9 showed a free binding energy of -7.8757, -7.1532, -6.2064 and - 7.4331 Kcal/mol, respectively.

conclusionCoumarin rendered CRKP sensitive to meropenem as evidenced by its inhibitory action on hydrolytic activity and expression of carbapenemases. The current findings suggest that coumarin could be a possible solution to overcome carbapenems resistance in CRKP.

Indexed as

Klebsiella InfectionsKlebsiella pneumoniaeAnti-Bacterial AgentsBacterial Proteinsbeta-LactamasesCarbapenemsCoumarinsHumansMeropenemMicrobial Sensitivity TestsMolecular Docking SimulationAnti-Bacterial AgentsBacterial Proteinsbeta-LactamasescarbapenemaseCarbapenemsCoumarinsMeropenemCarbapenem-resistantCheckerboard assayCoumarinKlebsiella pneumoniaeMolecular dockingqRT-PCR

Identifiers

PMID38413891
PMCPMC10898048
OpenAlexW4392190501

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.