Evidence map›Paper›PMID 34134705›Full record

ArticleAnnals of clinical microbiology and antimicrobials2021

Role of AmpG in the resistance to β-lactam agents, including cephalosporins and carbapenems: candidate for a novel antimicrobial target.

Roshan D'Souza, Le Phuong Nguyen, Naina A Pinto, Hyunsook Lee, Thao Nguyen Vu, Hoyoung Kim, Hyun Soo Cho, Dongeun Yong

Open access · goldAbstract read
In one paragraph

Article in Annals of clinical microbiology and antimicrobials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.5field-weighted citation impact, top 45% 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

9 citing papers in PubMed, 11 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

8 authors at 1 institution in 2 countries.

Roshan D'Souza *Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
Le Phuong Nguyen *Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
Naina A PintoBrain Korea 21+ Project for Medical Science, Yonsei University, Seoul, Korea.
Hyunsook LeeDepartment of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
Thao Nguyen VuDepartment of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
Hoyoung KimDepartment of Systems Biology, Yonsei University, Seoul, Korea.
Hyun Soo ChoDepartment of Systems Biology, Yonsei University, Seoul, Korea.
Dongeun YongDepartment of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea. deyong@yuhs.ac.
Yonsei University · KR

Funding

Ministry of Science, ICT and Future Planning H-GUARD_2014M3A6B2060509
6 · The paper itself

Abstract

backgroundA complex cascade of genes, enzymes, and transcription factors regulates AmpC β-lactamase overexpression. We investigated the network of AmpC β-lactamase overexpression in Klebsiella aerogenes and identified the role of AmpG in resistance to β-lactam agents, including cephalosporins and carbapenems.

methodsA transposon mutant library was created for carbapenem-resistant K. aerogenes YMC2008-M09-943034 (KE-Y1) to screen for candidates with increased susceptibility to carbapenems, which identified the susceptible mutant derivatives KE-Y3 and KE-Y6. All the strains were subjected to highly contiguous de novo assemblies using PacBio sequencing to investigate the loss of resistance due to transposon insertion. Complementation and knock-out experiments using lambda Red-mediated homologous recombinase and CRISPR-Cas9 were performed to confirm the role of gene of interest.

resultsIn-depth analysis of KE-Y3 and KE-Y6 revealed the insertion of a transposon at six positions in each strain, at which truncation of the AmpG permease gene was common in both. The disruption of the AmpG permease leads to carbapenem susceptibility, which was further confirmed by complementation. We generated an AmpG permease gene knockout using lambda Red-mediated recombineering in K. aerogenes KE-Y1 and a CRISPR-Cas9-mediated gene knockout in multidrug-resistant Klebsiella pneumoniae-YMC/2013/D to confer carbapenem susceptibility.

conclusionsThese findings suggest that inhibition of the AmpG is a potential strategy to increase the efficacy of β-lactam agents against Klebsiella aerogenes.

Indexed as

Amino Acid SequenceAnti-Bacterial AgentsBacterial Proteinsbeta-Lactam Resistancebeta-LactamsCarbapenemsCephalosporinsCRISPR-Cas SystemsDemocratic People's Republic of KoreaDNA Transposable ElementsGene Expression Regulation, BacterialGene Knockout TechniquesHumansKlebsiella pneumoniaeMembrane Transport ProteinsMicrobial Sensitivity TestsAmpG protein, BacteriaAnti-Bacterial AgentsBacterial Proteinsbeta-LactamsCarbapenemsCephalosporinsDNA Transposable ElementsMembrane Transport ProteinsAmpGCarbapenem resistanceCRISPR–Cas9

Identifiers

PMID34134705
PMCPMC8207665
OpenAlexW3170589284

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.