Evidence map›Paper›PMID 36012441›Full record

ArticleInternational journal of molecular sciences2022

Resensitization of Fosfomycin-Resistant

Haniel Siqueira Mortagua Walflor, Aline Rodrigues Castro Lucena, Felipe Francisco Tuon, Lia Carolina Soares Medeiros, Helisson Faoro

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.0field-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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Engineering probioticApplied and environmental microbiology · 2024
    Article
  8. CRISPR-Cas System: A New Dawn to Combat Antibiotic Resistance.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
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

5 authors at 2 institutions in 1 country.

Haniel Siqueira Mortagua WalflorLaboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Fiocruz, Curitiba 81350-010, PR, Brazil.ORCID 0000-0002-9183-702X
Aline Rodrigues Castro LucenaLaboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Fiocruz, Curitiba 81350-010, PR, Brazil.
Felipe Francisco TuonLaboratory of Emerging Infectious Diseases, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, PR, Brazil.ORCID 0000-0003-3471-1786
Lia Carolina Soares MedeirosLaboratory of Cell Biology, Carlos Chagas Institute, Fiocruz, Curitiba 81350-010, PR, Brazil.ORCID 0000-0001-9390-9157
Helisson FaoroLaboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Fiocruz, Curitiba 81350-010, PR, Brazil.
Fundação Carlos Chagas · BRPontifícia Universidade Católica do Paraná · BR

Funding

National Council for Scientific and Technological Development 424410/2018-4Oswaldo Cruz Foundation VPPCB- 07-FIO-18-2-38
6 · The paper itself

Abstract

Antimicrobial resistance is a public health burden with worldwide impacts and was recently identified as one of the major causes of death in 2019. Fosfomycin is an antibiotic commonly used to treat urinary tract infections, and resistance to it in Enterobacteriaceae is mainly due to the metalloenzyme FosA3 encoded by the fosA3 gene. In this work, we adapted a CRISPR-Cas9 system named pRE-FOSA3 to restore the sensitivity of a fosA3+ Escherichia coli strain. The fosA3+ E. coli strain was generated by transforming synthetic fosA3 into a nonpathogenic E. coli TOP10. To mediate the fosA3 disruption, two guide RNAs (gRNAs) were selected that used conserved regions within the fosA3 sequence of more than 700 fosA3+ E. coli isolates, and the resensitization plasmid pRE-FOSA3 was assembled by cloning the gRNA into pCas9. gRNA_195 exhibited 100% efficiency in resensitizing the bacteria to fosfomycin. Additionally, the edited strain lost the ampicillin resistance encoded in the same plasmid containing the synthetic fosA3 gene, despite not being the CRISPR-Cas9 target, indicating plasmid clearance. The in vitro analysis presented here points to a path that can be explored to assist the development of effective alternative methods of treatment against fosA3+ bacteria.

Indexed as

Escherichia coli InfectionsFosfomycinAnti-Bacterial Agentsbeta-LactamasesDrug Resistance, BacterialEscherichia coliHumansMicrobial Sensitivity TestsPlasmidsRNA, Guide, CRISPR-Cas SystemsAnti-Bacterial Agentsbeta-LactamasesFosfomycinRNA, Guide, CRISPR-Cas SystemsCRISPR–Cas9fosA3fosfomycin resistance

Identifiers

PMID36012441
PMCPMC9409345
OpenAlexW4291926518

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.