Evidence map›Paper›PMID 39413207›Full record

ArticleNucleic acids research2024

Pathogen-encoded Rum DNA polymerase drives rapid bacterial drug resistance.

Malgorzata M Jaszczur, Phuong Pham, Debika Ojha, Cecilia Q Pham, John P McDonald, Roger Woodgate, Myron F Goodman

Erratum issuedAbstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Interaction of the SXT/R391 element ICEMicrobiology spectrum · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Malgorzata M JaszczurDepartment of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Phuong PhamDepartment of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.ORCID 0000-0002-8802-2188
Debika OjhaDepartment of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Cecilia Q PhamDepartment of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
John P McDonaldLaboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Roger WoodgateLaboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Myron F GoodmanDepartment of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.ORCID 0000-0001-9601-3284

Funding

Creation and Repair of Postreplicative DNA GapsRM1GM130450 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI Michael M. Cox, MYRON GOODMAN · 2019 to 2026
$10.4M
Hypermutation in Bacteria and HumansR35ES028343 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GOODMAN, MYRON · 2017 to 2024
$4.3M
Intramural Research ProgramNational Institutes of Child Health and Human DevelopmentNational Institutes of General Medical Sciences R35ES028343NIEHS NIH HHS R35 ES028343NIEHS NIH HHS R35ES028343NIGMS NIH HHS RM1 GM130450NIH HHS
6 · The paper itself

Abstract

The acquisition of multidrug resistance by pathogenic bacteria is a potentially incipient pandemic. Horizontal transfer of DNA from mobile integrative conjugative elements (ICEs) provides an important way to introduce genes that confer antibiotic (Ab)-resistance in recipient cells. Sizable numbers of SXT/R391 ICEs encode a hypermutagenic Rum DNA polymerase (Rum pol), which has significant homology with Escherichia coli pol V. Here, we show that even under tight transcriptional and post-transcriptional regulation imposed by host bacteria and the R391 ICE itself, Rum pol rapidly accelerates development of multidrug resistance (CIPR, RifR, AmpR) in E. coli in response to SOS-inducing Ab and non-Ab external stressors bleomycin (BLM), ciprofloxacin (CIP) and UV radiation. The impact of Rum pol on the rate of acquisition of drug resistance appears to surpass potential contributions from other cellular processes. We have shown that RecA protein plays a central role in controlling the ability of Rum pol to accelerate antibiotic resistance. A single amino acid substitution in RecA, M197D, acts as a 'Master Regulator' that effectively eliminates the Rum pol-induced Ab resistance. We suggest that Rum pol should be considered as one of the major factors driving development of de novo Ab resistance in pathogens carrying SXT/R391 ICEs.

Indexed as

DNA-Directed DNA PolymeraseEscherichia coliEscherichia coli ProteinsRec A RecombinasesAnti-Bacterial AgentsBleomycinCiprofloxacinDNA-Binding ProteinsDrug Resistance, BacterialDrug Resistance, Multiple, BacterialGene Expression Regulation, BacterialSOS Response, GeneticsUltraviolet RaysAnti-Bacterial AgentsBleomycinCiprofloxacinDNA-Binding ProteinsDNA-Directed DNA PolymeraseEscherichia coli ProteinsrecA protein, E coliRec A RecombinasesUmuD protein, E coli

Identifiers

PMID39413207
PMCPMC11602152

What Socratic holds

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LicenceCC BY-NC
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 Socratic graph.