Evidence map›Paper›PMID 26711761›Full record

ArticleAntimicrobial agents and chemotherapy2015

Exploring Synergy between Classic Mutagens and Antibiotics To Examine Mechanisms of Synergy and Antibiotic Action.

Lisa Yun Song, Sara D'Souza, Karen Lam, Tina Manzhu Kang, Pamela Yeh, Jeffrey H Miller

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2015. 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 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 22% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Lisa Yun SongDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Sara D'SouzaDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Karen LamDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Tina Manzhu KangDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Pamela YehDepartment of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, California, USA jhmiller@microbio.ucla.edu pamelayeh@ucla.edu.
Jeffrey H MillerDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA jhmiller@microbio.ucla.edu pamelayeh@ucla.edu.
University of California, Los Angeles · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We used classical mutagens in Gram-negative Escherichia coli to study synergies with different classes of antibiotics, test models of antibiotic mechanisms of action, and examine the basis of synergy. We used 4-nitroquinoline 1-oxide (4NQO), zebularine (ZEB), 5-azacytidine (5AZ), 2-aminopurine (2AP), and 5-bromodeoxyuridine (5BrdU) as mutagens (with bactericidal potency of 4NQO > ZEB > 5AZ > 2AP > 5BrdU) and vancomycin (VAN), ciprofloxacin (CPR), trimethoprim (TMP), gentamicin (GEN), tetracycline (TET), erythromycin (ERY), and chloramphenicol (CHL) as antibiotics. We detected the strongest synergies with 4NQO, an agent that oxidizes guanines and ultimately results in double-strand breaks when paired with the bactericidal antibiotics VAN, TMP, CPR, and GEN, but no synergies with the bacteriostatic antibiotics TET, ERY, and CHL. Each of the other mutagens displays synergies with the bactericidal antibiotics to various degrees that reflect their potencies, as well as with some of the other mutagens. The results support recent models showing that bactericidal antibiotics kill bacteria principally by ultimately generating more double-strand breaks than can be repaired. We discuss the synergies seen here and elsewhere as representing dose effects of not the proximal target damage but rather the ultimate resulting double-strand breaks. We also used the results of pairwise tests to place the classic mutagens into functional antibacterial categories within a previously defined drug interaction network.

Indexed as

Drug Synergism2-Aminopurine4-Nitroquinoline-1-oxideAnti-Bacterial AgentsAzacitidineBromodeoxyuridineChloramphenicolCiprofloxacinCytidineDNA Breaks, Double-StrandedErythromycinEscherichia coliGentamicinsMicrobial Sensitivity TestsMutagensTetracycline2-Aminopurine4-Nitroquinoline-1-oxideAnti-Bacterial AgentsAzacitidineBromodeoxyuridineChloramphenicolCiprofloxacinCytidineErythromycinGentamicinsMutagenspyrimidin-2-one beta-ribofuranosideTetracyclineTrimethoprimVancomycin

Identifiers

PMID26711761
PMCPMC4775987
OpenAlexW2297084146

What OpenQuestion holds

Textmetadata
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.