Evidence map›Paper›PMID 22470465›Full record

ArticlePloS one2012

Exploiting adaptive laboratory evolution of Streptomyces clavuligerus for antibiotic discovery and overproduction.

Pep Charusanti, Nicole L Fong, Harish Nagarajan, Alban R Pereira, Howard J Li, Elisa A Abate, Yongxuan Su, William H Gerwick, Bernhard O Palsson

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
7.8field-weighted citation impact, top 2% 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

40 citing papers in PubMed, 95 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Overview on Strategies and Assays for Antibiotic Discovery.Pharmaceuticals (Basel, Switzerland) · 2022
    Review
  9. Evolving antibiotic spectrum.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  10. Article
  11. Article
  12. Streptomyces clavuligerus: The Omics Era.Journal of industrial microbiology & biotechnology · 2021
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article
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

9 authors at 2 institutions in 1 country.

Pep CharusantiDepartment of Bioengineering, University of California San Diego, La Jolla, California, United States of America.
Nicole L Fong
Harish Nagarajan
Alban R Pereira
Howard J Li
Elisa A Abate
Yongxuan Su
William H Gerwick
Bernhard O Palsson
University of California, San Diego · USScripps Institution of Oceanography · US

Funding

Testable in silico Hypotheses for E.coli GrowthR01GM062791 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PALSSON, BERNHARD O · 2002 to 2009
$4.4M
A Genome-Scale Regulated Metabolic Model of YeastR01GM071808 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PALSSON, BERNHARD O · 2004 to 2007
$2.3M
NIGMS NIH HHS GM062791NIGMS NIH HHS GM071808NIGMS NIH HHS R01 GM062791NIGMS NIH HHS R01 GM071808
6 · The paper itself

Abstract

Adaptation is normally viewed as the enemy of the antibiotic discovery and development process because adaptation among pathogens to antibiotic exposure leads to resistance. We present a method here that, in contrast, exploits the power of adaptation among antibiotic producers to accelerate the discovery of antibiotics. A competition-based adaptive laboratory evolution scheme is presented whereby an antibiotic-producing microorganism is competed against a target pathogen and serially passed over time until the producer evolves the ability to synthesize a chemical entity that inhibits growth of the pathogen. When multiple Streptomyces clavuligerus replicates were adaptively evolved against methicillin-resistant Staphylococcus aureus N315 in this manner, a strain emerged that acquired the ability to constitutively produce holomycin. In contrast, no holomycin could be detected from the unevolved wild-type strain. Moreover, genome re-sequencing revealed that the evolved strain had lost pSCL4, a large 1.8 Mbp plasmid, and acquired several single nucleotide polymorphisms in genes that have been shown to affect secondary metabolite biosynthesis. These results demonstrate that competition-based adaptive laboratory evolution can constitute a platform to create mutants that overproduce known antibiotics and possibly to discover new compounds as well.

Indexed as

Biological EvolutionAnti-Bacterial AgentsBacterial ProteinsDrug Resistance, BacterialGenome, BacterialLactamsMethicillin-Resistant Staphylococcus aureusPlasmidsPolymorphism, Single NucleotideStreptomycesAnti-Bacterial AgentsBacterial ProteinsholomycinLactams

Identifiers

PMID22470465
PMCPMC3312335
OpenAlexW1967709900

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.