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Antibiotic Dereplication Using the Antibiotic Resistance Platform
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New approaches to antimicrobial discovery.

Kim Lewis1

  • 1Department of Biology and Antimicrobial Discovery Center, Northeastern University, Boston, MA 02115, United States.

Biochemical Pharmacology
|November 9, 2016
PubMed
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The rise of antibiotic-resistant bacteria necessitates new drug discovery. Exploring uncultured microbes and genomic data offers promising avenues to revive natural product antibiotic discovery and combat health crises.

Keywords:
ActinomycetesAntibiotic resistanceChronic infectionsPathogens

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Area of Science:

  • Microbiology
  • Drug Discovery
  • Biotechnology

Background:

  • The increasing prevalence of antibiotic-resistant organisms poses a significant global health threat, exacerbated by chronic infections involving antibiotic-tolerant persister cells.
  • The traditional source of antibiotics, soil Actinomycetes, has been overexploited, and synthetic compound libraries have largely failed to yield new drugs due to bacterial permeability barriers.

Purpose of the Study:

  • To address the crisis of antibiotic resistance by reviving natural product discovery.
  • To establish a knowledge base for antimicrobial penetration to guide rational drug design.
  • To explore novel sources of antibiotics from uncultured bacteria and genomic data.

Main Methods:

  • Developing methods to culture previously uncultured bacteria.
  • Utilizing genome sequencing to identify potential antibiotic-producing operons.
  • Employing high-throughput screening of transcription profiles from active extracts to identify novel compounds.

Main Results:

  • Promising compounds are emerging from the cultivation of previously uncultured bacterial species.
  • Genomic analysis reveals a vast, untapped potential for antibiotic discovery within known microbial producers.
  • High-throughput transcription profiling can accelerate the identification of novel natural products.

Conclusions:

  • Reviving natural product discovery from uncultured microbes and genomic data is crucial for combating antibiotic resistance.
  • Establishing rules for antimicrobial penetration will enable the design of effective synthetic libraries.
  • A multi-pronged approach combining cultivation, genomics, and advanced screening is needed to replenish the antibiotic pipeline.