Antimicrobial Discovery - Project Description
Antimicrobial resistance poses an increasingly serious threat to public health in the U.S. The incidence of resistant pathogens in hospitals and in the community is on the rise, and infections for which no effective antibiotics are available are increasingly common. For these reasons and others, the NIAID has made antimicrobial resistance a Category C priority area.
We propose to use microbial genome sequencing to find solutions to the problem of antibiotic resistance. Most clinically-used antibiotics are based on "natural products" - small molecules produced by microbes for interspecies competition. Recent estimates based on the genome sequences of Streptomyces avermitilis, Streptomyces coelicolor, and Saccharopolyspora erythraea suggest that conventional screening efforts have only found 10-20% of the antibiotics produced by the screened strains. We suggest that these "cryptic" antibiotics are among the most promising source of new drugs to combat antibiotic resistance, and we propose a sequencing-based strategy to help gain access to them.
We are sequencing the genomes of twenty antibiotic-producing bacteria from the order Actinomycetales, which is known for its prolific small molecule production and has been the source of two-thirds of known antibiotics. These data will provide the foundation for our efforts to define and develop the bioinformatic, genetic, and chemical methods needed to discover the cryptic antibiotics that have been overlooked by years of classical screening.
What is Streptomyces?
The genus Streptomyces includes high-GC Gram-positive bacteria from an order known for its prolific production of small molecule natural products, Actinomycetales. Actinomycetes are the source of numerous clinically-used antibiotics, anticancer agents, and immunosuppressive agents.
Photo Captions and Credits
The images on the home page are, from left to right:
- This 1961 photograph depicts a Petri dish in which a colony of Streptomyces somaliensis fungal-like, aerobic bacterial organisms were being cultivated. The particular specie being grown here, S. somaliensis, are found in Africa, the Americas, Israel and India. Public Health Image Library, Dr. Ajello at CDC
- A slide culture of a Streptomyces sp. grown on tap water agar. Branching filaments, abundant aerial mycelia, and long chains of small spores are visible, which is characteristic of all Streptomyces spp.. Public Health Image Library, Dr. David Berd at CDC
- Close-up view of 2.
- Aerial mycelium and spore of Streptomyces coelicolor. The mycelium and the oval spores are about 1?m wide, typical for bacteria and much smaller than fungal hyphae and spores. (Scanning electron micrograph, Mark Buttner, Kim Findlay, John Innes Center)
- An actinomycotic mycetomatous granule due to the bacteria Streptomyces somaliensis. Public Health Image Library, CDC.
This sequencing project was supported by the National Institute of Allergy and Infectious Disease, National Institutes of Health funded Genome Sequencing Center for Infectious Diseases at the Broad Institute.