Antibiotic Discovery. Streptomyces

Antibiotic resistance is a growing problem in the U.S. Methicillin-resistant Staphyloccocus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are on the rise, and strains of vancomycin-resistant Staphylococcus aureus (VRSA) have begun to appear. Multi-resistant strains of Klebsiella and Salmonella18, for which there are few effective treatments, are becoming more common in nosocomial settings. Nor is the problem of antimicrobial resistance confined to the hospital; the increasing incidence of S. aureus infections in the community is among the most alarming recent trends. The genome sequences of Streptomyces coelicolor and Streptomyces avermitilis stimulated a great deal of research into the natural products - known and cryptic - produced by these strains, helping spur the development of genetic techniques to modify these organisms and to express genes and gene clusters from this organisms in heterologous hosts. In addition to the work described above that we will perform to characterize the cryptic natural products and biosynthetic enzymes encoded by these strains, we anticipate that the genome sequences of our panel of antibiotic producers will stimulate a much larger effort in the community to mine their genomes for new natural product antibiotics, and will likely lead to the adaptation of existing Streptomyces genetic techniques to the strains we have sequenced. The overlapping fields of Streptomyces genetics and natural product antibiotic discovery stand to benefit tremendously from these sequences.