Systematic, condition-independent identification of essential genes of microorganisms

Summary Traditional antibiotics have been aimed at a small subset of cellular processes (such as cell wall synthesis, protein synthesis and mRNA synthesis) and targets (including DNA gyrase and the cell membrane). Linkage of additional genes, proteins and pathways with functions essential to microbial infectivity is highly desirable, as it may lead to the development of new classes of useful antibiotics.

This invention identifies new antimicrobial targets though high-density mutagenesis of a limited region of the microbial genome followed by examination of that region in surviving cells to detect sites at which induced mutations are absent or reduced in number. While conventional methods only identify genes essential under investigator-determined selective conditions, this invention reveals genes that are required under normal growth conditions and/or under conditions that place stress on previously-unrecognized essential processes. This convenient procedure requires no enrichment step for cells containing induced mutations because of efficient localized mutagenesis. Further, the entire experimental cell population is maintained under a single growth condition, where the distribution of non-lethal mutations is observed in a step that does not require comparison to a control DNA sample.

The invention is protected by U.S. Patent No. 6,207,384 and is available for field-exclusive or non-exclusive license.

Applications Antimicrobial drug development. For Further Information Please Contact the Director of Business Development Alex Szidon Email: [email protected] Telephone: (617) 495-3067

Inventor(s): Mekalanos, John J

Type of Offer: Licensing



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