High throughput screen for inhibitors of fatty acid...

Chemistry: molecular biology and microbiology – Micro-organism – per se ; compositions thereof; proces of... – Bacteria or actinomycetales; media therefor

Reexamination Certificate

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C435S032000, C435S006120, C435S007200, C435S069200

Reexamination Certificate

active

10683482

ABSTRACT:
Methods for identifying compounds that are inhibitors of bacterial fatty acid biosynthesis are disclosed. Such compounds can be used as lead compounds in methods for preparing antibacterial agents for treating bacterial infections (e.g., in humans, animals, and plants). Inhibitors of bacterial fatty acid synthesis can also be tested for their ability to inhibit synthesis of acylated homoserine lactones. Compounds that inhibit synthesis of acylated homoserine lactones can be used as inhibitors of bacterial virulence. The disclosed methods allow for high throughput screening of libraries of test compounds.

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Attachment 1: Sequence Match to SEQ ID #1. US-09-474-140-1.rge; Mon., May 21, 2001.
Attachment 2: Sequence Match to SEQ ID #3. US-09-474-140-3.rge; Mon., May 21, 2001.
Attachment 3:Bacillus subtilispromoters and genes. Accession No. 1997:748948 Caplus.
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Magnuson et al., “Regulation of Fatty Acid Biosynthesis inEscherichia coli”,Microbiological Reviews, vol. 57, No. 3, pp. 552-542 (1993).
McMurry et al., “Triclosan targets lipid synthesis”Nature, vol. 394, pp. 531-532 (1998).
Moche et al., “Structure of the Complex between the Antibiotic Cerulenin and Its Target, β-Ketoacyl-Acyl Carrier Protein Synthase”,Journal of Biological Chemistry, vol. 274, No. 10, pp. 6031-6034 (1999).
Morbidoni et al., “Bacillus subtilisAcyl Carrier Protein Is Encoded in a Cluster of Lipid Biosynthesis Genes”,Journal of Bacteriology, vol. 178, No. 16, pp. 4794-4800 (1996).
Noback et al., “The 172 kb prk A-add-AB region from 83 to 97 of theBacillus subtilischromosome contains several dysfunctional genes, the glyB marker, many genes encoding transporter proteins, and the ubiquitous hit gene,”Microbiology, 144 pp. 859-875 (1998).
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Schujman et al., “De novo fatty acid synthesis is required for establishment of cell type-specific gene transcription during sporulation inBacilius subtilis,”Molecular Microbiology, 29 (5), pp. 1215-1224, 1998.
Val et al., “In Vivo Evidence that S-Adenosylmethionine and Fatty Acid Synthesis Intermediates Are the Substrates for the Luxl Family of Autoinducer Synthases.”Journal of Bacteriology, vol. 180, No. 10, pp. 2644-2651, 1998.
Attachment1: Sequence Match to SEQ ID #1. US-09-474-140-1.rge; Mon., May 21, 2001.
Attachmennt 2: Sequence Match to SEQ ID #3. US-09-474-140-3.rge; Mon., May 21, 2001.
Attachment 3:Bacillus subtilispromoters and genes. Accession No.: 1997:748948 Caplus.

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