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Related Experiment Video

Updated: May 14, 2026

Mapping Bacterial Functional Networks and Pathways in Escherichia Coli using Synthetic Genetic Arrays
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Published on: November 12, 2012

Combining functional and structural genomics to sample the essential Burkholderia structome.

Loren Baugh1, Larry A Gallagher, Rapatbhorn Patrapuvich

  • 1Seattle Structural Genomics Center for Infectious Disease, Seattle, Washington, United States of America.

Plos One
|February 6, 2013
PubMed
Summary

Researchers identified essential genes in Burkholderia and determined protein structures for antimicrobial drug target discovery. This structural genomics approach provides a resource for developing new drugs against Burkholderia infections.

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Area of Science:

  • Microbiology
  • Structural Biology
  • Drug Discovery

Background:

  • The genus Burkholderia harbors pathogenic bacteria responsible for serious infections like melioidosis and glanders.
  • Increasing antimicrobial resistance necessitates the development of novel therapeutic strategies.
  • High-resolution protein structures are crucial for structure-based drug design against essential bacterial targets.

Purpose of the Study:

  • To identify essential genes within Burkholderia species.
  • To determine the high-resolution structures of essential proteins for antimicrobial drug target identification.
  • To create a structural genomics resource for developing new drugs against Burkholderia infections.

Main Methods:

  • Saturation-level transposon mutagenesis and next-generation sequencing (Tn-seq) were employed to identify 406 putative essential genes in B. thailandensis.
  • A structural genomics pipeline was utilized to determine protein structures, incorporating an 'ortholog rescue' strategy for challenging targets.
  • 88 protein structures were deposited into the Protein Data Bank (PDB), covering 49 essential gene families.

Main Results:

  • 406 putative essential genes were identified in B. thailandensis.
  • 88 protein structures were determined and deposited, including 31 from B. thailandensis and 25 orthologs from other Burkholderia species.
  • 25 proteins were identified as potential antimicrobial drug targets based on criteria including lack of human homologs and presence of deep binding pockets.

Conclusions:

  • The study provides a valuable collection of structural, solubility, and essentiality data for Burkholderia proteins.
  • This resource facilitates the development of novel drugs targeting essential pathways in Burkholderia species.
  • All expression clones and proteins are available for research purposes.