Virulence determinants in the obligate intracellular pathogen Chlamydia trachomatis revealed by forward genetic approaches.

Published

Journal Article

Chlamydia trachomatis, a pathogen responsible for diseases of significant clinical and public health importance, remains poorly characterized because of its intractability to routine molecular genetic manipulation. We have developed a combinatorial approach to rapidly generate a comprehensive library of genetically defined mutants. Chemical mutagenesis, coupled with whole-genome sequencing (WGS) and a system for DNA exchange within infected cells, was used to generate Chlamydia mutants with distinct phenotypes, map the underlying genetic lesions, and generate isogenic strains. As a result, we identified mutants with altered glycogen metabolism, including an attenuated strain defective for type II secretion. The coupling of chemically induced gene variation and WGS to establish genotype-phenotype associations should be broadly applicable to the large list of medically and environmentally important microorganisms currently intractable to genetic analysis.

Full Text

Duke Authors

Cited Authors

  • Nguyen, BD; Valdivia, RH

Published Date

  • 2012-01-24

Published In

Volume / Issue

  • 109 / 4

Start / End Page

  • 1263 - 1268

PubMed ID

  • 22232666

Pubmed Central ID

  • 22232666

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1117884109

Language

  • eng

Conference Location

  • United States