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IU to Study Chlamydia's Genome to Learn its Evasive Tactics

NEW YORK (GenomeWeb News) – Indiana University researchers will use a $2.3 million National Institutes of Health grant to fund a study that will employ a range of genomics techniques to discover how the Chlamydia trachomatis bacterium evades human immune responses.

The IU Department of Biology team plans to mutate and characterize the functions of certain genes in the pathogen that enable it to remain protected within human and animal cells and which prevents researchers from using standard genetic manipulation techniques to study and combat the parasite.

The researchers, led by Assistant Professor David Nelson, will use a technique called targeted-induced local lesions in genomes to explore genes that may determine which types of hosts and tissues that different Chlamydia species infect. Much of the genetic variation in the disease-causing strains of Chlamydia appears to inhabit a genomic region called the plasticity zone, and that is where the team plans to focus its study.

"With these new tools we can use a reverse genetic approach to inactivate plasticity zone genes and then test to see if the mutants that we've created have certain sensitivities or have alterations in pathogenicity," Nelson said in a statement. "One of our suspicions is that PZ genes counteract host cell proteins that mediate immunity."

The IU group will use genome sequencing, genetic screens, lateral gene transfer, and other approaches to identify those genes that enable Chlamydia strains to dodge its host's immune responses and to understand why host's defenses are sensitive to the infection.

"In the long term we hope our work provides clues toward designing a vaccine and developing strong models of human chlamydial disease," Nelson added. "But most immediately we're looking to identify and characterize the factors that allow this pathogen to grow, how it interacts with other bacteria, and how it avoids host immune systems so well."

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