# Functional genomics for Chlamydia

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $790,056

## Abstract

PROJECT SUMMARY
For bacterial pathogens, the first studies that begin to define the microorganism’s functional genetic nature on
a genome-wide scale, frequently represent a landmark and highly impactful achievement. The major human
pathogen Chlamydia trachomatis is a bacterium for which such studies have not been performed, in large part
due to Chlamydia’s obligate intracellular nature and historical intractability to modern genetic manipulation.
With the development of two major genetic tools for Chlamydia by our group—transposon mutagenesis and
lateral gene transfer chimeras—functional genomic investigations in Chlamydia are now possible.
Our long term goal is to globally define and functionally characterize the genetic correlates to C. trachomatis
infection and pathogenesis. Using the complementary approaches of transposon mutagenesis and
interspecies chimeras, we propose to: (i) identify the major genetic determinants of Chlamydia infection using a
clinically relevant mouse model and in vitro assays; (ii) determine the Chlamydia genes associated with host
adaptation by exploiting interspecies lateral gene transfer within Chlamydia and the signature host tropisms of
the parental strains; (iii) characterize the mechanisms of host cell subversion by the secreted inclusion
membrane effector proteins IncU and IncS.
These efforts are essential for gaining a functional appreciation of the role that unique chlamydial genes play in
the organism’s growth and development, and also Chlamydia’s evolutionary adaptation to successfully
maintain infection and pathogenesis in complex mammalian hosts. We anticipate that Chlamydia will serve as
a model obligate intracellular bacterium, and, therefore, the knowledge obtained from this work will broadly
extend to other pathogens that have evolved an obligate intracellular niche in their mammalian hosts.
Identification of these loci is critical for our understanding of the mechanisms through which Chlamydia have
adapted to mammalian hosts, and represents an important step towards elucidating the major virulence
correlates of C. trachomatis in humans.

## Key facts

- **NIH application ID:** 10876282
- **Project number:** 5R01AI126785-08
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** P Scott Hefty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $790,056
- **Award type:** 5
- **Project period:** 2017-03-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876282

## Citation

> US National Institutes of Health, RePORTER application 10876282, Functional genomics for Chlamydia (5R01AI126785-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10876282. Licensed CC0.

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