# Characterization of assembly factors for type IV secretion systems

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2021 · $212,812

## Abstract

Abstract
Many bacterial pathogens employ complex, specialized secretion systems to export toxins and deliver
effectors into the cytoplasm of mammalian cells. Although a significant amount of work has been done on
identifying components of these secretion systems, less is known about the factors that are required for
their assembly/function. We propose to identify and characterize these assembly factors by studying the
type IVB secretion system of Legionella pneumophila. This system, called Dot/Icm, is used by L.
pneumophila to survive and replicate within alveoloar macrophages, thereby mediating a pneumonia-like
disease called Legionnaires’ disease. The L. pneumophila T4BSS is encoded by approximately thirty
dot/icm genes. These genes are essential for intracellular replication and virulence of this pathogen, but
most are not required for growth of the organism on media. However, dotL is an essential gene under all
conditions and a large number of suppressors can be isolated that allow a ∆dotL strain to live. These
suppressors include mutations in other dot/icm genes and in a number of putative assembly factors
including DjlA and LdsA. Based on these observations, we propose to isolate additional ∆dotL lethality
suppressors using Tn-seq and to elucidate how DjlA and LdsA function in the assembly/function of the
Dot/Icm T4BSS. Information acquired will provide insight into how L. pneumophila’s T4BSS assembles
and functions and may reveal novel targets for drug intervention.

## Key facts

- **NIH application ID:** 10288771
- **Project number:** 1R21AI163928-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Joseph P Vogel
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $212,812
- **Award type:** 1
- **Project period:** 2021-06-21 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10288771

## Citation

> US National Institutes of Health, RePORTER application 10288771, Characterization of assembly factors for type IV secretion systems (1R21AI163928-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10288771. Licensed CC0.

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