# Dissecting a sensory system for Legionella replication vacuole integrity

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2024 · $245,625

## Abstract

PROJECT SUMMARY
 Infectious disease is a major threat to human health worldwide. The emergence of
antibiotic resistance pathogens necessitates the development of new drugs to treat infections. A
fundamental challenge in developing antibiotics is that many pathogens replicate inside host
cells rendering them inaccessible to antimicrobial agents. The critical processes that govern
pathogen growth within host cells represent promising new targets for therapeutic intervention.
 Pathogens encounter a broad assortment of challenges within the host. The ability to
perceive and adapt to these challenges is a critical determinant of virulence. These adaptations
are mediated by sensory systems that detect host-imposed insult or alterations in their local
environment and drive an appropriate response. Many bacterial pathogens that grow inside host
cells do so in specialized compartments called replication vacuoles. Maintaining the integrity of
the replication vacuole is paramount to bacterial survival and growth as it provides protection
against host surveillance systems that detect and eliminate pathogens. Disrupting this process
would thus limit bacterial burden and enable pathogen killing by the host. Despite vacuole
integrity being paramount for pathogenesis, the mechanisms responsible and how bacteria
sense and respond to defects in this process are poorly understood.
 We have identified a cell-surface signaling system employed by the bacterial pathogen
Legionella that plays a central role in promoting vacuole integrity. Legionella is the causative
agent of a life-threatening pneumonia called Legionnaire’s disease and a world-wide health
problem. The goal of this research is to characterize how signals are propagated and the
response pathway that compensates ensures vacuole stability. This work will define an
unprecedented molecular surveillance system employed by a vacuolar pathogen to sustain its
replication compartment and thus, a new paradigm in microbial pathogenesis. As vacuole
integrity plays is a central role in defining the virulence of numerous intracellular pathogens, this
work will have broad implications across the field of microbial pathogenesis. This work will
provide unprecedented insight into a critical event that determines the outcome of an infection
and a means to develop new strategies to treat disease.

## Key facts

- **NIH application ID:** 10987109
- **Project number:** 1R21AI180914-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Tamara O'Connor
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $245,625
- **Award type:** 1
- **Project period:** 2024-05-22 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10987109

## Citation

> US National Institutes of Health, RePORTER application 10987109, Dissecting a sensory system for Legionella replication vacuole integrity (1R21AI180914-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10987109. Licensed CC0.

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