# Quantitative analysis of growth in a streamlined obligate intracellular pathogen

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2021 · $188,750

## Abstract

Members of the Spotted Fever Group (SFG) of the bacterial genus Rickettsia are obligate intracellular pathogens
that cause spotted fever disease in humans ranging from mild to life-threatening. Like all species in the order
Rickettsiales, SFG bacteria have undergone genome streamlining and are dependent on a eukaryotic host for
dozens of essential metabolites. Notably, reductive evolution has led to loss or modification of factors in
metabolic and morphogenetic pathways predicted to impact peptidoglycan cell wall metabolism. Peptidoglycan
metabolism is essential for growth and viability and is therefore an effective antibiotic target. The impact of
genome streamlining on the mechanisms of growth and division of the Rickettsiales, as compared to their free-
living relatives, is not clear. This gap in knowledge persists, in part, because we lack tools to investigate growth
of intracellular bacteria with sufficient resolution to derive a mechanistic understanding. We hypothesize that
reductive evolution of metabolic and morphogenetic pathways necessitates diversification of known mechanisms
to support intracellular growth. In this proposal, we aim to develop and apply methods to quantitatively analyze
growth and cell wall metabolism of Rickettsia parkeri in eukaryotic host cells. R. parkeri is a SFG organism that
causes relatively mild disease. As such, it is a BSL2 pathogen that has been studied as a representative to
understand SFG pathogenesis. Through the proposed work, we will expand the study of R. parkeri to investigate
its intracellular growth mechanisms. In aim 1, we will develop and apply imaging methods to quantitatively
analyze the cell shape of, subcellular protein distribution in, cell cycle status of, and kinetics of growth of individual
R. parkeri in the cytoplasm of eukaryotic host cells. In aim 2, we will determine the chemical composition of and
spatial patterning of peptidoglycan cell wall metabolism of R. parkeri growing in the host cytoplasm. Completion
of the proposed aims will provide foundational knowledge on the growth kinetics and mechanisms of PG
metabolism of a tick-borne, obligate intracellular human pathogen and establish broadly applicable quantitative
approaches for studying growth of bacteria within a eukaryotic host cell. Ultimately, the information and methods
derived from this project will inform development of preventive and therapeutic strategies for limiting Rickettsial
disease.

## Key facts

- **NIH application ID:** 10188728
- **Project number:** 1R21AI159075-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Erin D Goley
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $188,750
- **Award type:** 1
- **Project period:** 2021-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188728

## Citation

> US National Institutes of Health, RePORTER application 10188728, Quantitative analysis of growth in a streamlined obligate intracellular pathogen (1R21AI159075-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10188728. Licensed CC0.

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