# Using phage to interrogate bacterial heterochromatin

> **NIH NIH DP2** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $2,662,500

## Abstract

Project Abstract:
In most environments including the human host in the context of chronic infections, bacteria often
face starvation and are not actively growing. Starved bacteria are intrinsically tolerant to conventional
antibiotics that target activities important for growth but dispensable for starvation, such as DNA
replication and cell wall biosynthesis. There is a pressing need, therefore, to understand activities that
are important to bacteria for starvation survival. One widely conserved starvation response in bacteria
is to globally remodel and compact the chromosome in order to silence transcription and protect the
chromosome from damage due to environmental insults when resources may become limited. A key
structural protein bacteria use to silence and protect DNA is called H-NS. H-NS can oligomerize on
the chromosome to form large regions of silenced, compacted DNA, the bacterial functional analogue
to eukaryotic chromatin. Bacteria also use H-NS to combat phage, by silencing phage DNA. Bacterial
heterochromatin is therefore an important battleground in the arms race between phage and their
bacterial hosts. The core strategy of this proposal is to exploit phage to learn about bacterial
heterochromatin in the opportunistic human pathogen Pseudomonas aeruginosa. Understanding of
how phage fights against heterochromatin silencing by its host has the potential to provide inspiration
for novel antimicrobial therapies that target starved bacteria.

## Key facts

- **NIH application ID:** 10003069
- **Project number:** 1DP2GM140918-01
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Lisa R Racki
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,662,500
- **Award type:** 1
- **Project period:** 2020-09-30 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003069

## Citation

> US National Institutes of Health, RePORTER application 10003069, Using phage to interrogate bacterial heterochromatin (1DP2GM140918-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10003069. Licensed CC0.

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