# Computational Studies of the Molecular Basis of Natural and Acquired Resistance to Extremes in Microbes

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 2020 · $291,553

## Abstract

PROJECT SUMMARY
 Our long-term goal is to understand how microbes are able to withstand remarkable extremes of
temperature, pressure, and chemical composition (P-T-X), by determining how the macromolecular
structures comprising the microbes are preserved. Our focus is on effects of high pressure, which are much
less understood than temperature effects. Since high-pressure methods are increasingly being used for
sterilization and food preservation, understanding the limits of pressure is important for human health and
welfare. A disturbing finding is that some mesophilic microbes appear to able to withstand ~10 kbar
pressures, while “piezophiles”, microbes that thrive at high pressures, have been found at maximum
pressures of only ~1.1 kbar. Thus, an overall aim is to help define the limiting pressures that microbes can
endure and recover from upon return to normal conditions, which is relevant to determining whether
pathogenic microbes can survive high pressure treatments, by determining what pressures will permanently
disrupt structures of proteins in the intracellular environment.
 Our over-arching question for the proposed work is how mesophiles can rapidly develop 10 kbar
resistance given that piezophiles have been found only at 1.1 kbar. Our hypotheses are that enzymes from
piezophiles are actually more stable at high pressure than those from mesophiles and that piezolytes
(osmolytes up-regulated by microbes in response to pressure) may further protect enzymes from high
pressure. In particular, piezolytes could lead to rapidly acquired pressure resistance for the entire organism.
 Our specific aims are:
Aim 1. To test existing force fields for a range of P and T and to develop new force fields if needed.
Aim 2. To determine the effects of the flexibility-stability balance on enzymes from mesophiles and
piezophiles at ultra-high P.
Aim 3. To determine the effects of piezolytes on enzymes at ultra-high P.

## Key facts

- **NIH application ID:** 9856312
- **Project number:** 5R01GM122441-04
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Toshiko Ichiye
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $291,553
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856312

## Citation

> US National Institutes of Health, RePORTER application 9856312, Computational Studies of the Molecular Basis of Natural and Acquired Resistance to Extremes in Microbes (5R01GM122441-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9856312. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*