# The molecular control of bacterial programmed cell death

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2020 · $376,250

## Abstract

Studies of the Staphylococcus aureus cid and lrg operons have provided important
insight into the regulatory control of bacterial murein hydrolase activity and autolysis and have
led to a model in which this system is functionally analogous to the control elements of
programmed cell death (PCD) in more complex eukaryotic organisms. Although the Cid and Lrg
proteins have been shown to be similar to bacteriophage holins and antiholins, respectively,
which are fundamental to the control of cell death and lysis during the lytic stage of a
bacteriophage infection, the precise molecular/biochemical mechanisms utilized by their
bacterial counterparts during cell death and lysis remain to be determined. In the current
proposal, we have built on recent studies in our laboratory demonstrating that cytoplasmic
acidification and pyruvate metabolism are critical aspects of bacterial cell death to probe the
specific functions of the Cid and Lrg proteins. In the first specific aim we will utilize a molecular
genetic approach to examine the relationship between the CidA/B proteins and pyruvate
metabolic enzymes in the control of bacterial cell death. The second aim will utilize a biophysical
approach to test the model that Cid- and Lrg-mediated transport is a fundamental aspect of the
control of bacterial cell death. The third and final aim will explore the CidR-mediated regulation
of this system with a focus on the identification of the effector molecule(s) that induces its
activity. Overall, the results generated by the experiments described in these aims will illuminate
the molecular mechanisms underlying bacterial PCD and uncover the metabolic control
elements required for its regulation, ultimately leading to improved therapeutic strategies to fight
bacterial infections.

## Key facts

- **NIH application ID:** 9901430
- **Project number:** 5R01AI125589-05
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** KENNETH W. BAYLES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $376,250
- **Award type:** 5
- **Project period:** 2016-05-24 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9901430

## Citation

> US National Institutes of Health, RePORTER application 9901430, The molecular control of bacterial programmed cell death (5R01AI125589-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9901430. Licensed CC0.

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