# Metabolic control of the second messenger cyclic diguanylate: implications to intracellular bacterial pathogens

> **NIH NIH R21** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $237,480

## Abstract

PROJECT SUMMARY
Bacteria exist as single cells in a planktonic state, but they also associate into
multicellular communities known as biofilms. A rise in the intracellular levels of the
second messenger cyclic diguanylate (c-di-GMP) promotes biofilm formation in a wide
range of bacterial species. Thus, understanding the control of c-di-GMP levels is
essential to comprehend the transition between planktonic to biofilm states. Bacteria
harbor diguanylate cyclases and phosphodiesterases, which are enzymes that
synthesize and degrade c-di-GMP, respectively. A given bacterial species often harbors
a large repertoire of these enzymes, each regulating a distinct cellular process. We
reported that a Salmonella enterica serovar Typhimurium strain lacking the mgtC
virulence gene harbors increased levels of c-di-GMP and of cellulose, a major
component of biofilms that inhibits Salmonella replication inside macrophages. We have
now identified the specific diguanylate cyclases responsible for the c-di-GMP-
dependent cellulose synthesis in the mgtC mutant and established that they undergo
post-translational activation. We have also utilized a novel c-di-GMP fluorescence
reporter to select mutations (currently being mapped by high-throughput sequencing)
that affect the activities of these diguanylate cyclases. This proposal seeks to define
how the identified diguanylate cyclases are activated, and to determine the role of
MgtC in controlling crucial physiological functions in Salmonella during infection.
Specifically, the identification of genes controlling these diguanylate cyclases will
enable us to explore how these enzymes are controlled during Salmonella replication
inside macrophages and, by proxy, make testable inferences about metabolic changes
promoted by MgtC. These investigations will reveal the cues promoting c-di-GMP
synthesis and biofilm formation, and how bacterial pathogens must control their
metabolism to replicate in host phagocytic cells.

## Key facts

- **NIH application ID:** 10055808
- **Project number:** 1R21AI148774-01A1
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Mauricio Henriques Pontes
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $237,480
- **Award type:** 1
- **Project period:** 2020-05-21 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055808

## Citation

> US National Institutes of Health, RePORTER application 10055808, Metabolic control of the second messenger cyclic diguanylate: implications to intracellular bacterial pathogens (1R21AI148774-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10055808. Licensed CC0.

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