# Molecular mechanism of metabolic adaptation by Staphylococcus aureus

> **NIH NIH P20** · MISSISSIPPI STATE UNIVERSITY · 2021 · $290,314

## Abstract

PROJECT SUMMARY
Staphylococcus aureus is a versatile pathogen that can colonize the skin and mucous membranes of mammals
without causing symptoms, but it can suddenly produce a life-threatening infection. The mechanism by which
this transition occurs is not known. Staphylococcus aureus accounts for 300,000 hospitalizations and 11,000
deaths annually, resulting in direct heath care costs of more than $4.5 billion in the United States. The successful
pathogenicity of S. aureus may be due to its ability to adapt to different metabolic environments, and it is possible
that differences in the metabolic environment in a particular host may cause a transition of these bacteria from
a non-pathogenic status to a highly pathogenic status. Regulation of the expression of virulence factors is
important to S. aureus for survival, growth, and pathogenicity. The most prominent virulence factors of S. aureus
are staphylococcal exotoxins (cytotoxins and enterotoxins) that disarm the host immune system by causing lysis
of leukocytes or aberrant activation of immune system cells, leading to shock. Another important virulence factor
is alteration of bacterial cell wall structures that confers evasion from host immune surveillance and resistance
to antibiotics. Metabolism is an integral process by which nutrients are assimilated into energy and biomass.
Considerable evidence indicates that metabolic adaptation to local nutrient availability can greatly affect the
pathogenicity of S. aureus by altering expression of key virulence factors. However, very little is known about
the role of particular carbon sources (carbohydrates) in the pathogenicity of S. aureus or the underlying
regulatory networks linking metabolism and pathogenicity. Our long-term goal is to determine the molecular
mechanisms by which metabolic adaptation by S. aureus increases virulence and antibiotic resistance. Our
central hypothesis is that the expression of specific virulence factors is linked to the metabolism of specific
carbohydrates and that this process is regulated by carbon catabolite repression (CCR) pathways.
 This will be investigated by pursuing the following specific aims: 1) Determine the effect of particular
carbohydrates on alteration of S. aureus pathogenicity and antibiotic resistance, and 2) Determine the role of
carbon catabolite repression in metabolic adaptation of S. aureus. We expect this study to lead to identification
of specific carbohydrate-driven changes in the molecular architecture of the cell wall of S. aureus which
decreases recognition by innate immune cells and increases resistance to antibiotic. It is also expected that this
study will reveal key metabolic intermediates regulating in metabolic adaptation which may be exploited
pharmaceutically to develop novel therapies against S. aureus.

## Key facts

- **NIH application ID:** 10261571
- **Project number:** 5P20GM103646-09
- **Recipient organization:** MISSISSIPPI STATE UNIVERSITY
- **Principal Investigator:** Joo Youn Park
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $290,314
- **Award type:** 5
- **Project period:** 2013-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10261571

## Citation

> US National Institutes of Health, RePORTER application 10261571, Molecular mechanism of metabolic adaptation by Staphylococcus aureus (5P20GM103646-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10261571. Licensed CC0.

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