# Analysis of Staphylococcus Aureus Host Interactions.

> **NIH NIH R01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2020 · $631,658

## Abstract

Project Summary
S. aureus is a potent, opportunistic human pathogen that has evolved in a symbiotic relationship with its hosts
and is notorious for its ability to cause life-threatening diseases such as sepsis, pneumonia and endocarditis. In
2005 S. aureus was responsible for more death in the US than any other microbial pathogen. S. aureus is unique
in that the organism produces over a dozen fibrinogen (Fg) binding cell wall anchored proteins (MSCRAMMs) or
small secreted proteins. Many of these proteins act as potent virulence factors and can recruit Fg and assemble
a Fg containing coat surrounding and protecting the bacteria from phagocytosis and clearance. We believe that
this Fg containing shield represents a key to understand the unique features of S. aureus virulence including the
organism’s demonstrated resistance in several active and passive vaccination trials. Consequently, we propose
to characterize the staphylococcal Fg binding proteins, their interactions with Fg and the conformational changes
leading to the formation of the shield. We will use X-ray crystallography of complexes formed between the
bacterial proteins/peptides and Fg fragments/peptides complemented by extensive biochemical studies to
characterize the Fg interactions and determining interactive sites. Preliminary results show that the MSCRAMMs
use a combination of a primary and a secondary synergistic site to bind Fg with high affinity whereas a common
linear Fg binding motif present in two of the secreted proteins exhibits an amazingly high affinity for Fg. The
conformational changes induced in Fg upon binding to different staphylococcal proteins will be identified by
crystallographic analysis of intact Fg in complex with staphylococcal proteins/peptides and further analyzed in a
mouse septicemia model. Based on the detailed information of staphylococcal protein/Fg interactions, we will
identify MSCRAMM variants with altered affinity for Fg and explore the possibility that these exhibit altered
virulence potentials. Finally, with comprehensive knowledge of staphylococcal Fg interactions, we will generate
mAbs that can inhibit Fg binding to staphylococcal proteins. In the future, these mAbs could be developed to
useful therapeutic agents.

## Key facts

- **NIH application ID:** 9828039
- **Project number:** 5R01AI020624-35
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Axel MAGNUS HOOK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $631,658
- **Award type:** 5
- **Project period:** 1989-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828039

## Citation

> US National Institutes of Health, RePORTER application 9828039, Analysis of Staphylococcus Aureus Host Interactions. (5R01AI020624-35). Retrieved via AI Analytics 2026-06-16 from https://api.ai-analytics.org/grant/nih/9828039. Licensed CC0.

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