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Updated: Jun 23, 2026

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
The SaeR/S gene regulatory system is essential for innate immune evasion by Staphylococcus aureus
Jovanka M Voyich1, Cuong Vuong, Mark DeWald
1Department of Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717, USA. jovanka@montana.edu
Abstract:
Methicillin-resistant Staphylococcus aureus is problematic both in hospitals and in the community. Currently, we have limited understanding of mechanisms of innate immune evasion used by S. aureus. To that end, we created an isogenic deletion mutant in strain MW2 (USA400) of the saeR/S 2-component gene regulatory system and studied its role in mouse models of pathogenesis and during human neutrophil interaction. In this study, we demonstrate that saeR/S plays a distinct role in S. aureus pathogenesis and is vital for virulence of MW2 in a mouse model of sepsis. Moreover, deletion of saeR/S significantly impaired survival of MW2 in human blood and after neutrophil phagocytosis. Microarray analysis revealed that SaeR/S of MW2 influences expression of a wide variety of genes with diverse biological functions. These data provide new insight into how virulence is regulated in S. aureus and associates a specific staphylococcal gene-regulatory system with invasive staphylococcal disease.
Insights
The staphylococcal saeR/S gene regulatory system is crucial for Methicillin-resistant Staphylococcus aureus (MRSA) virulence. Deleting saeR/S significantly reduces MRSA
Area of Science:
- Microbiology
- Infectious Diseases
- Immunology
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) poses significant threats in healthcare and community settings.
- Mechanisms of innate immune evasion by S. aureus are not fully understood.
- The saeR/S two-component gene regulatory system's role in S. aureus pathogenesis requires further investigation.
Purpose of the Study:
- To elucidate the role of the saeR/S gene regulatory system in S. aureus pathogenesis.
- To investigate the impact of saeR/S on MRSA virulence and immune evasion.
Main Methods:
- Created an isogenic deletion mutant of the saeR/S system in S. aureus strain MW2 (USA400).
- Evaluated virulence in mouse models of sepsis.
- Assessed bacterial survival and interaction with human neutrophils.
- Utilized microarray analysis to study gene expression changes.
Main Results:
- The saeR/S system is vital for the virulence of S. aureus MW2 in a mouse model of sepsis.
- Deletion of saeR/S significantly impaired S. aureus survival in human blood and resistance to neutrophil phagocytosis.
- Microarray analysis indicated that SaeR/S influences a broad range of genes involved in diverse biological functions.
Conclusions:
- The saeR/S gene regulatory system plays a critical role in S. aureus pathogenesis and virulence.
- SaeR/S is essential for MRSA's ability to evade innate immune responses, including neutrophil phagocytosis.
- These findings provide novel insights into S. aureus virulence regulation and its association with invasive disease.
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