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Updated: Dec 9, 2025

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Silence as a way of niche adaptation: mecC-MRSA with variations in the accessory gene regulator (agr) functionality
Charlotte Huber1, Ivonne Stamm2, Wilma Ziebuhr3
1Advanced Light and Electron Microscopy (ZBS4), Robert Koch Institute, Berlin, Germany.
Abstract:
Functionality of the accessory gene regulator (agr) quorum sensing system is an important factor promoting either acute or chronic infections by the notorious opportunistic human and veterinary pathogen Staphylococcus aureus. Spontaneous alterations of the agr system are known to frequently occur in human healthcare-associated S. aureus lineages. However, data on agr integrity and function are sparse regarding other major clonal lineages. Here we report on the agr system functionality and activity level in mecC-carrying methicillin resistant S. aureus (MRSA) of various animal origins (n = 33) obtained in Europe as well as in closely related human isolates (n = 12). Whole genome analysis assigned all isolates to four clonal complexes (CC) with distinct agr types (CC599 agr I, CC49 agr II, CC130 agr III and CC1943 agr IV). Agr functionality was assessed by a combination of phenotypic assays and proteome analysis. In each CC, isolates with varying agr activity levels were detected, including the presence of completely non-functional variants. Genomic comparison of the agr I-IV encoding regions associated these phenotypic differences with variations in the agrA and agrC genes. The genomic changes were detected independently in divergent lineages, suggesting that agr variation might foster viability and adaptation of emerging MRSA lineages to distinct ecological niches.
Insights
The accessory gene regulator (agr) quorum sensing system in Staphylococcus aureus shows varied functionality, including non-functional variants, across different clonal lineages. Genomic variations in agrA and agrC genes likely drive these adaptations in methicillin-resistant S. aureus (MRSA).
Area of Science:
- Microbiology
- Genomics
- Pathogen Adaptation
Background:
- The accessory gene regulator (agr) quorum sensing system is crucial for Staphylococcus aureus virulence, influencing acute and chronic infections.
- Spontaneous agr system alterations are common in human healthcare-associated S. aureus, but data on other lineages are limited.
Purpose of the Study:
- To investigate agr system functionality and activity in mecC-carrying methicillin-resistant S. aureus (MRSA) from animal and human origins.
- To correlate genomic variations with observed phenotypic differences in agr activity.
Main Methods:
- Whole genome analysis to assign isolates to clonal complexes (CC) and agr types.
- Phenotypic assays and proteome analysis to assess agr functionality and activity levels.
- Genomic comparison of agr encoding regions (agrA, agrC) to identify variations.
Main Results:
- Isolates were assigned to four distinct clonal complexes (CC599, CC49, CC130, CC1943) with different agr types.
- Varied levels of agr activity, including completely non-functional variants, were detected within each CC.
- Genomic variations in agrA and agrC genes were associated with observed differences in agr functionality.
Conclusions:
- Agr system variation is prevalent across different S. aureus clonal lineages, including MRSA.
- Genomic changes in agrA and agrC appear to be key drivers of altered agr functionality.
- Agr variation may facilitate the adaptation and viability of emerging MRSA lineages in diverse ecological niches.
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