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Updated: Oct 20, 2025

Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Commensal bacteria augment Staphylococcus aureus infection by inactivation of phagocyte-derived reactive oxygen
Josie F Gibson1,2,3, Grace R Pidwill1,2, Oliver T Carnell1,2
1Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, United Kingdom.
Abstract:
Staphylococcus aureus is a human commensal organism and opportunist pathogen, causing potentially fatal disease. The presence of non-pathogenic microflora or their components, at the point of infection, dramatically increases S. aureus pathogenicity, a process termed augmentation. Augmentation is associated with macrophage interaction but by a hitherto unknown mechanism. Here, we demonstrate a breadth of cross-kingdom microorganisms can augment S. aureus disease and that pathogenesis of Enterococcus faecalis can also be augmented. Co-administration of augmenting material also forms an efficacious vaccine model for S. aureus. In vitro, augmenting material protects S. aureus directly from reactive oxygen species (ROS), which correlates with in vivo studies where augmentation restores full virulence to the ROS-susceptible, attenuated mutant katA ahpC. At the cellular level, augmentation increases bacterial survival within macrophages via amelioration of ROS, leading to proliferation and escape. We have defined the molecular basis for augmentation that represents an important aspect of the initiation of infection.
Insights
Microorganisms can enhance Staphylococcus aureus (S. aureus) infections through a process called augmentation. This study reveals augmentation protects bacteria from immune defenses, aiding infection initiation.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Staphylococcus aureus is a significant human pathogen.
- Its pathogenicity can be increased by co-infecting microorganisms (augmentation).
- The mechanism of augmentation, particularly macrophage interaction, remains unclear.
Purpose of the Study:
- To investigate the breadth of microorganisms capable of augmenting S. aureus.
- To elucidate the mechanism by which augmentation enhances S. aureus pathogenicity.
- To explore the potential of augmentation as a vaccine model.
Main Methods:
- Testing various cross-kingdom microorganisms for augmentation of S. aureus.
- In vitro assessment of bacterial survival against reactive oxygen species (ROS).
- In vivo studies using ROS-susceptible S. aureus mutants (katA ahpC).
- Cellular studies examining bacterial survival within macrophages.
Main Results:
- Diverse microorganisms, including Enterococcus faecalis, can augment S. aureus virulence.
- Augmentation protects S. aureus from ROS in vitro.
- Augmentation restores virulence to ROS-susceptible mutants in vivo.
- Augmentation enhances bacterial survival within macrophages by mitigating ROS, promoting proliferation and escape.
Conclusions:
- Augmentation is a conserved phenomenon mediated by cross-kingdom microbial interactions.
- The mechanism involves protecting bacteria from host ROS, facilitating intracellular survival and proliferation.
- Augmentation represents a critical factor in initiating infection and offers a novel vaccine strategy.
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