Related Experiment Video
Updated: Jul 12, 2025
Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Differential survival of Staphylococcal species in macrophages
Janina Bayer1,2, Janna Becker1,2, Xiao Liu2,3
1Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
Abstract:
Staphylococcus aureus is considered an extracellular pathogen, yet the bacterium is able to survive within and escape from host cells. An agr/sae mutant of strain USA300 is unable to escape from macrophages but can replicate and survive within. We questioned whether such "non-toxic" S. aureus resembles the less pathogenic coagulase-negative Staphylococcal (CoNS) species like S. epidermidis, S. carnosus, S. lugdunensis, S. capitis, S. warneri, or S. pettenkoferi. We show that the CoNS are more efficiently killed in macrophage-like THP-1 cells or in human primary macrophages. Mutations in katA, copL, the regulatory system graRS, or sigB did not impact bacterial survival in THP-1 cells. Deletion of the superoxide dismutases impaired S. aureus survival in primary macrophages but not in THP-1 cells. However, expression of the S. aureus-specific sodM in S. epidermidis was not sufficient to protect this species from being killed. Thus, at least in those cells, better bacterial survival of S. aureus could not be linked to higher protection from ROS. However, "non-toxic" S. aureus was found to be insensitive to pH, whereas most CoNS were protected when phagosomal acidification was inhibited. Thus, species differences are at least partially linked to differences in sensitivity to acidification.
Insights
Staphylococcus aureus survives better than coagulase-negative staphylococci (CoNS) in macrophages. Differences in pH sensitivity, not reactive oxygen species, explain this enhanced survival.
Area of Science:
- Microbiology
- Immunology
- Pathogen Survival
Background:
- Staphylococcus aureus is an extracellular pathogen capable of intracellular survival and escape.
- The agr/sae mutant of S. aureus USA300 survives within macrophages but cannot escape.
- The intracellular survival mechanisms of S. aureus and its comparison to less pathogenic coagulase-negative staphylococci (CoNS) remain unclear.
Purpose of the Study:
- To investigate the intracellular survival mechanisms of Staphylococcus aureus compared to CoNS species.
- To determine if S. aureus's enhanced intracellular survival is linked to resistance against reactive oxygen species (ROS) or pH.
- To elucidate species-specific differences in bacterial survival within macrophages.
Main Methods:
- Comparison of S. aureus and CoNS survival in THP-1 cells and human primary macrophages.
- Assessment of the impact of mutations in katA, copL, graRS, sigB, and superoxide dismutases on S. aureus survival.
- Evaluation of S. aureus-specific sodM expression in S. epidermidis.
- Analysis of bacterial sensitivity to phagosomal acidification.
Main Results:
- CoNS species were killed more efficiently by macrophages than S. aureus.
- Mutations in katA, copL, graRS, or sigB did not affect S. aureus survival in THP-1 cells.
- Superoxide dismutase deletion impaired S. aureus survival in primary macrophages but not THP-1 cells.
- S. aureus exhibited insensitivity to pH, while CoNS were protected by inhibited phagosomal acidification.
Conclusions:
- S. aureus's superior survival in macrophages is not solely attributed to ROS resistance.
- Differences in pH sensitivity, particularly to phagosomal acidification, contribute significantly to species-specific survival outcomes.
- Understanding these mechanisms is crucial for developing targeted therapeutic strategies against S. aureus infections.
