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Updated: May 2, 2026
Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Bacteriophage-aided intracellular killing of engulfed methicillin-resistant Staphylococcus aureus (MRSA) by murine
Sandeep Kaur1, Kusum Harjai, Sanjay Chhibber
1Department of Microbiology, Panjab University, Chandigarh, 160014, India.
Abstract:
Phages are known to effectively kill extracellularly multiplying bacteria as they do not have the ability of intracellular penetration within the animal cells. However, the present manuscript focuses on studying the impact of surface-adsorbed phage particles on the killing of engulfed Staphylococcus aureus inside phagocytic cells. Mouse peritoneal macrophages were isolated and cultured, followed by evaluation of their ability of bacterial uptake and killing. The intracellular killing potential of macrophages in the presence of unadsorbed free phage as well as phage adsorbed onto S. aureus 43300 was studied. Phage added alone to macrophage preparation did not influence intracellular killing of engulfed S. aureus by macrophages. However, phage adsorbed onto host bacterial cells (utilizing host bacteria as a vehicle to carry the lytic phage into the phagocytic compartment) brought about time-dependent and titre-dependent significant reduction in the number of viable intracellular cocci. Phage particles that shuttled inside the macrophage along with bacteria also significantly reduced cytotoxic damage caused by methicillin-resistant S. aureus (MRSA). This in turn enhanced the bactericidal killing potential of phagocytic cells. In earlier studies the inability of phages to kill intracellular bacteria has been thought to be a major drawback of phage therapy. For the first time results of this study confirm the killing ability of the broad host range lytic phage MR-5 of both extracellular as well as intracellular engulfed S. aureus inside macrophages. This approach shall not only restrict intracellular proliferation of staphylococci within the myeloid cells but also protect the host from further relapse of infection and treatment failures.
Insights
This study shows that phages adsorbed onto Staphylococcus aureus can kill bacteria within macrophages, overcoming a key limitation of phage therapy. This approach enhances the immune cells
Area of Science:
- Bacteriology
- Immunology
- Microbial Therapeutics
Background:
- Bacteriophages (phages) are viruses that infect bacteria and are primarily known for killing extracellular bacteria.
- Phages' inability to penetrate host animal cells has limited their efficacy against intracellular bacterial infections.
- Staphylococcus aureus, including methicillin-resistant strains (MRSA), can survive and proliferate within phagocytic cells, complicating treatment.
Purpose of the Study:
- To investigate the impact of surface-adsorbed phage particles on the intracellular killing of Staphylococcus aureus by macrophages.
- To determine if using bacteria as a vehicle can deliver lytic phages into phagocytic cells for enhanced bacterial clearance.
- To assess the potential of this strategy to overcome phage therapy's limitations against intracellular pathogens.
Main Methods:
- Isolation and culture of mouse peritoneal macrophages.
- Evaluation of macrophage bacterial uptake and intracellular killing capabilities.
- Testing the efficacy of free phages versus phages adsorbed onto S. aureus for intracellular bacterial killing.
Main Results:
- Free phages did not significantly affect intracellular S. aureus killing by macrophages.
- Phages adsorbed onto S. aureus significantly reduced viable intracellular bacteria in a time- and titre-dependent manner.
- Phage-bacteria complexes delivered into macrophages reduced cytotoxic damage and enhanced the cells' bactericidal potential.
Conclusions:
- For the first time, this study demonstrates the ability of a broad-host-range lytic phage (MR-5) to kill both extracellular and intracellular S. aureus within macrophages.
- Utilizing host bacteria as a vehicle to carry phages into phagocytic cells is an effective strategy to combat intracellular staphylococcal infections.
- This approach holds promise for restricting intracellular bacterial proliferation, preventing infection relapse, and improving outcomes in phage therapy.
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