Related Experiment Video
Updated: Mar 24, 2026

Quantifying the Cytotoxicity of Staphylococcus aureus Against Human Polymorphonuclear Leukocytes
Published on: January 3, 2020
Staphylococcus aureus α toxin potentiates opportunistic bacterial lung infections
Taylor S Cohen1, Jamese J Hilliard1, Omari Jones-Nelson1
1Department of Infectious Disease, MedImmune, Gaithersburg, MD 20878, USA.
Abstract:
Broad-spectrum antibiotic use may adversely affect a patient's beneficial microbiome and fuel cross-species spread of drug resistance. Although alternative pathogen-specific approaches are rationally justified, a major concern for this precision medicine strategy is that co-colonizing or co-infecting opportunistic bacteria may still cause serious disease. In a mixed-pathogen lung infection model, we find that the Staphylococcus aureus virulence factor α toxin potentiates Gram-negative bacterial proliferation, systemic spread, and lethality by preventing acidification of bacteria-containing macrophage phagosomes, thereby reducing effective killing of both S. aureus and Gram-negative bacteria. Prophylaxis or early treatment with a single α toxin neutralizing monoclonal antibody prevented proliferation of co-infecting Gram-negative pathogens and lethality while also promoting S. aureus clearance. These studies suggest that some pathogen-specific, antibody-based approaches may also work to reduce infection risk in patients colonized or co-infected with S. aureus and disparate drug-resistant Gram-negative bacterial opportunists.
Insights
Broad-spectrum antibiotics harm the microbiome. Targeting Staphylococcus aureus alpha toxin with antibodies can prevent deadly Gram-negative bacterial infections, offering a precision medicine approach.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Broad-spectrum antibiotics disrupt the microbiome and promote antibiotic resistance.
- Pathogen-specific treatments are promising but face challenges with polymicrobial infections.
Purpose of the Study:
- To investigate the role of Staphylococcus aureus alpha toxin in polymicrobial lung infections.
- To evaluate the efficacy of alpha toxin neutralization in a mixed-infection model.
Main Methods:
- Utilized a mixed-pathogen lung infection model involving Staphylococcus aureus and Gram-negative bacteria.
- Assessed the impact of alpha toxin on bacterial proliferation, host immune response, and lethality.
- Administered alpha toxin-neutralizing monoclonal antibodies for prophylaxis and early treatment.
Main Results:
- Staphylococcus aureus alpha toxin promotes Gram-negative bacterial growth and systemic spread by inhibiting macrophage phagosome acidification.
- Neutralization of alpha toxin reduced Gram-negative pathogen proliferation and lethality.
- Antibody treatment also enhanced Staphylococcus aureus clearance.
Conclusions:
- Staphylococcus aureus alpha toxin is a key factor in polymicrobial infections, exacerbating Gram-negative bacterial disease.
- Pathogen-specific antibody-based therapies targeting alpha toxin show potential for treating mixed infections, including those with drug-resistant Gram-negative bacteria.
Related Concept Videos
Staphylococcal Skin Infections
Bacterial Toxins
Atypical Pneumonia
Pneumonia II: Pathophysiology
Clinical Significance of Antibiotic Resistance
Mechanism of Antibiotic Resistance in MRSA

