Authors: T. S. Cohen, J. J. Hilliard, O. Jones-Nelson, A. E. Keller, T. ODay, C. Tkaczyk, A. DiGiandomenico, M. Hamilton, M. Pelletier, Q. Wang, B. A. Diep, V. T. M. Le, L. Cheng, J. Suzich, C. K. Stover, B. R. Sellman
Summary: 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.
Source:
Science Translational Medicine; 2016, 8 (329): 329ra31