An antidote for Staphylococcus aureus pneumonia?

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of bacterial infections in the United States. Severe invasive MRSA infections, which include pneumonia, are difficult to treat because the bacteria are resistant to antibiotics. A new report now shows that immunization against alpha-hemolysin (Hla), a cytolytic toxin secreted by most S. aureus strains, protects mice against lethal pneumonia. This finding represents the first successful vaccine strategy for the treatment of staphylococcal pneumonia.

Figure 1.

Potential pitfall of S. aureus vaccines designed to enhance bacterial uptake by neutrophils. S. aureus is opsonized by bacteria-specific antibody and serum complement, which promote rapid binding and uptake of the bacteria by neutrophils. After uptake, S. aureus uses multiple mechanisms to survive and cause the death of the cell, allowing the escape of sequestered bacteria

Figure 2.

Hla-induced pneumonia and mechanism of protection by Hla antibodies. (A) Hla may cause direct destruction of lung epithelial cells and/or elicit an inflammatory response, including production of proinflammatory cytokines such as interleukin 1b, which contributes to pneumonia. (B) Anti-Hla antibody blocks Hla, thus inhibiting its cytotoxic effects.