Widespread methicillin-resistant Staphylococcus aureus (S. aureus) infections within community and healthcare settings are responsible for accelerated development of antibiotic resistance. As the antibiotic pipeline began drying up, alternative strategies were sought for future treatment of S. aureus infections. Here, we review immune-based anti-staphylococcal strategies that, unlike conventional antibiotics, target non-essential gene products elaborated by the pathogen. These strategies stimulate narrow or broad host immune mechanisms that are critical for anti-staphylococcal defenses. Alternative approaches aim to disrupt bacterial virulence mechanisms that enhance pathogen survival or induce immunopathology. Although immune-based therapeutics are unlikely to replace antibiotics in patient treatment in the near term, they have the potential to significantly improve upon the performance of antibiotics for treatment of invasive staphylococcal diseases.
Keywords: CCAAT/enhancer binding protein (C/EBPε); Hypoxia-inducible factor (HIF)-1α; chronic granulomatous disease (CGD); cyclic-di–guanosine monophosphate (c-di-GMP); immune boosting strategy; innate defense regulator peptide (IDR-1); mesenchymal stem cells (MSC); methicillin-resistant S. aureus (MRSA); neutrophil extracellular traps (NETs); serum therapy.