The bacterial envelope as a target for novel anti-MRSA antibiotics

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate S. aureus (VISA) are spreading worldwide, making the search for antibiotics directed against new targets a high priority. Drugs that anchor in the bacterial membrane (e.g. ceragenins and lipopeptides) or that target the bacterial membrane and proteic (lipoglycopeptides) or lipidic (glycodepsipeptides) cell wall precursors seem to have the most potential because they show a fast and extensive bactericidal effect and are probably less prone to select for resistance owing to the difficulty in modifying their targets in a way that is compatible with bacterial survival. The efficacy of lipopeptides and lipoglycopeptides has been demonstrated in the treatment of skin and skin structure infections, and bacteremia caused by resistant S. aureus. Ceragenins and glycodepsipeptides are restricted to topical applications because of their unsatisfactory safety profile. The mode of action, pharmacological and microbiological properties and target indications of these anti-MRSA agents, which function by disturbing membrane integrity, are reviewed in this article.