Prevention and treatment of Staphylococcus aureus biofilms

Abstract

S. aureus colonizes both artificial and tissue surfaces in humans causing chronic persistent infections that are difficult to cure. It is a notorious pathogen due to its antibiotic recalcitrance and phenotypic adaptability, both of which are facilitated by its ability to develop biofilms. S. aureus biofilms challenge conventional anti-infective approaches, most notably antibiotic therapy. Therefore there is an unmet need to develop and include parallel approaches that target S. aureus biofilm infections. This review discusses two broad anti-infective strategies: (1) preventative approaches (anti-biofilm surface coatings, the inclusion of biofilm-specific vaccine antigens); and (2) approaches aimed at eradicating established S. aureus biofilms, particularly those associated with implant infections. Advances in understanding the distinct nature of S. aureus biofilm development and pathogenesis have led to growing optimism in S. aureus biofilm targeted anti-infective strategies. Further research is needed however, to see the successful administration and validation of these approaches to the diverse types of infections caused by S. aureus biofilms from multiple clinical strains.

Keywords: Staphylococcus aureus; anti-infective strategies; antibiotic tolerance; biofilm infections; device related infections; persistence; prosthetic implants.

Figure 1. Strategies for prevention and treatment of S. aureus biofilms

A summary of the life cycle of a S. aureus biofilm, depicting the various stages of attachment, subsequent development, dispersal and colonization of new sites, is shown. Each of these stages represents possibilities for therapeutic disruptive intervention strategies. Broadly these strategies break down into (1) disruption at the surface (inner part of ring) through physical surface modification or surface-mediated delivery of antimicrobial/antibiofilm agents or (2) systemic or local delivery from the surrounding tissue or body fluids (outer part of the ring). Biofilm single cells and clusters are attached to a representative surface depicted by the blue ring. Since established biofilms can exhibit all stages of the growth cycle simultaneously due to highly localized structural heterogeneity, it is likely that for many patients multiple antibiofilm strategies will be required for effective prevention or treatment of the infection. EPS: Extracellular polymeric substances; PSM: Phenol soluble modulin; QS: Quorum sensing.