Staphylococcus aureus biofilms: recent developments in biofilm dispersal

Abstract

Staphylococcus aureus is a major cause of nosocomial and community-acquired infections and represents a significant burden on the healthcare system. S. aureus attachment to medical implants and host tissue, and the establishment of a mature biofilm, play an important role in the persistence of chronic infections. The formation of a biofilm, and encasement of cells in a polymer-based matrix, decreases the susceptibility to antimicrobials and immune defenses, making these infections difficult to eradicate. During infection, dispersal of cells from the biofilm can result in spread to secondary sites and worsening of the infection. In this review, we discuss the current understanding of the pathways behind biofilm dispersal in S. aureus, with a focus on enzymatic and newly described broad-spectrum dispersal mechanisms. Additionally, we explore potential applications of dispersal in the treatment of biofilm-mediated infections.

Keywords: Staphylococcus aureus; biofilm; dispersal; nuclease; protease; stringent response.

Figure 1

(A) Model of S. aureus biofilm growth cycle. In summary, upon coming into contact with a surface, planktonic cells attach through surface-associated proteins. Following attachment, cells divide and begin production of the extracellular matrix, which leads to the formation of a microcolony. As cell division continues, biomass accumulates and a mature biofilm is formed. Environmental signals within the biofilm trigger the activation of dispersal mechanisms, and upon dispersal, cells re-enter a planktonic growth state and can seed new sites for biofilm formation. (B) Treatment of a S. aureus biofilm. Antibiotic exposure will kill susceptible planktonic cells and metabolically active cells near the surface of the biofilm. However, persister cells and metabolically dormant cells within the biofilm survive and remain protected from immune defenses by the biofilm matrix. Treatment with dispersal agents increases the effectiveness of antibiotic penetration and promotes clearance. Antibiotic sensitive cells within the biofilm are exposed and killed after degradation of the matrix, and the antibiotic tolerant cells (such as persisters) survive and are susceptible to the immune system.