Staphylococcal biofilms

Abstract

Staphylococcus epidermidis and Staphylococcus aureus are the most frequent causes of nosocomial infections and infections on indwelling medical devices, which characteristically involve biofilms. Recent advances in staphylococcal molecular biology have provided more detailed insight into the basis of biofilm formation in these opportunistic pathogens. A series of surface proteins mediate initial attachment to host matrix proteins, which is followed by the expression of a cationic glucosamine-based exopolysaccharide that aggregates the bacterial cells. In some cases, proteins may function as alternative aggregating substances. Furthermore, surfactant peptides have now been recognized as key factors involved in generating the three-dimensional structure of a staphylococcal biofilm by cell-cell disruptive forces, which eventually may lead to the detachment of entire cell clusters. Transcriptional profiling experiments have defined the specific physiology of staphylococcal biofilms and demonstrated that biofilm resistance to antimicrobials is due to gene-regulated processes. Finally, novel animal models of staphylococcal biofilm-associated infection have given us important information on which factors define biofilm formation in vivo. These recent advances constitute an important basis for the development of anti-staphylococcal drugs and vaccines.

Fig. 1

Phases of biofilm development in staphylococci. Biofilms form by initial attachment to a surface, which can occur on tissues or after covering of an abiotic surface by host matrix proteins in the human body (specific, protein-protein interaction), or directly to an abiotic surface (non-specific). Subsequently, biofilms grow and mature. The molecules that connect the cells in a staphylococcal biofilm are predominantly the exopolysaccharide PIA, teichoic acids, and some proteins such as the accumulation-associated protein Aap. Finally, cell clusters detach. Detachment is facilitated by expression of the surfactant-like PSM peptides, which are also important in producing the 3-dimensional structure of the biofilm. During infection, attachment is a crucial part of the colonization on host tissues or on indwelling medical devices, whereas detachment is a prerequisite for the dissemination of an infection.

Fig. 2

The biofilm exopolysaccharide PIA. A, PIA covers staphylococcal cells and sticks them together as the major component of the extracellular matrix (backscatter scanning electron microscopic picture of S. epidermidis). B, PIA is a homopolymer of beta 1-6–linked N-acetylglucosamine, of which about 10–20% of residues are de-acetylated. C, The biosynthesis of PIA in S. epidermidis occurs in 3 steps. (1) IcaA adds GlcNAc moieties from UDP-GlcNAc to the growing PIA chain. The IcaA transferase needs the presence of IcaD for full activity. (2) Presumably, the nascent PIA chain is then exported by IcaC. (3) After export, PIA is de-acetylated by the surface-attached IcaB to introduce positive charges, which are crucial for its surface location and biological function.

Fig. 3

Model of PSM function in biofilm structuring. (1) Cells actively expressing PSM beta peptides attach to a surface. (2) Later on, some cell clusters discontinue PSM beta expression for yet unknown reasons, possibly due to limited oxygen concentration. (3) Cell clusters with active PSM beta expression detach, leaving gaps in the biofilm, which ultimately leads to the typical structure of a biofilm with cell towers and fluid-filled channels.