Structural basis of Staphylococcus epidermidis biofilm formation: mechanisms and molecular interactions

Abstract

Staphylococcus epidermidis is a usually harmless commensal bacterium highly abundant on the human skin. Under defined predisposing conditions, most importantly implantation of a medical device, S. epidermidis, however, can switch from a colonizing to an invasive life style. The emergence of S. epidermidis as an opportunistic pathogen is closely linked to the biofilm forming capability of the species. During the past decades, tremendous advance regarding our understanding of molecular mechanisms contributing to surface colonization has been made, and detailed information is available for several factors active during the primary attachment, accumulative or dispersal phase of biofilm formation. A picture evolved in which distinct factors, though appearing to be redundantly organized, take over specific and exclusive functions during biofilm development. In this review, these mechanisms are described in molecular detail, with a highlight on recent insights into multi-functional S. epidermidis cell surface proteins contributing to surface adherence and intercellular adhesion. The integration of distinct biofilm-promoting factors into regulatory networks is summarized, with an emphasis on mechanism that could allow S. epidermidis to flexibly adapt to changing environmental conditions present during colonizing or invasive life-styles.

Keywords: Aap; AtlE; Embp; PIA; Staphylococcus epidermidis biofilm formation; biofilm accumulation; primary attachment; regulation.

Figure 1

Schematic representation of Embp and relative position of recombinant proteins for which functional data are available. Embp possesses an N-terminal YSIRK motif containing export signal, which is followed by a region of unordered conformation. The central part is comprised of the FIVAR or FIVAR-GA repeats, while the C-terminal end comprises up by four Domains of Unknown Function (DUF) and a putative transmembrane (TM) region (Christner et al., 2010). Embp32 is a recombinant Embp fragment (aa 9180–9421) from S. epidermidis NCTC11047 spanning four alternating FIVAR and FIVAR-GA repeats and that exhibits fibronectin binding capacity (Williams et al., 2002). rEmbp2588 (aa 2588–3187) contains seven FIVAR-only repeat units, while rEmbp6599 (aa 6599–7340) consists of six G-related albumin binding (GA) modules intercalated by FIVAR repeats. The rEmbp2588 and rEmbp6599 both bind to surface immobilized fibronectin (Christner et al., 2010).

Figure 2

Schematic representation of SarA effects on expression of independent intercellular adhesins. While in trypticase soy broth, sarA is expressed, leading to icaADBC expression and PIA dependent biofilm formation, down-regulation of sarA leads to an de-repression of embp expression, allowing for maintenance of a biofilm-positive phenotype despite icaADBC down-regulation and loss of PIA production. Parallel to embp, following inactivation of sarA, metalloprotease sepA is up-regulated, leading to increased AtlE processing, autolysis and subsequent eDNA release. Potentially, the over-production of SepA also contributes to Aap-dependent biofilm accumulation by proteolytically processing of the mature protein, resulting in the removal of it's A domain. Environmental (potentially also host) factors that repress sarA expression are unknown, as are the pathways via which sarA itself is regulated.