Staphylococcus epidermidis Biofilm-Released Cells Induce a Prompt and More Marked In vivo Inflammatory-Type Response than Planktonic or Biofilm Cells.

Angela França,Manuel Vilanova,Alexandra Correia,Nuno Cerca,Gerald B Pier,Begoña Pérez-Cabezas

doi:10.3389/fmicb.2016.01530

Abstract

Staphylococcus epidermidis biofilm formation on indwelling medical devices is frequently associated with the development of chronic infections. Nevertheless, it has been suggested that cells released from these biofilms may induce severe acute infections with bacteraemia as one of its major associated clinical manifestations. However, how biofilm-released cells interact with the host remains unclear. Here, using a murine model of hematogenously disseminated infection, we characterized the interaction of cells released from S. epidermidis biofilms with the immune system. Gene expression analysis of mouse splenocytes suggested that biofilm-released cells might be particularly effective at activating inflammatory and antigen presenting cells and inducing cellular apoptosis. Furthermore, biofilm-released cells induced a higher production of pro-inflammatory cytokines, in contrast to mice infected with planktonic cells, even though these had a similar bacterial load in livers and spleens. Overall, these results not only provide insights into the understanding of the role of biofilm-released cells in S. epidermidis biofilm-related infections and pathogenesis, but may also help explain the relapsing character of these infections.

Highlights

Staphylococcus epidermidis is one of the most important etiological agents of device-associated infections due to its ability to adhere and form biofilms on the surface of indwelling medical devices (Vuong and Otto, 2002; Otto, 2009)
Among the genes with increased transcription in splenocytes of mice infected with biofilm-released cells, we found significant enrichment of several Gene ontology (GO) clusters (Table 3) including positive regulation of leukocyte cell-cell adhesion, tumor necrosis factormediated signaling and T cell activation, and negative regulation of mitogen activated protein kinases (MAPK) cascade and interleukin-10 production
We have recently shown that biofilmreleased cells, obtained using the same experimental model used are more tolerant than planktonic cells, or even biofilm cells, to antibiotics commonly used for staphylococcal infections treatment (Franca et al, 2016)

Summary

Introduction

Staphylococcus epidermidis is one of the most important etiological agents of device-associated infections due to its ability to adhere and form biofilms on the surface of indwelling medical devices (Vuong and Otto, 2002; Otto, 2009). In the case of S. epidermidis, it is only known that biofilm-released cells present higher tolerance than planktonic and biofilm cells to antibiotics (Franca et al, 2016). Our results showed that S. epidermidis biofilm-released cells induce a prompt and more marked inflammatory-type response than do their planktonic or biofilm counterparts. These findings showed that particular properties of the biofilm-released cells need to be taken into account to efficiently target and treat acute infections originating from S. epidermidis biofilms

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