Abstract

The matrix proteins of Staphylococcus aureus biofilm have not been well defined. Previous efforts to identify these proteins were performed using in vitro systems. Here we use a proteomic approach to identify biofilm matrix proteins directly from infected bone implants using a rat model of orthopedic implant-associated S. aureus infection. Despite heavy presence of host proteins, a total of 28 and 105 S. aureus proteins were identified during acute infection and chronic infection, respectively. Our results show that biofilm matrix contains mostly intracellular cytoplasmic proteins and, to a much less extent, extracellular and cell surface-associated proteins. Significantly, leukocidins were identified in the biofilm matrix during chronic infection, suggesting S. aureus is actively attacking the host immune system even though they are protected within the biofilm. The presence of two surface-associated proteins, Ebh and SasF, in the infected bone tissue during acute infection was confirmed by immunohistochemistry. In addition, a large number of host proteins were found differentially expressed in response to S. aureus biofilm formed on bone implants.

Highlights

  • Staphylococcus aureus can cause a range of infections

  • The composition of matrix protein of biofilms formed during an S. aureus infection has not been reported

  • We were able to obtain enough biofilm materials for bacterial protein identification from implants harvested during acute infection as well as chronic infection

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Summary

Introduction

Treatment for S. aureus infections is largely limited to conventional antibiotic therapy but failures are common due to emergence of antibiotic resistance strains as well as intrinsic antibiotic resistance attributed to biofilm formation. Biofilm is composed of multiple layers of bacteria encased and interconnected in an extracellular matrix that forms a complex three-dimensional structure, which provides protection against host defenses and limits the therapeutic efficacy of all currently available antibiotics [1, 2]. Many S. aureus strains have been shown to form a PIA-independent biofilm composed of proteins and/or bacterial extracellular DNA (eDNA) [5,6,7]. These studies indicate that S. aureus biofilm matrix contains a large

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