Mechanisms of staphylococcus epidermidis biofilm formation in different types of biomaterial-related infections

D. Mack, L. G. Harris, R. Jeeves, B. Pascoe, A. P. Davis, T. S. Wilkinson

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Staphylococcus epider-midis is the prototype organism involved in medical biofilm disease resulting in infected implants like intravascular catheters or joint prostheses yearly affecting millions of patients worldwide. These infections persist despite antimicrobial treatment due to organization of S. epidermidis in surface adherent biofilms fre-quently requiring device removal. Biofilms are formed in two phases: initial attachment of bacteria is followed by accumulation of bacte-ria in multiple layers. Attachment is a multi-factorial process involving a variety of specific protein and polysaccharide factors depending on surface properties. Results & DISCUSSION: We identified polysaccharide intercellular adhesin (PIA) as the central functional factor in biofilm accu-mulation. PIA is a homoglycan of β-1,6-linked N-acetylglucosamine residues of which 15-20% are deacetylated. PIA is synthesised by the gene products of the icaADBC locus. Epidemiologi-cal studies defined PIA as the main functional molecule involved in biofilm accumulation in S. epidermidis. Using isogenic biofilm-negative icaA-insertion mutants expression of PIA and biofilm formation were defined as essential virulence factors of S. epidermidis in foreign body infection models [1]. Interestingly, expression of PIA as a mecha-nism for biofilm accumulation is not unique to S. epidermidis. Numerous other staphylococcal species including Staphylococcus aureus, S. caprae, S. lugdunensis, and other coagulase-negative staphylococci possess the icaADBC locus and may synthesise PIA. Additionally, a number of Gram-negative human pathogens including Escherichia coli, Aggregatibacter actinomycetemcomitans, Actinobacillus pleuro-pneumoniae, Yersinia pestis, Acinetobacter baumannii, and Bordetella spp. synthesise PIA using enzymes encoded by orthologous gene loci referred to as pgaABCD or hmsHFRS, in-dicating that PIA is a general principle in biofilm formation in many eubacteria [1]. Study of the molecular epidemiology of S. epi-dermidis strains revealed that almost all isolates from port-catheter infections were icaADBC-positive and proficient for PIA-synthesis while the strains from prosthetic joint infections pro-duced biofilms frequently in an icaADBC- and PIA-independent manner [2]. Consequently we discovered two additional mechanism of biofilm accumulation, which were completely polysaccharide-independent. The highly prevalent accumulation associated protein (Aap) is activated by proteolytic processing by staphylococcal or host proteases generating an intercellular adhesin mediating biofilm accu-mulation [3]. Apparently, S. epidermidis can use factors of innate immunity to generate phagocytosis resistant bacterial aggregates and biofilm leading to immune escape and per-sistence. The giant 1 MDa extracellular matrix binding protein Embp acts as an intercellular adhesin in some S. epidermidis strains inde-pendent of PIA and Aap [4]. The accessory gene regulator agr is the major quorum sensing system in staphylococci, which uses four different octapeptides, defining agr-groups, as quorum signals. RNAIII transcript is the major effector of agr-activation in the late exponential growth phase, which also encodes δ-toxin, a proinflammatory factor belonging to the phenol-soluble modulins produced by staphylococci. In chronic device related infec-tion S. epidermidis strains of agr-group 1 are overrepresented compared to controls. Addi-tionally, strains emerge during chronic infec-tion, which no longer express δ-toxin investi-gated as a surrogate of agr-activation. Tran-scriptional analysis revealed that there is no correlation between δ-toxin expression and RNAIII upregulation indicating presence of post-transcriptional regulators controlling δ-toxin expression [5].
Original languageEnglish
Pages (from-to)21
Number of pages1
JournalEuropean Cells and Materials
Volume21
Issue number2
Publication statusPublished - 1 Jul 2011

Keywords

  • biomaterial
  • toxin
  • polysaccharide
  • adhesin
  • protein
  • virulence factor
  • n acetylglucosamine
  • phenol
  • enzyme
  • binding protein
  • proteinase
  • infection
  • biofilm
  • Staphylococcus epidermidis
  • implant
  • Staphylococcus
  • joint prosthesis
  • bacterium
  • human
  • model
  • patient
  • gene product
  • gene locus
  • Bordetella
  • molecular epidemiology
  • mutant
  • catheter infection
  • foreign body
  • synthesis
  • species
  • intravascular catheter
  • Acinetobacter baumannii
  • Yersinia pestis
  • Actinobacillus
  • Aggregatibacter actinomycetemcomitans
  • upregulation
  • surface property
  • Escherichia coli
  • growth curve
  • pathogenesis
  • coagulase negative Staphylococcus
  • infectious arthritis
  • device removal
  • phagocytosis
  • innate immunity
  • Staphylococcus aureus
  • extracellular matrix
  • processing
  • gene
  • quorum sensing
  • growth
  • antimicrobial therapy
  • devices
  • organisms

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