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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

Analysis of the transcriptome of the spleen of mice infected with different S. epidermidis populations. BALB/c mice were challenged intravenously with 1 × 108 planktonic (P) (n = 2), biofilm (B) (n = 3), biofilm-released (BR) cells (n = 3), or sham-infected treated with PBS alone (PBS) (n = 2). Two hours post-infection, spleens were collected and microarray analysis was performed. (A) Principal component analysis; (B) Number of genes with increased and decreased transcription in each condition (P < 0.05, Empirical Bayes two-group test with Benjamini-Hochberg multiple testing correction). (C) Venn diagram showing the number of genes that are commonly (overlapping circles) and uniquely expressed (non-overlapping circles) in each condition; (D) Heatmap of the differentially expressed genes. White lines indicate non-detected genes or genes with no significant alterations (P > 0.05, Empirical Bayes two-group test with Benjamini-Hochberg multiple testing correction).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5037199&req=5

Figure 1: Analysis of the transcriptome of the spleen of mice infected with different S. epidermidis populations. BALB/c mice were challenged intravenously with 1 × 108 planktonic (P) (n = 2), biofilm (B) (n = 3), biofilm-released (BR) cells (n = 3), or sham-infected treated with PBS alone (PBS) (n = 2). Two hours post-infection, spleens were collected and microarray analysis was performed. (A) Principal component analysis; (B) Number of genes with increased and decreased transcription in each condition (P < 0.05, Empirical Bayes two-group test with Benjamini-Hochberg multiple testing correction). (C) Venn diagram showing the number of genes that are commonly (overlapping circles) and uniquely expressed (non-overlapping circles) in each condition; (D) Heatmap of the differentially expressed genes. White lines indicate non-detected genes or genes with no significant alterations (P > 0.05, Empirical Bayes two-group test with Benjamini-Hochberg multiple testing correction).

Mentions: The transcriptomic profile of mice infected with S. epidermidis planktonic, biofilm and biofilm-released cells was compared with that of non-infected mice in order to identify the genes expressed during infection induced by each of the three populations. Principal components analysis revealed that infected mice displayed a markedly different gene expression profile from non-infected controls (Figure 1A). The differences among infected mouse groups, however, were not that evident. The genes with the highest or lowest levels of transcription were similar in the three groups of infected mice (Tables 1, 2). Nevertheless, despite these general similarities important differences were found in the number of genes with increased and decreased transcription (Figure 1B). Within the 243 genes found differentially expressed (P < 0.05) in mice infected with biofilm-released cells, 121 were exclusive to this infecting phenotype (Figure 1C), where 96 had increased transcription (above 1.5-fold change) and 25 had decreased transcription (above −1.5-fold change; Figure 1D). Among the genes with increased transcription in splenocytes of mice infected with biofilm-released cells, we found significant enrichment of several GO clusters (Table 3) including positive regulation of leukocyte cell-cell adhesion, tumor necrosis factor-mediated signaling and T cell activation, and negative regulation of mitogen activated protein kinases (MAPK) cascade and interleukin-10 production. Interestingly, GO terms associated with programmed cell death such as regulation of intrinsic apoptotic signaling pathways, development of cell death, and cell killing were also enriched. Finally, we observed that the great majority of the transcripts of the genes with increased expression in mice infected with biofilm-released cells were those encoding proteins mostly localized to the cytoplasm or in cells' organelles (Table 3). No enrichment was found among down-regulated genes, in any of the conditions tested. For further information regarding the GO terms found enriched in mice infected with planktonic or biofilm cells please see Supplementary Material.


Staphylococcus epidermidis Biofilm-Released Cells Induce a Prompt and More Marked In vivo Inflammatory-Type Response than Planktonic or Biofilm Cells
Analysis of the transcriptome of the spleen of mice infected with different S. epidermidis populations. BALB/c mice were challenged intravenously with 1 × 108 planktonic (P) (n = 2), biofilm (B) (n = 3), biofilm-released (BR) cells (n = 3), or sham-infected treated with PBS alone (PBS) (n = 2). Two hours post-infection, spleens were collected and microarray analysis was performed. (A) Principal component analysis; (B) Number of genes with increased and decreased transcription in each condition (P < 0.05, Empirical Bayes two-group test with Benjamini-Hochberg multiple testing correction). (C) Venn diagram showing the number of genes that are commonly (overlapping circles) and uniquely expressed (non-overlapping circles) in each condition; (D) Heatmap of the differentially expressed genes. White lines indicate non-detected genes or genes with no significant alterations (P > 0.05, Empirical Bayes two-group test with Benjamini-Hochberg multiple testing correction).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037199&req=5

Figure 1: Analysis of the transcriptome of the spleen of mice infected with different S. epidermidis populations. BALB/c mice were challenged intravenously with 1 × 108 planktonic (P) (n = 2), biofilm (B) (n = 3), biofilm-released (BR) cells (n = 3), or sham-infected treated with PBS alone (PBS) (n = 2). Two hours post-infection, spleens were collected and microarray analysis was performed. (A) Principal component analysis; (B) Number of genes with increased and decreased transcription in each condition (P < 0.05, Empirical Bayes two-group test with Benjamini-Hochberg multiple testing correction). (C) Venn diagram showing the number of genes that are commonly (overlapping circles) and uniquely expressed (non-overlapping circles) in each condition; (D) Heatmap of the differentially expressed genes. White lines indicate non-detected genes or genes with no significant alterations (P > 0.05, Empirical Bayes two-group test with Benjamini-Hochberg multiple testing correction).
Mentions: The transcriptomic profile of mice infected with S. epidermidis planktonic, biofilm and biofilm-released cells was compared with that of non-infected mice in order to identify the genes expressed during infection induced by each of the three populations. Principal components analysis revealed that infected mice displayed a markedly different gene expression profile from non-infected controls (Figure 1A). The differences among infected mouse groups, however, were not that evident. The genes with the highest or lowest levels of transcription were similar in the three groups of infected mice (Tables 1, 2). Nevertheless, despite these general similarities important differences were found in the number of genes with increased and decreased transcription (Figure 1B). Within the 243 genes found differentially expressed (P < 0.05) in mice infected with biofilm-released cells, 121 were exclusive to this infecting phenotype (Figure 1C), where 96 had increased transcription (above 1.5-fold change) and 25 had decreased transcription (above −1.5-fold change; Figure 1D). Among the genes with increased transcription in splenocytes of mice infected with biofilm-released cells, we found significant enrichment of several GO clusters (Table 3) including positive regulation of leukocyte cell-cell adhesion, tumor necrosis factor-mediated signaling and T cell activation, and negative regulation of mitogen activated protein kinases (MAPK) cascade and interleukin-10 production. Interestingly, GO terms associated with programmed cell death such as regulation of intrinsic apoptotic signaling pathways, development of cell death, and cell killing were also enriched. Finally, we observed that the great majority of the transcripts of the genes with increased expression in mice infected with biofilm-released cells were those encoding proteins mostly localized to the cytoplasm or in cells' organelles (Table 3). No enrichment was found among down-regulated genes, in any of the conditions tested. For further information regarding the GO terms found enriched in mice infected with planktonic or biofilm cells please see Supplementary Material.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus