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Volume 153, Issue 12

The group B streptococcal alpha C protein binds -integrin through a novel KTD motif that promotes internalization of GBS within human epithelial cells Free

Abstract

Group B (GBS) is the leading cause of bacterial pneumonia, sepsis and meningitis among neonates and a cause of morbidity among pregnant women and immunocompromised adults. GBS epithelial cell invasion is associated with expression of alpha C protein (ACP). Loss of ACP expression results in a decrease in GBS internalization and translocation across human cervical epithelial cells (ME180). Soluble ACP and its 170 amino acid N-terminal region (NtACP), but not the repeat protein RR′, bind to ME180 cells and reduce internalization of wild-type GBS to levels obtained with an ACP-deficient isogenic mutant. In the current study, ACP colocalized with -integrin, resulting in integrin clustering as determined by laser scanning confocal microscopy. NtACP contains two structural domains, D1 and D2. D1 is structurally similar to fibronectin's integrin-binding region (FnIII10). D1's (KT)D146 motif is structurally similar to the FnIII10 (RG)D1495 integrin-binding motif, suggesting that ACP binds -integrin via the D1 domain. The (KT)D146A mutation within soluble NtACP reduced its ability to bind -integrin and inhibit GBS internalization within ME180 cells. Thus ACP binding to human epithelial cell integrins appears to contribute to GBS internalization within epithelial cells.

  • Received:
  • Accepted:
  • Revised:
  • Published Online:
Keyword(s): ACP, alpha C protein , GAG, glycosaminoglycan , GBS, group B Streptococcus , NtACP, N-terminal domain of ACP and SCPB, GBS C5a peptidase
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2007-12-01
2025-04-18
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The group B streptococcal alpha C protein binds α1β1-integrin through a novel KTD motif that promotes internalization of GBS within human epithelial cells
Microbiology 153, 4039 (2007); https://doi.org/10.1099/mic.0.2007/009134-0
/content/journal/micro/10.1099/mic.0.2007/009134-0
/content/journal/micro/10.1099/mic.0.2007/009134-0
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