Function of BriC peptide in the pneumococcal competence and virulence portfolio.
Streptococcus pneumoniae (pneumococcus) is an opportunistic pathogen that causes otitis media, sinusitis, pneumonia, meningitis and sepsis. The progression to this pathogenic lifestyle is preceded by asymptomatic colonization of the nasopharynx. This colonization is associated with biofilm formation...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2018-10-01
|
Series: | PLoS Pathogens |
Online Access: | https://doi.org/10.1371/journal.ppat.1007328 |
id |
doaj-4124728df49c4f7db9a7031cbc7af6f0 |
---|---|
record_format |
Article |
spelling |
doaj-4124728df49c4f7db9a7031cbc7af6f02021-04-21T17:03:50ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742018-10-011410e100732810.1371/journal.ppat.1007328Function of BriC peptide in the pneumococcal competence and virulence portfolio.Surya D AggarwalRory EutseyJacob West-RobertsArnau DomenechWenjie XuIman Tajer AbdullahAaron P MitchellJan-Willem VeeningHasan YesilkayaN Luisa HillerStreptococcus pneumoniae (pneumococcus) is an opportunistic pathogen that causes otitis media, sinusitis, pneumonia, meningitis and sepsis. The progression to this pathogenic lifestyle is preceded by asymptomatic colonization of the nasopharynx. This colonization is associated with biofilm formation; the competence pathway influences the structure and stability of biofilms. However, the molecules that link the competence pathway to biofilm formation are unknown. Here, we describe a new competence-induced gene, called briC, and demonstrate that its product promotes biofilm development and stimulates colonization in a murine model. We show that expression of briC is induced by the master regulator of competence, ComE. Whereas briC does not substantially influence early biofilm development on abiotic surfaces, it significantly impacts later stages of biofilm development. Specifically, briC expression leads to increases in biofilm biomass and thickness at 72h. Consistent with the role of biofilms in colonization, briC promotes nasopharyngeal colonization in the murine model. The function of BriC appears to be conserved across pneumococci, as comparative genomics reveal that briC is widespread across isolates. Surprisingly, many isolates, including strains from clinically important PMEN1 and PMEN14 lineages, which are widely associated with colonization, encode a long briC promoter. This long form captures an instance of genomic plasticity and functions as a competence-independent expression enhancer that may serve as a precocious point of entry into this otherwise competence-regulated pathway. Moreover, overexpression of briC by the long promoter fully rescues the comE-deletion induced biofilm defect in vitro, and partially in vivo. These findings indicate that BriC may bypass the influence of competence in biofilm development and that such a pathway may be active in a subset of pneumococcal lineages. In conclusion, BriC is a part of the complex molecular network that connects signaling of the competence pathway to biofilm development and colonization.https://doi.org/10.1371/journal.ppat.1007328 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Surya D Aggarwal Rory Eutsey Jacob West-Roberts Arnau Domenech Wenjie Xu Iman Tajer Abdullah Aaron P Mitchell Jan-Willem Veening Hasan Yesilkaya N Luisa Hiller |
spellingShingle |
Surya D Aggarwal Rory Eutsey Jacob West-Roberts Arnau Domenech Wenjie Xu Iman Tajer Abdullah Aaron P Mitchell Jan-Willem Veening Hasan Yesilkaya N Luisa Hiller Function of BriC peptide in the pneumococcal competence and virulence portfolio. PLoS Pathogens |
author_facet |
Surya D Aggarwal Rory Eutsey Jacob West-Roberts Arnau Domenech Wenjie Xu Iman Tajer Abdullah Aaron P Mitchell Jan-Willem Veening Hasan Yesilkaya N Luisa Hiller |
author_sort |
Surya D Aggarwal |
title |
Function of BriC peptide in the pneumococcal competence and virulence portfolio. |
title_short |
Function of BriC peptide in the pneumococcal competence and virulence portfolio. |
title_full |
Function of BriC peptide in the pneumococcal competence and virulence portfolio. |
title_fullStr |
Function of BriC peptide in the pneumococcal competence and virulence portfolio. |
title_full_unstemmed |
Function of BriC peptide in the pneumococcal competence and virulence portfolio. |
title_sort |
function of bric peptide in the pneumococcal competence and virulence portfolio. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2018-10-01 |
description |
Streptococcus pneumoniae (pneumococcus) is an opportunistic pathogen that causes otitis media, sinusitis, pneumonia, meningitis and sepsis. The progression to this pathogenic lifestyle is preceded by asymptomatic colonization of the nasopharynx. This colonization is associated with biofilm formation; the competence pathway influences the structure and stability of biofilms. However, the molecules that link the competence pathway to biofilm formation are unknown. Here, we describe a new competence-induced gene, called briC, and demonstrate that its product promotes biofilm development and stimulates colonization in a murine model. We show that expression of briC is induced by the master regulator of competence, ComE. Whereas briC does not substantially influence early biofilm development on abiotic surfaces, it significantly impacts later stages of biofilm development. Specifically, briC expression leads to increases in biofilm biomass and thickness at 72h. Consistent with the role of biofilms in colonization, briC promotes nasopharyngeal colonization in the murine model. The function of BriC appears to be conserved across pneumococci, as comparative genomics reveal that briC is widespread across isolates. Surprisingly, many isolates, including strains from clinically important PMEN1 and PMEN14 lineages, which are widely associated with colonization, encode a long briC promoter. This long form captures an instance of genomic plasticity and functions as a competence-independent expression enhancer that may serve as a precocious point of entry into this otherwise competence-regulated pathway. Moreover, overexpression of briC by the long promoter fully rescues the comE-deletion induced biofilm defect in vitro, and partially in vivo. These findings indicate that BriC may bypass the influence of competence in biofilm development and that such a pathway may be active in a subset of pneumococcal lineages. In conclusion, BriC is a part of the complex molecular network that connects signaling of the competence pathway to biofilm development and colonization. |
url |
https://doi.org/10.1371/journal.ppat.1007328 |
work_keys_str_mv |
AT suryadaggarwal functionofbricpeptideinthepneumococcalcompetenceandvirulenceportfolio AT roryeutsey functionofbricpeptideinthepneumococcalcompetenceandvirulenceportfolio AT jacobwestroberts functionofbricpeptideinthepneumococcalcompetenceandvirulenceportfolio AT arnaudomenech functionofbricpeptideinthepneumococcalcompetenceandvirulenceportfolio AT wenjiexu functionofbricpeptideinthepneumococcalcompetenceandvirulenceportfolio AT imantajerabdullah functionofbricpeptideinthepneumococcalcompetenceandvirulenceportfolio AT aaronpmitchell functionofbricpeptideinthepneumococcalcompetenceandvirulenceportfolio AT janwillemveening functionofbricpeptideinthepneumococcalcompetenceandvirulenceportfolio AT hasanyesilkaya functionofbricpeptideinthepneumococcalcompetenceandvirulenceportfolio AT nluisahiller functionofbricpeptideinthepneumococcalcompetenceandvirulenceportfolio |
_version_ |
1714666592546062336 |