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Interkingdom signaling induces Streptococcus pneumoniae biofilm dispersion and transition from asymptomatic colonization to disease

Marks, Laura R; Davidson, Bruce A; Knight, Paul R and Hakansson, Anders P LU (2013) In mBio 4(4). p.13-00438
Abstract

UNLABELLED: Streptococcus pneumoniae is a common human nasopharyngeal commensal colonizing 10% to 40% of healthy individuals, depending on age. Despite a low invasive disease rate, widespread carriage ensures that infection occurs often enough to make S. pneumoniae a leading bacterial cause of respiratory disease worldwide. However, the mechanisms behind transition from asymptomatic colonization to dissemination and disease in otherwise sterile sites remain poorly understood but are epidemiologically strongly linked to infection with respiratory viruses. In this report, we show that infection with influenza A virus and treatment with the resulting host signals (febrile-range temperatures, norepinephrine, extracytoplasmic ATP, and... (More)

UNLABELLED: Streptococcus pneumoniae is a common human nasopharyngeal commensal colonizing 10% to 40% of healthy individuals, depending on age. Despite a low invasive disease rate, widespread carriage ensures that infection occurs often enough to make S. pneumoniae a leading bacterial cause of respiratory disease worldwide. However, the mechanisms behind transition from asymptomatic colonization to dissemination and disease in otherwise sterile sites remain poorly understood but are epidemiologically strongly linked to infection with respiratory viruses. In this report, we show that infection with influenza A virus and treatment with the resulting host signals (febrile-range temperatures, norepinephrine, extracytoplasmic ATP, and increased nutrient availability) induce the release of bacteria from biofilms in a newly developed biofilm model on live epithelial cells both in vitro and during in vivo colonization. These dispersed bacteria have distinct phenotypic properties different from those of both biofilm and broth-grown, planktonic bacteria, with the dispersed population showing differential virulence gene expression characteristics resulting in a significantly increased ability to disseminate and cause infection of otherwise sterile sites, such as the middle ear, lungs, and bloodstream. The results offer novel and important insights into the role of interkingdom signaling between microbe and host during biofilm dispersion and transition to acute disease.

IMPORTANCE: This report addresses the mechanisms involved in transition from pneumococcal asymptomatic colonization to disease. In this study, we determined that changes in the nasopharyngeal environment result in the release of bacteria from colonizing biofilms with a gene expression and virulence phenotype different not only from that of colonizing biofilm bacteria but also from that of the broth-grown planktonic bacteria commonly used for pathogenesis studies. The work importantly also identifies specific host factors responsible for the release of bacteria and their changed phenotype. We show that these interkingdom signals are recognized by bacteria and are induced by influenza virus infection, which is epidemiologically strongly associated with transition to secondary pneumococcal disease. As virus infection is a common inducer of transition to disease among species occupying the nasopharynx, the results of this study may provide a basis for better understanding of the signals involved in the transition from colonization to disease in the human nasopharynx.

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Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Biofilms, Cell Line, Epithelial Cells, Gene Expression, Humans, Mice, Mice, Inbred BALB C, Signal Transduction, Streptococcus pneumoniae, Virulence Factors
in
mBio
volume
4
issue
4
pages
13 - 00438
publisher
American Society for Microbiology
external identifiers
  • Scopus:84883319452
ISSN
2161-2129
DOI
10.1128/mBio.00438-13
language
English
LU publication?
no
id
51cd0204-d890-470c-8ba9-6b0e1e6db0b8
date added to LUP
2016-05-21 10:48:55
date last changed
2017-01-15 04:39:08
@article{51cd0204-d890-470c-8ba9-6b0e1e6db0b8,
  abstract     = {<p>UNLABELLED: Streptococcus pneumoniae is a common human nasopharyngeal commensal colonizing 10% to 40% of healthy individuals, depending on age. Despite a low invasive disease rate, widespread carriage ensures that infection occurs often enough to make S. pneumoniae a leading bacterial cause of respiratory disease worldwide. However, the mechanisms behind transition from asymptomatic colonization to dissemination and disease in otherwise sterile sites remain poorly understood but are epidemiologically strongly linked to infection with respiratory viruses. In this report, we show that infection with influenza A virus and treatment with the resulting host signals (febrile-range temperatures, norepinephrine, extracytoplasmic ATP, and increased nutrient availability) induce the release of bacteria from biofilms in a newly developed biofilm model on live epithelial cells both in vitro and during in vivo colonization. These dispersed bacteria have distinct phenotypic properties different from those of both biofilm and broth-grown, planktonic bacteria, with the dispersed population showing differential virulence gene expression characteristics resulting in a significantly increased ability to disseminate and cause infection of otherwise sterile sites, such as the middle ear, lungs, and bloodstream. The results offer novel and important insights into the role of interkingdom signaling between microbe and host during biofilm dispersion and transition to acute disease.</p><p>IMPORTANCE: This report addresses the mechanisms involved in transition from pneumococcal asymptomatic colonization to disease. In this study, we determined that changes in the nasopharyngeal environment result in the release of bacteria from colonizing biofilms with a gene expression and virulence phenotype different not only from that of colonizing biofilm bacteria but also from that of the broth-grown planktonic bacteria commonly used for pathogenesis studies. The work importantly also identifies specific host factors responsible for the release of bacteria and their changed phenotype. We show that these interkingdom signals are recognized by bacteria and are induced by influenza virus infection, which is epidemiologically strongly associated with transition to secondary pneumococcal disease. As virus infection is a common inducer of transition to disease among species occupying the nasopharynx, the results of this study may provide a basis for better understanding of the signals involved in the transition from colonization to disease in the human nasopharynx.</p>},
  author       = {Marks, Laura R and Davidson, Bruce A and Knight, Paul R and Hakansson, Anders P},
  issn         = {2161-2129},
  keyword      = {Animals,Biofilms,Cell Line,Epithelial Cells,Gene Expression,Humans,Mice,Mice, Inbred BALB C,Signal Transduction,Streptococcus pneumoniae,Virulence Factors},
  language     = {eng},
  number       = {4},
  pages        = {13--00438},
  publisher    = {American Society for Microbiology},
  series       = {mBio},
  title        = {Interkingdom signaling induces Streptococcus pneumoniae biofilm dispersion and transition from asymptomatic colonization to disease},
  url          = {http://dx.doi.org/10.1128/mBio.00438-13},
  volume       = {4},
  year         = {2013},
}