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Dynamic changes in the Streptococcus pneumoniae transcriptome during transition from biofilm formation to invasive disease upon influenza A virus infection

Pettigrew, Melinda M; Marks, Laura R; Kong, Yong; Gent, Janneane F; Roche-Hakansson, Hazeline and Hakansson, Anders P LU (2014) In Infection and Immunity 82(11). p.19-4607
Abstract

Streptococcus pneumoniae is a leading cause of infectious disease globally. Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior studies have indicated that biofilm-derived pneumococci are avirulent. However, influenza A virus (IAV) infection releases virulent pneumococci from biofilms in vitro and in vivo. Triggers of dispersal include IAV-induced changes in the nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare the S. pneumoniae transcriptome in biofilms, bacteria dispersed from biofilms after exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at 37°C. Compared with biofilm... (More)

Streptococcus pneumoniae is a leading cause of infectious disease globally. Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior studies have indicated that biofilm-derived pneumococci are avirulent. However, influenza A virus (IAV) infection releases virulent pneumococci from biofilms in vitro and in vivo. Triggers of dispersal include IAV-induced changes in the nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare the S. pneumoniae transcriptome in biofilms, bacteria dispersed from biofilms after exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at 37°C. Compared with biofilm bacteria, actively dispersed S. pneumoniae, which were more virulent in invasive disease, upregulated genes involved in carbohydrate metabolism. Enzymatic assays for ATP and lactate production confirmed that dispersed pneumococci exhibited increased metabolism compared to those in biofilms. Dispersed pneumococci also upregulated genes associated with production of bacteriocins and downregulated colonization-associated genes related to competence, fratricide, and the transparent colony phenotype. IAV had the largest impact on the pneumococcal transcriptome. Similar transcriptional differences were also observed when actively dispersed bacteria were compared with avirulent planktonic bacteria. Our data demonstrate complex changes in the pneumococcal transcriptome in response to IAV-induced changes in the environment. Our data suggest that disease is caused by pneumococci that are primed to move to tissue sites with altered nutrient availability and to protect themselves from the nasopharyngeal microflora and host immune response. These data help explain pneumococcal virulence after IAV infection and have important implications for studies of S. pneumoniae pathogenesis.

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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, Tumor, Epithelial Cells, Humans, Influenza A virus, Mice, Mice, Inbred BALB C, Orthomyxoviridae Infections, Pneumococcal Infections, Reverse Transcriptase Polymerase Chain Reaction, Sepsis, Streptococcus pneumoniae
in
Infection and Immunity
volume
82
issue
11
pages
13 pages
publisher
American Society for Microbiology
external identifiers
  • Scopus:84907960253
ISSN
1098-5522
DOI
10.1128/IAI.02225-14
language
English
LU publication?
no
id
7ac570c6-ab88-4ca9-8850-f9f18a76ad67
date added to LUP
2016-05-20 17:57:33
date last changed
2016-11-06 04:38:04
@misc{7ac570c6-ab88-4ca9-8850-f9f18a76ad67,
  abstract     = {<p>Streptococcus pneumoniae is a leading cause of infectious disease globally. Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior studies have indicated that biofilm-derived pneumococci are avirulent. However, influenza A virus (IAV) infection releases virulent pneumococci from biofilms in vitro and in vivo. Triggers of dispersal include IAV-induced changes in the nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare the S. pneumoniae transcriptome in biofilms, bacteria dispersed from biofilms after exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at 37°C. Compared with biofilm bacteria, actively dispersed S. pneumoniae, which were more virulent in invasive disease, upregulated genes involved in carbohydrate metabolism. Enzymatic assays for ATP and lactate production confirmed that dispersed pneumococci exhibited increased metabolism compared to those in biofilms. Dispersed pneumococci also upregulated genes associated with production of bacteriocins and downregulated colonization-associated genes related to competence, fratricide, and the transparent colony phenotype. IAV had the largest impact on the pneumococcal transcriptome. Similar transcriptional differences were also observed when actively dispersed bacteria were compared with avirulent planktonic bacteria. Our data demonstrate complex changes in the pneumococcal transcriptome in response to IAV-induced changes in the environment. Our data suggest that disease is caused by pneumococci that are primed to move to tissue sites with altered nutrient availability and to protect themselves from the nasopharyngeal microflora and host immune response. These data help explain pneumococcal virulence after IAV infection and have important implications for studies of S. pneumoniae pathogenesis.</p>},
  author       = {Pettigrew, Melinda M and Marks, Laura R and Kong, Yong and Gent, Janneane F and Roche-Hakansson, Hazeline and Hakansson, Anders P},
  issn         = {1098-5522},
  keyword      = {Animals,Biofilms,Cell Line, Tumor,Epithelial Cells,Humans,Influenza A virus,Mice,Mice, Inbred BALB C,Orthomyxoviridae Infections,Pneumococcal Infections,Reverse Transcriptase Polymerase Chain Reaction,Sepsis,Streptococcus pneumoniae},
  language     = {eng},
  number       = {11},
  pages        = {19--4607},
  publisher    = {ARRAY(0x9d68cd8)},
  series       = {Infection and Immunity},
  title        = {Dynamic changes in the Streptococcus pneumoniae transcriptome during transition from biofilm formation to invasive disease upon influenza A virus infection},
  url          = {http://dx.doi.org/10.1128/IAI.02225-14},
  volume       = {82},
  year         = {2014},
}