Streptococcus pneumoniae biofilm formation is strain dependent, multifactorial, and associated with reduced invasiveness and immunoreactivity during colonization

Krystle Blanchette-Cain, Cecilia A. Hinojosa, Ramya Akula Suresh Babu, Anel Lizcano, Norberto Gonzalez-Juarbe, Carmen Munoz-Almagro, Carlos J. Sanchez, Molly A. Bergman, Carlos J. Orihuela

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Abstract

Biofilms are thought to play an important role during colonization of the nasopharynx by Streptococcus pneumoniae, yet how they form in vivo and the determinants responsible remain unknown. Using scanning electron microscopy, we show that biofilm aggregates of increasing complexity form on murine nasal septa following intranasal inoculation. These biofilms were highly distinct from in vitro biofilms, as they were discontiguous and appeared to incorporate nonbacterial components such as intact host cells. Biofilms initially formed on the surface of ciliated epithelial cells and, as cells were sloughed off, were found on the basement membrane. The size and number of biofilm aggregates within nasal lavage fluid were digitally quantitated and revealed strain-specific capabilities that loosely correlated with the ability to form robust in vitro biofilms. We tested the ability of isogenic mutants deficient in CbpA, pneumolysin, hydrogen peroxide, LytA, LuxS, CiaR/H, and PsrP to form biofilms within the nasopharynx. This analysis revealed that CiaR/H was absolutely required for colonization, that PsrP and SpxB strongly impacted aggregate formation, and that other determinants affected aggregate morphology in a modest fashion. We determined that mice colonized with ΔpsrP mutants had greater levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and KC in nasal lavage fluid than did mice colonized with wild-type controls. This phenotype correlated with a diminished capacity of biofilm pneumococci to invade host cells in vitro despite enhanced attachment. Our results show that biofilms form during colonization and suggest that they may contribute to persistence through a hyperadhesive, noninvasive state that elicits a dampened cytokine response.

Original languageEnglish (US)
Article numbere00745-13
JournalmBio
Volume4
Issue number5
DOIs
StatePublished - Oct 15 2013

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Biofilms
Streptococcus pneumoniae
Nasal Lavage Fluid
Nasopharynx
Cytokines
Nasal Septum
Interleukin-1
Basement Membrane
Electron Scanning Microscopy
Hydrogen Peroxide
Interleukin-6
Tumor Necrosis Factor-alpha
Epithelial Cells
Phenotype

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

Blanchette-Cain, K., Hinojosa, C. A., Akula Suresh Babu, R., Lizcano, A., Gonzalez-Juarbe, N., Munoz-Almagro, C., ... Orihuela, C. J. (2013). Streptococcus pneumoniae biofilm formation is strain dependent, multifactorial, and associated with reduced invasiveness and immunoreactivity during colonization. mBio, 4(5), [e00745-13]. https://doi.org/10.1128/mBio.00745-13

Streptococcus pneumoniae biofilm formation is strain dependent, multifactorial, and associated with reduced invasiveness and immunoreactivity during colonization. / Blanchette-Cain, Krystle; Hinojosa, Cecilia A.; Akula Suresh Babu, Ramya; Lizcano, Anel; Gonzalez-Juarbe, Norberto; Munoz-Almagro, Carmen; Sanchez, Carlos J.; Bergman, Molly A.; Orihuela, Carlos J.

In: mBio, Vol. 4, No. 5, e00745-13, 15.10.2013.

Research output: Contribution to journalArticle

Blanchette-Cain, K, Hinojosa, CA, Akula Suresh Babu, R, Lizcano, A, Gonzalez-Juarbe, N, Munoz-Almagro, C, Sanchez, CJ, Bergman, MA & Orihuela, CJ 2013, 'Streptococcus pneumoniae biofilm formation is strain dependent, multifactorial, and associated with reduced invasiveness and immunoreactivity during colonization', mBio, vol. 4, no. 5, e00745-13. https://doi.org/10.1128/mBio.00745-13
Blanchette-Cain K, Hinojosa CA, Akula Suresh Babu R, Lizcano A, Gonzalez-Juarbe N, Munoz-Almagro C et al. Streptococcus pneumoniae biofilm formation is strain dependent, multifactorial, and associated with reduced invasiveness and immunoreactivity during colonization. mBio. 2013 Oct 15;4(5). e00745-13. https://doi.org/10.1128/mBio.00745-13
Blanchette-Cain, Krystle ; Hinojosa, Cecilia A. ; Akula Suresh Babu, Ramya ; Lizcano, Anel ; Gonzalez-Juarbe, Norberto ; Munoz-Almagro, Carmen ; Sanchez, Carlos J. ; Bergman, Molly A. ; Orihuela, Carlos J. / Streptococcus pneumoniae biofilm formation is strain dependent, multifactorial, and associated with reduced invasiveness and immunoreactivity during colonization. In: mBio. 2013 ; Vol. 4, No. 5.
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abstract = "Biofilms are thought to play an important role during colonization of the nasopharynx by Streptococcus pneumoniae, yet how they form in vivo and the determinants responsible remain unknown. Using scanning electron microscopy, we show that biofilm aggregates of increasing complexity form on murine nasal septa following intranasal inoculation. These biofilms were highly distinct from in vitro biofilms, as they were discontiguous and appeared to incorporate nonbacterial components such as intact host cells. Biofilms initially formed on the surface of ciliated epithelial cells and, as cells were sloughed off, were found on the basement membrane. The size and number of biofilm aggregates within nasal lavage fluid were digitally quantitated and revealed strain-specific capabilities that loosely correlated with the ability to form robust in vitro biofilms. We tested the ability of isogenic mutants deficient in CbpA, pneumolysin, hydrogen peroxide, LytA, LuxS, CiaR/H, and PsrP to form biofilms within the nasopharynx. This analysis revealed that CiaR/H was absolutely required for colonization, that PsrP and SpxB strongly impacted aggregate formation, and that other determinants affected aggregate morphology in a modest fashion. We determined that mice colonized with ΔpsrP mutants had greater levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and KC in nasal lavage fluid than did mice colonized with wild-type controls. This phenotype correlated with a diminished capacity of biofilm pneumococci to invade host cells in vitro despite enhanced attachment. Our results show that biofilms form during colonization and suggest that they may contribute to persistence through a hyperadhesive, noninvasive state that elicits a dampened cytokine response.",
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