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Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria
Published on: February 23, 2014
Uncovering the link between the SpnIII restriction modification system and LuxS in Streptococcus pneumoniae
Hannah N Agnew1, John M Atack2,3, Ann R D Fernando1
1Research Centre for Infectious Diseases, Department of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA, Australia.
Abstract:
Streptococcus pneumoniae is capable of randomly switching their genomic DNA methylation pattern between six distinct bacterial subpopulations (A-F) via recombination of a type 1 restriction-modification locus, spnIII. These pneumococcal subpopulations exhibit phenotypic changes which favor carriage or invasive disease. In particular, the spnIIIB allele has been associated with increased nasopharyngeal carriage and the downregulation of the luxS gene. The LuxS/AI-2 QS system represent a universal language for bacteria and has been linked to virulence and biofilm formation in S. pneumoniae. In this work, we have explored the link between spnIII alleles, the luxS gene and virulence in two clinical pneumococcal isolates from the blood and cerebrospinal fluid (CSF) of one pediatric meningitis patient. The blood and CSF strains showed different virulence profiles in mice. Analysis of the spnIII system of these strains recovered from the murine nasopharynx showed that the system switched to different alleles commensurate with the initial source of the isolate. Of note, the blood strain showed high expression of spnIIIB allele, previously linked with less LuxS protein production. Importantly, strains with deleted luxS displayed different phenotypic profiles compared to the wildtype, but similar to the strains recovered from the nasopharynx of infected mice. This study used clinically relevant S. pneumoniae strains to demonstrate that the regulatory network between luxS and the type 1 restriction-modification system play a key role in infections and may support different adaptation to specific host niches.
Insights
Streptococcus pneumoniae switches DNA methylation patterns affecting virulence. The spnIII system and luxS gene interact, influencing bacterial adaptation to different host environments like nasopharynx and bloodstream.
Area of Science:
- Microbiology
- Genetics
- Bacterial Pathogenesis
Background:
- Streptococcus pneumoniae exhibits DNA methylation pattern switching via the spnIII locus, creating subpopulations (A-F).
- Specific spnIII alleles, like spnIIIB, correlate with increased nasopharyngeal carriage and reduced luxS gene expression.
- The LuxS/AI-2 quorum sensing (QS) system is crucial for bacterial communication, virulence, and biofilm formation.
Purpose of the Study:
- To investigate the interplay between spnIII alleles, luxS gene expression, and virulence in clinical Streptococcus pneumoniae isolates.
- To understand how these regulatory networks influence bacterial adaptation to distinct host niches during infection.
Main Methods:
- Analysis of two clinical Streptococcus pneumoniae isolates from a pediatric meningitis patient (blood and CSF).
- Assessment of virulence profiles in murine models.
- Examination of spnIII system dynamics and luxS gene expression in strains recovered from infected murine nasopharynx.
- Phenotypic comparison of wildtype strains with luxS-deleted mutants.
Main Results:
- Clinical isolates displayed varying virulence profiles in mice.
- SpnIII alleles switched in strains recovered from the murine nasopharynx, correlating with the isolate's origin.
- The blood isolate showed high spnIIIB expression, linked to lower LuxS production.
- Strains with deleted luxS exhibited altered phenotypes, resembling nasopharyngeal isolates.
Conclusions:
- A regulatory network exists between the luxS gene and the type 1 restriction-modification system (spnIII) in Streptococcus pneumoniae.
- This network plays a significant role in pneumococcal infections.
- The system facilitates adaptation to specific host niches, impacting disease dynamics.
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