title: The Variable Region of Pneumococcal Pathogenicity Island 1 Is Responsible for Unusually High Virulence of a Serotype 1 Isolate.
abstract: Streptococcus pneumoniae is the leading infectious cause of death in children in the world. However, the mechanisms that drive the progression from asymptomatic colonization to disease are poorly understood. Two virulence-associated genomic accessory regions (ARs) were deleted in a highly virulent serotype 1 clinical isolate (strain 4496) and examined for their contribution to pathogenesis. Deletion of a prophage encoding a platelet-binding protein (PblB) resulted in reduced adherence, biofilm formation, reduced initial infection within the lungs, and a reduction in the number of circulating platelets in infected mice. However, the region's overall contribution to the survival of mice was not significant. In contrast, deletion of the variable region of pneumococcal pathogenicity island 1 (vPPI1) was also responsible for a reduction in adherence and biofilm formation but also reduced survival and invasion of the pleural cavity, blood, and lungs. While the 4496ΔPPI1 strain induced higher expression of the genes encoding interleukin-10 (IL-10) and CD11b in the lungs of challenged mice than the wild-type strain, very few other genes exhibited altered expression. Moreover, while the level of IL-10 protein was increased in the lungs of 4496ΔPPI1 mutant-infected mice compared to strain 4496-infected mice, the levels of gamma interferon (IFN-γ), CXCL10, CCL2, and CCL4 were not different in the two groups. However, the 4496ΔPPI1 mutant was found to be more susceptible than the wild type to phagocytic killing by a macrophage-like cell line. Therefore, our data suggest that vPPI1 may be a major contributing factor to the heightened virulence of certain serotype 1 strains, possibly by influencing resistance to phagocytic killing.
authors.affiliation: Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, University of Adelaide, S.A., Australia.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Harvey
authors.affiliation: Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, University of Adelaide, S.A., Australia.
authors.forename: Claudia
authors.initials: C
authors.lastname: Trappetti
authors.affiliation: Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, University of Adelaide, S.A., Australia.
authors.forename: Layla K
authors.initials: LK
authors.lastname: Mahdi
authors.affiliation: Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, University of Adelaide, S.A., Australia.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, University of Adelaide, S.A., Australia.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: McAllister
authors.affiliation: Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, University of Adelaide, S.A., Australia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Scalvini
authors.affiliation: Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, University of Adelaide, S.A., Australia.
authors.forename: Adrienne W
authors.initials: AW
authors.lastname: Paton
authors.affiliation: Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, University of Adelaide, S.A., Australia james.paton@adelaide.edu.au.
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D044404:Genomic Islands; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011008:Pneumococcal Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D016753:Interleukin-10