The variable region of the pneumococcal pathogenicity island 1 is responsible for the unusually high virulence of a serotype 1 isolate

Harvey, Richard M. and Trappetti, Claudia and Mahdi, Layla K. and Wang, Hui and McAllister, Lauren J. and Scalvini, Alexandra and Paton, Adrienne W. and Paton, James C. (2016) The variable region of the pneumococcal pathogenicity island 1 is responsible for the unusually high virulence of a serotype 1 isolate. Infection and Immunity, 84 (3). pp. 822-832. ISSN 0019-9567

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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 4496�PPI1 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 4496�PPI1 mutant-infected mice compared to strain 4496-infected mice, the levels of gamma interferon (IFN-�), CXCL10, CCL2, and CCL4 were not different in the two groups. However, the 4496�PPI1 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.

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Published version made accessible in accordance with the copyright policy of the publisher.
Faculty/School / Institute/Centre: No Faculty
Faculty/School / Institute/Centre: No Faculty
Date Deposited: 02 Mar 2017 03:11
Last Modified: 02 Mar 2017 03:11
Uncontrolled Keywords: Streptococcus pneumoniae; mutations; vPPI1; mouse model
Fields of Research (2008): 06 Biological Sciences > 0605 Microbiology > 060501 Bacteriology
10 Technology > 1004 Medical Biotechnology > 100403 Medical Molecular Engineering of Nucleic Acids and Proteins
Fields of Research (2020): 31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310701 Bacteriology
32 BIOMEDICAL AND CLINICAL SCIENCES > 3206 Medical biotechnology > 320603 Medical molecular engineering of nucleic acids and proteins
Socio-Economic Objectives (2008): C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases
C Society > 92 Health > 9204 Public Health (excl. Specific Population Health) > 920407 Health Protection and/or Disaster Response
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