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A Variable region within the genome of streptococcus pneumoniae contributes to strain-strain variation in virulence

Harvey, Richard M., Stroeher, Uwe H., Ogunniyi, Abiodun D., Smith-Vaughan, Heidi C., Leach, Amanda J. and Paton, James C. (2011). A Variable region within the genome of streptococcus pneumoniae contributes to strain-strain variation in virulence. PLoS ONE,6(5):e19650.

Document type: Journal Article
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IRMA ID jsingletonxPUB36
NHMRC Grant No. 627142
Title A Variable region within the genome of streptococcus pneumoniae contributes to strain-strain variation in virulence
Author Harvey, Richard M.
Stroeher, Uwe H.
Ogunniyi, Abiodun D.
Smith-Vaughan, Heidi C.
Leach, Amanda J.
Paton, James C.
Journal Name PLoS ONE
Publication Date 2011
Volume Number 6
Issue Number 5
ISSN 1932-6203   (check CDU catalogue open catalogue search in new window)
Start Page e19650
Total Pages 14
Place of Publication United States
Publisher Public Library of Science
HERDC Category C1 - Journal Article (DEST)
Abstract The bacterial factors responsible for the variation in invasive potential between different clones and serotypes of Streptococcus pneumoniae are largely unknown. Therefore, the isolation of rare serotype 1 carriage strains in Indigenous Australian communities provided a unique opportunity to compare the genomes of non-invasive and invasive isolates of the same serotype in order to identify such factors. The human virulence status of non-invasive, intermediately virulent and highly virulent serotype 1 isolates was reflected in mice and showed that whilst both human non-invasive and highly virulent isolates were able to colonize the murine nasopharynx equally, only the human highly virulent isolates were able to invade and survive in the murine lungs and blood. Genomic sequencing comparisons between these isolates identified 8 regions .1 kb in size that were specific to only the highly virulent isolates, and included a version of the pneumococcal pathogenicity island 1 variable region (PPI-1v), phage-associated adherence factors, transporters and metabolic enzymes. In particular, a phage-associated endolysin, a putative iron/lead permease and an operon within PPI-1v exhibited nichespecific changes in expression that suggest important roles for these genes in the lungs and blood. Moreover, in vivo competition between pneumococci carrying PPI-1v derivatives representing the two identified versions of the region showed that the version of PPI-1v in the highly virulent isolates was more competitive than the version from the less virulent isolates in the nasopharyngeal tissue, blood and lungs. This study is the first to perform genomic comparisons between serotype 1 isolates with distinct virulence profiles that correlate between mice and humans, and has highlighted the important role that hypervariable genomic loci, such as PPI-1v, play in pneumococcal disease. The findings of this study have important implications for understanding the processes that drive progression from colonization to invasive disease and will help direct the development of novel therapeutic strategies.
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