Monitoring the Long-Term Molecular Epidemiology of the Pneumococcus and Detection of Potential ‘Vaccine Escape’ StrainsReportar como inadecuado




Monitoring the Long-Term Molecular Epidemiology of the Pneumococcus and Detection of Potential ‘Vaccine Escape’ Strains - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Background

While the pneumococcal protein conjugate vaccines reduce the incidence in invasive pneumococcal disease IPD, serotype replacement remains a major concern. Thus, serotype-independent protection with vaccines targeting virulence genes, such as PspA, have been pursued. PspA is comprised of diverse clades that arose through recombination. Therefore, multi-locus sequence typing MLST-defined clones could conceivably include strains from multiple PspA clades. As a result, a method is needed which can both monitor the long-term epidemiology of the pneumococcus among a large number of isolates, and analyze vaccine-candidate genes, such as pspA, for mutations and recombination events that could result in ‘vaccine escape’ strains.

Methodology

We developed a resequencing array consisting of five conserved and six variable genes to characterize 72 pneumococcal strains. The phylogenetic analysis of the 11 concatenated genes was performed with the MrBayes program, the single nucleotide polymorphism SNP analysis with the DNA Sequence Polymorphism program DnaSP, and the recombination event analysis with the recombination detection package RDP.

Results

The phylogenetic analysis correlated with MLST, and identified clonal strains with unique PspA clades. The DnaSP analysis correlated with the serotype-specific diversity detected using MLST. Serotypes associated with more than one ST complex had a larger degree of sequence polymorphism than a serotype associated with one ST complex. The RDP analysis confirmed the high frequency of recombination events in the pspA gene.

Conclusions

The phylogenetic tree correlated with MLST, and detected multiple PspA clades among clonal strains. The genetic diversity of the strains and the frequency of recombination events in the mosaic gene, pspA were accurately assessed using the DnaSP and RDP programs, respectively. These data provide proof-of-concept that resequencing arrays could play an important role within research and clinical laboratories in both monitoring the molecular epidemiology of the pneumococcus and detecting ‘vaccine escape’ strains among vaccine-candidate genes.



Autor: Gagan A. Pandya , M. Catherine McEllistrem , Pratap Venepally, Michael H. Holmes, Behnam Jarrahi, Ravi Sanka, Jia Liu, Svetlana A

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados