Project description:Background. The bacterial foodborne pathogen Campylobacter jejuni is a common cause of acute gastroenteritis and is also associated with the postinfectious neuropathies, Guillain-Barré and Miller Fisher syndromes. This study described the use of multilocus sequence typing and DNA microarrays to examine the genetic content of a collection of South African C. jejuni strains, recovered from patients with enteritis, Guillain-Barré or Miller Fisher syndromes. Methodology/Principal Findings. The comparative genomic analysis by using multilocus sequence typing and DNA microarrays demonstrated that the South African strains with Penner heat-stable (HS) serotype HS:41 were clearly distinct from the other South African strains. Further analysis of the DNA microarray data demonstrated that the serotype HS:41 strains from South African GBS and enteritis patients are highly similar in gene content. Interestingly, the South African HS:41 strains were distinct in gene content when compared to serotype HS:41 strains from other geographical locations due to the presence of genomic islands, referred to as Campylobacter jejuni integrated elements. Only the genomic integrated element CJIE1, a Campylobacter Mu-like prophage, was present in the South African HS:41 strains whereas absent in the closely-related HS:41 strains from Mexico. A more distantly-related HS:41 strain from Canada possessed both genomic integrated elements CJIE1 and CJIE2. Conclusion/Significance. These findings demonstrated that these C. jejuni integrated elements may contribute to the differentiation of closely-related C. jejuni strains. In addition, the presence of bacteriophage-related genes in CJIE1 may probably contribute to increasing the genomic diversity of these C. jejuni strains. This comparative genomic analysis of the foodborne pathogen C. jejuni provides fundamental information that potentially could lead to improved methods for analyzing the epidemiology of disease outbreaks and their sources. Keywords: comparative genomic indexing analysis

Project description:Prostate cancer (PCa) is a major health problem worldwide with variable incidence, progression and outcomes depending on genetic, environmental and socio-economic factors. This study compares gene expression profiles in PCa patients from South Africa (RSA) and the United States (USA) using RNA sequencing in whole blood and pathway analyses. Whole blood samples were collected in Wren RNA stabilization tubes from RSA-PCa (n=6), RSA-controls (n=6), USA-PCa (n=7) and USA-Controls (n=11). RNA sequencing revealed 1,627 differentially expressed genes (DEGs) in RSA-PCa vs. RSA-controls, and 2,193 DEGs in USA-PCa vs. USA-Controls. Pathway analyses identified geographical region-specific variations; RSA-PCa had upregulated myeloid suppressor cell pathways and immunosuppressive markers while USA-PCa samples exhibited upregulated cytokine signaling and inflammatory pathways. Comparative analysis of healthy controls revealed 2,280 DEGs, which indicated significant differences in molecular profile of the geographic locations. qRT-PCR undertaken on 27 biomarkers related to PCa in whole blood (PROSTest) identified that 26 (96%) of the marker genes were commonly expressed. RNAseq and normalized PCR gene expression of these markers were well-correlated (r=0.44, p=0.0012, n=30 pairs). The results of this study indicate that there are geographic differences in blood-based gene expression in both controls and individuals with PCa. Genes associated with a clinically validated molecular assay (PROSTest) were identified in both populations, but significant differences in gene expression relevant to tumor pathobiology were identified. These immune-associated signaling pathways suggest differences between these two cohorts in blood-based molecular architecture related to PCa. They also suggest the need to consider population-specific biomarkers to better understand this disease. Ultimately, optimizing blood-based molecular diagnostic and therapeutic approaches will require population-level studies. Introduction

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South Africa Prostate Cancer Study

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