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Title: Multi-omics approaches to deciphering a hypervirulent strain of Campylobacter jejuni

item WU, ZUOWEI - Iowa State University
item SAHIN, ORHAN - Iowa State University
item SHEN, ZHANGQI - Iowa State Veterinary Laboratory
item LIU, PENG - Iowa State University
item Miller, William - Bill
item ZHANG, QIJING - Iowa State University

Submitted to: Genome Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/3/2013
Publication Date: 11/6/2013
Citation: Wu, Z., Sahin, O., Shen, Z., Liu, P., Miller, W.G., Zhang, Q. 2013. Multi-omics approaches to deciphering a hypervirulent strain of Campylobacter jejuni. Genome Biology. 5(11):2217-2230.

Interpretive Summary: Campylobacter jejuni is a leading cause of bacterial foodborne gastroenteritis worldwide. Campylobacter infections in humans are characterized by self-limiting watery or bloody diarrhea,abdominal cramps, nausea and fever. Transmission of C. jejuni to humans is mainly via contaminated food of animal origin. In addition, Campylobacter is also a cause of sheep abortion around the globe. Historically, multiple Campylobacter species (primarily C. fetus subsp. fetus) and strains were associated with ovine abortion; however, the proportion of C. jejuni isolates associated with sheep abortion has steadily increased since the late 1980s and outnumbered abortifacient C. fetus subsp. fetus isolates in the United States at the end of last century. To more fully understand the virulence and disease mechanisms of these new emergent sheep abortifacient C. jejuni strains, the genome of a typical C. jejuni sheep abortion strain was sequenced and its genes characterized. Interestingly, the genes present in the sheep abortion strain are highly similar in sequence and content to many other C. jejuni strains that do not cause veterinary issues in sheep. However, 12 variable regions were identified in the sheep abortion strain. Also, analysis of gene expression indicated that some genes were up- or down-regulated when compared to their counterparts in other C.jejuni strains. These genes were primarily in pathways related to iron uptake, amino acid utilization and energy production. These changes in gene expression, as well as the genes present in the 12 variable regions, may contribute to the induction of abortion in sheep.

Technical Abstract: Background: Campylobacter jejuni clone SA recently emerged as the predominant cause of sheep abortion in the U.S. and is also associated with foodborne gastroenteritis in humans. A distinct phenotype of this clone is its ability to induce bacteremia and abortion. To facilitate understanding the pathogenesis of this hypervirulent clone, we analyzed a clinical isolate (IA3902) of clone SA using multi-omics approaches. Results: The genome of IA3902 contains a circular chromosome of 1,635,045 bp and a circular plasmid of 37,174 bp. Comparative genomic analysis revealed that IA3902 is most closely related to C. jejuni NCTC11168, which is a reference strain and was previously shown to be non-abortifacient in pregnant animals. Despite the high genomic synteny and sequence homology, there are 12 variable regions and 8696 SNPs and indels between the two genomes. Notably,the variable genes in the capsular polysaccharides biosynthesis and O-linked glycosylation loci of IA3902 are highly homogenous to their counterparts in C. jejuni subsp. doylei and C. jejuni G1, which are known to be frequently associated with bacteremia Transcriptomic and proteomic profiles were conducted to compare IA3902 with NCTC11168, which revealed that the pathways of energy generation, motility, and serine utilization were significantly up-regulated in IA3902, while the pathways of iron uptake and proline, glutamate, aspartate and lactate utilization were significantly down-regulated.Conclusions: C. jejuni clone SA has evolved distinct genomic content and gene 45 expression patterns that modulate surface polysaccharide structures, motility and metabolic pathways. Collectively, these changes may have contributed to its hyper virulence in abortion induction.