Genome Sequencing of Atypical Disease-associated and Emerging Infectious Disease Isolates of the Biodefense Category B Food and Water Borne Priority Pathogen Campylobacter Jejuni, and Related Species

Genome Sequencing of Atypical Disease-associated and Emerging Infectious Disease Isolates of the Biodefense Category B Food and Water Borne Priority Pathogen Campylobacter Jejuni, and Related Species

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This project is complete.

Goals

The genomes of five well-characterized Campylobacter jejuni subsp. jejunistrains will be sequenced to 8-fold coverage and the genomes of four emerging infectious isolates of Campylobacter and the only known commensal of Campylobacter will be completed. This work will significantly expand and complement the Campylobacter comparative genome project that was completed in 2005. The strains we have chosen for sequencing possess significant genetic differences that influence their pathogenic potential or constitute a non-pathogenic reference for in silico genomic subtraction. The variety of diseases caused and virulence capabilities of these strains underscores the diversity within the species. It is anticipated that this wealth of information will help address fundamental questions about the genomic basis of Guillain-Barre syndrome (GBS) and Miller-Fisher syndrome (MFS), of pathogenesis of atypical/extraintestinal and emerging C. jejuni strains, of the diversity of Campylobacter spp. (and virulence mechanisms) causing human illness, and to determine the extent of gene transfer among Campylobacterspp., resulting in the emergence of non-C. jejuni subsp. jejuni infectious agents. Furthermore, this data will aid in forensic analysis in cases of bioterrorism by facilitating the generation of detection systems and supply targets for vaccine development.

Isolates

Strain selection was preformed after consultation with the Campylobacterscientific community resulting in the selection of ten Campylobacter strains that are targeted for genomic sequencing. Analysis of the genomic data will allow for examination of genetic differences, including gross chromosomal changes and individual polymorphisms, and their correlation to disease progression and outcomes caused by this important biodefense agent.

Projects

Campylobacter concisus 13826

Strains of this species were first isolated from gingival crevices of persons with gingivitis, periodontitis, and periodontosis, but have subsequently been isolated from the feces of patients with gastroenteritis. This strain was isolated in Denmark from the feces of a patient with bloody diarrhea. No sequence is available for this Campylobacter species. The complete genome sequence of this isolate may enable identification of possible mechanisms for the ability of Campylobacter to cause diarrhea and any horizontal transfer events from C. jejuni or C. coli, more common diarrhea-causing Campylobacter species. Perhaps we can determine how this species is emerging as a gastrointestinal infectious agent from the complete genomic sequence.

Campylobacter curvus 525.92

Like C. concisus, this Campylobacter species has been historically associated with periodontal disease, but has been recently isolated from human patients with gastroenteritis. This strain was isolated in South Africa from the feces of a patient with diarrhea. It will be very interesting to compare the genomic sequence of this strain to the genome of C. concisus. Genes or pathways shared between C. curvus and C. concisus might reveal mechanisms for causing gastroenteritis or periodontal disease. As with C. concisus, we might be able to explain common mechanisms for their emergence as human gastrointestinal infectious agents.

Campylobacter fetus subsp. fetus 82-40

This is a serotype of C. fetus subsp fetus isolated from the blood of a human patient who was having a renal transplant. The ratio of bloodstream infection to diarrheal illnesses for C. fetus is nearly 400-fold higher than for C. jejuni, indicating its marked propensity for invasive disease compared to C. jejuni. This strain was chosen because it is the best characterized human C. fetus isolate.

Campylobacter hominis ATCC BAA-381

This is the only known species of Campylobacter that is not pathogenic to humans. It is the type strain that was isolated in 2001 from the feces of a healthy human. The complete sequence of this strain will be very useful for subtracting all the genes involved in survival in the human gut and attachment to intestinal epithelial cells, which will facilitate identification of novel genes in the pathogenic species.

Campylobacter jejuni subsp. doylei 269.97

This strain is a representative of the C. jejuni subsp. doylei that causes bacteremia in South Africa. At the Red Cross Children's hospital in Cape Town South Africa, C. jejuni subsp. doylei has been isolated from the blood more frequently than C. jejuni subsp. jejuni. The complete genomic sequence (none available at present) for C. jejuni subsp. doylei will reveal the differences between C. jejuni subsp. doylei and C. jejuni subsp. jejuni and may help determine why these emerging C. jejuni subsp. doylei isolates cause more blood-borne disease than C. jejuni subsp. jejuni.

Campylobacter jejuni subsp. jejuni 260.94

This is a representative of the clonal population of Penner serotype O:41 GBS-associated Campylobacter strains from the Red Cross Children's Hospital in Cape Town, South Africa. It has been associated with the acute inflammatory demyelinating polyneuropathy (AIDP) form of GBS, which is the most common form of GBS. This strain has been compared with HB93-13 in a previous study. It has been shown to express the GM1 ganglioside-like structure. This strain was chosen because it is part of the second known overrepresented serotype that is highly associated with GBS.

Campylobacter jejuni subsp. jejuni 81-176

This is the best characterized C. jejuni strain and one that has caused disease in 2 human volunteer studies. It was originally isolated from the feces of an 9-year-old girl with diarrhea as the result of an outbreak of Campylobacteriosis associated with the consumption of raw milk on a dairy farm in Minnesota, USA during a third grade class field trip in 1981. It was passaged through human volunteer trials by Black et al., in 1987 and passaged again by Dr. Patricia Guerry's group, where it is proven to still cause human gastroenteritis. It is virulent in Rhesus macaques, ferrets, intranasally in mice, and colostrum-deprived piglets. The strain invades intestinal epithelial cells at levels that are as much as 3 logs higher than other invasive strains.

Campylobacter jejuni subsp. jejuni 84-25

This strain was isolated in the USA from the cerebrospinal fluid of a child with meningitis. This strain is of interest because it represents a C. jejuni strain that can go systemic. It is also auxotrophic (Met- Ser- and requires cysteine and cystine). The sequence of this isolate might reveal previously unknown mechanisms for non-gastrointestinal tropism(s).

Campylobacter jejuni subsp. jejuni CF93-6

This is a representative strain isolated in Japan from a patient diagnosed with MFS. It has been recently shown to produce a GT1a-like ganglioside mimic that is cross-reactive to anti-GQ1b antibodies.

Campylobacter jejuni subsp. jejuni HB93-13

This is a well characterized strain that was isolated from the feces of an 8-year-old boy in China that was diagnosed with the acute motor axonal neuropathy (AMAN) form of GBS. It is of Penner serotype O:19, which is overrepresented among GBS-associated serotypes in certain parts of the world. It has been shown to express the GM1 and GD1a ganglioside-like structures. Many different labs study this strain.

Data Access