Monday, 16 November 2009

Campylobacter source attribution in New Zealand

What is the source of the common food poisoning pathogen Campylobacter jejuni was the subject of a paper published in September last year in PLoS Genetics by my colleagues and I, in which we traced the origin of bacterial isolates collected from patients in Lancashire, England. In that study, and a subsequent investigation into campylobacteriosis across Scotland, we found that the majority of cases could be attributed to populations of C. jejuni typically found in poultry.

Now Petra Mullner, Nigel French and colleagues have genetically characterized the C. jejuni populations found in human patients, cattle, sheep, poultry and environmental samples from New Zealand covering the period March 2005 - February 2008. What is special about their study is that the New Zealand poultry industry is a closed system, with no foreign imports, making it possible to directly sample the putative source populations and disease-causing isolates concurrently.

Like the studies in England and Scotland, poultry was the inferred source of the majority of disease in New Zealand. Uniquely however, it was possible to attribute cases separately to the three major poultry suppliers on the islands. One supplier in particular was attributed a disproportionate number of cases using 3 assignment methods, including my method (iSource, soon to be available on this website). Supported in part by this evidence, the New Zealand Food Safety Authority introduced mandatory targets for limiting Campylobacter contamination of poultry products in 2007. Remarkably, the number of cases fell from 15,873 in 2006 before the control measures were introduced to 6,689 in 2008. The next chapter of this intriguing story will be a follow-up study to establish whether the fall in the number of cases corresponded to a reduction in the proportion of campylobacteriosis attributable to poultry sources.

Selection in a putative meningitis vaccine target

In Variation of the factor H-binding protein in Neisseria meningitidis, Carina Brehony in Martin Maiden's lab at Oxford investigated a group of outer membrane proteins in the bacterium responsible for meningococcal meningitis. To date, attempts to raise a vaccine against the common serogroup B meningococci have been frustrated by the low immunogenicity of the serogroup B capsular polysaccharide, despite success with serogroups A and C. Outer membrane proteins, such as factor H-binding protein (fHbp) may provide alternative targets for vaccine development.

However, fHbp is genetically diverse, and our investigation showed evidence of structuring into three groups. OmegaMap analyses of the three groups revealed a signature consistent with strong selection pressure for antigenic variability at the gene. Notably, there was clear evidence of diversifying selection at several previously discovered epitopes - positions in the protein targeted by antibodies during bacteria-killing immune response. (Analysis of one group is shown in the figure, with known epitopes marked).

While these observations are encouraging in terms of understanding the biology of pathogen antigens, a pressing question is how do we translate that understanding into practical vaccine design? Studies such as ours suggest a multi-component vaccine may be necessary to achieve broad coverage against serogroup B meningococci.

Recombination and proper segregation in human meiosis

My blog entries have lapsed since the summer while I have attempted to press on with various projects to tie up as much as possible by the end of the year. Meanwhile, my collaborators and I have had three papers published.

In Broad-scale recombination patterns underlying proper disjunction in humans, Adi Alon and colleagues have used a large Hutterite pedigree to test two molecular hypotheses in a statistical genetics fashion. Crossing-over is important for proper segregation of chromosomes during meiosis. When chromosomes fail to segregate properly, the result is aneuploidy, a genetic pathology underlying many inherited diseases; for example, aneuploidy at chromosome 21 is often the basis of Down's syndrome.

It has been suggested that a hard limit of at least one crossover per chromosome is necessary for correct disjunction; others have suggested the requirement is for one crossover per chromosome arm. By reconstructing the probable distribution of the number of crossovers during meiosis, we were able to show that proper disjunction frequently occurs in humans in the absence of a crossover every chromosome arm. Further, the evidence suggested that successful segregation of some chromosomes can occur without a crossover at all - interestingly chromosome 21 was flagged up among others. This leads to the question, is there a back-up cellular mechanism to rescue meiotic division when crossovers fail to form?