Genome comparison points to why bacteria becomes lethal

AUG. 14–NEW YORK–Looking closely into the iris-shaped map of a microbial genome, the Sanger Institute’s Julian Parkhill sees more than just sequence, Genomeweb.com reports.

When he compares this slivered circle of sequence to those of closely related genomes he starts to discern the story of the organism’s molecular evolution.

Most recently, Parkhill and colleagues have traced this evolution by sequencing the Bortedella pertussis, the organism that causes whooping cough, along with two related pathogenic bacteria, Bortedella parapertussis and Bortadella bronchiseptica, and comparing the sequences in a paper published online in Nature Genetics.

“Our data indicate that at the genetic level, B. pertussis and B. parapertussis each derived from a B. bronchiseptica-like ancestor,” the authors wrote.

Parkhill’s group has conducted similar comparative sequence analysis on Salmonella typhii and a related genome, S. typhimurium; as well as Yersinia Pestis and closely related species of Yersinia spp, Parkhill said at a genomics conference in late May at Cold Spring Harbor Labs.

These genomic comparisons not only demonstrate what is possible when multiple closely-related species are sequenced-something that researchers in other areas from Drosophila to primates are lobbying to have done. They also shed light on a key scientific question with implications for public health and medicine: why do bacteria become human pathogens?

In the case Bordatella species comparisons, Parkhill and colleagues found that there had been a number of gene deletions in B. pertussis, making its genome smaller, along with “enormous expansion of selfish, mobile elements,” Parkhill said at the Cold Spring Harbor conference.

“It may be that B. pertussis followed this evolutionary path owing to the opportunities for increased transmission rate provided by the increase in size and density of the populations of its specific host, Homo sapiens,” the authors wrote in the Nature paper.

With bacteria, there is an evolutionary trade-off between virulence and transmissibility-the more virulent a pathogen becomes, the less transmissible, as the host is less likely to survive to pass it on, Parkhill said at the Cold Spring Harbor meeting. But in the case of B. pertussis, he and his colleagues believe the evolutionarily recent increase in human population density may have made that dilemma a bit easier for the organism-leading it to evolve to become more virulent within the narrow niche of its human host, while discarding the elements that enable related species to infect multiple hosts and be transmitted more easily from host to host.

Parkhill and colleagues found a similar pattern in comparing the genomes of S. typhii to S. typhimurium: These comparisons indicate that S. typhimurim, a broad gut organism with many hosts, appears to have evolved over the past 40,000 years into the more systemic pathogen (the cause of typhoid) with one (human) host.

In other words, human urbanization may have in fact led the bacteria to become more pathogenic, rather than merely serving as a mechanism for an existing pathogen to spread more rapidly.

If this hypotheses proves correct, it is one that could apply to currently emerging infectious diseases as well, said Parkhill, as human populations are only becoming more dense–and bacteria are likely to be evolving along with them.

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