Some microbiologists relish each new firehose burst of data, holding their ground and expecting to learn something new and wondrous from each successive soaking. The optimists who adhere to this strategy declare that there surely will be something useful- a new pathogen, a sign of incipient infectious disease, perhaps even the signature of a bioterrorist attack- amid the torrents of potentially extraneous information. Maybe they will prove to be correct. For now, it was impressive hearing about some of their promising efforts during the 8th ASM Biodefense and Emerging Diseases Research Meeting, held in Baltimore, Md., last February.

One such approach entails "listening" to the host by monitoring gene expression patterns during infections, including at their earliest phases, according to David Relman of Stanford University in Palo Alto, Calif., who spoke during the plenary session, "Impacts of Genomics on Bioterrorism Preparedness." Microarrays that look at gene transcript abundances provide a direct way to look at how hosts respond to diseases, including infections and cancer, he says.

However, the signs of infectious processes prove far more varied and "polymorphic" than do those even for cancer, making analysis "tougher," Relman continues. An individual's prior exposures to pathogens, which cells and tissues in the body are being examined, gender and age, time of day, and other factors contribute to the analytic complexity.

Nonetheless, in some cases, gene transcript patterns can prove useful for monitoring specific, infection-associated processes. For instance, although there is no "corroborated etiologic agent" for causing Kawasaki syndrome in children, this form of vasculitis yields a "distinct pattern" of transcripts, particularly among interferon response genes, when compared to other similar diseases affecting chil dren, Relman says. That pattern might prove useful for recognizing ongoing Kawasaki and then guiding treatments with immunoglobulins, which prove critical for a fraction of children with that syndrome who are at risk for developing potentially lethal coronary aneurysms, he says.

About two years ago, W. Ian Lipkin of Columbia University in New York, N.Y., and his collaborators used genomic analysis to show there is no causal link between autism and use of the measles, mumps, and rubella vaccine (Microbe, November 2008, p. 508). What does give rise to autism remains an open question, he pointed out during another plenary session in February, "From Zoonosis to Pandemics."

One noteworthy finding is that children with autism show "dramatic reductions" in enzymes that digest sugars, Lipkin continues. Moreover, there is a shift in the gut microflora of these children, including the appearance of a novel species of bacteria within that microbial community, and also evidence of damage along the intestinal surface that seems consistent with malabsorption of sugars among this group of children. If these observations hold up, they raise the possibility that autism could be either prevented or possibly corrected by countering such changes in the microflora of children with probiotics, antibiotics, or changes in diets, he points out.

Thomas Briese, who spoke in the same session as Relman and who is Lipkin's colleague at Columbia, describes an approach to diagnosing infectious disease agents that depends on comprehensive DNA sequencing. Simply put, it consists of "sequencing everything, then looking at non-host segments and going from there," he says. The key to this wholesale DNAsmashing approach is "pattern-recognition software" that will reliably pick up "uncharacteristic sequences"-in this case, those that arise from microbial pathogens of one sort or another. This approach proved critical several years ago, for example, for identifying a novel virus from the gastrointestinal tracts and brains of parrots, Briese says.

David Wang of Washington University School of Medicine in St. Louis, Mo., speaking during the same session, also favors a panoramic DNA sequencing approach, particularly to identify novel viruses as candidate pathogens. For instance, he and his collaborators recently identified several novel types of astroviruses from human stool specimens collected from patients with diarrhea in India.

Whether those viruses are truly pathogenic or mere bystanders remains to be determined. "There's nothing to argue these are the bona fide [infectious disease] agents yet," Wang says. Nonetheless, sequencing offers a powerful means for finding novel viral signatures, he adds. "DNA sequencing is more comprehensive and less biased than traditional methods."

Jeffrey L. Fox
Jeffrey L. Fox is the Microbe Current Topics and Features Editor.

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