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New Sequencers May Help Unmask Bacterial Plasticity and Shed Light on Antimicrobial Resistance

NEW YORK, Jan. 12 (GenomeWeb News) - Can next-generation sequencers have an impact on molecular epidemiology?


Garth Ehrlich, executive director of the Center for Genomic Sciences at Allegheny-Singer Research Institute, thinks so. Ehrlich is interested in the plasticity of bacterial genomes and has been using a next-generation instrument to sequence bacterial strains in order to shed light on their transformability.

Though scientists have known for some time that some bacteria are transformable, what they haven't known is the degree of plasticity produced through the transformation process. Learning more about this could help researchers figure out how these organisms develop resistance to antibiotics, and researchers like Ehrlich are finding that the speed of next-generation sequencers can enable them to perform these kinds of studies without breaking the bank.

"Without the ability to look at multiple whole genomes, we couldn't really be sure," Ehrlich told GenomeWeb News.


Using 454 Life Sciences' Genome Sequencer 20, Ehrlich's group has sequenced a "number of strains" of Haemophillus influenza. "An individual strain will have about 1,500-1,600 genes, but in analyzing 10 strains, we've got double that number of genes," he said. "We talk at the population level or the species level of there being a 'supragenome,' which is many times larger than the genome of any single organism."


Because bacteria group themselves into biofilms, and because rates of transformation are much higher in biofilms, it's possible that bacteria develop resistance to antimicrobials by swapping genes in these communities.


In some cases, researchers have already identified genes that cause pathogens to become resistant, but in other cases, the sequencer could be used to identify new genes that cause resistance.


Antimicrobial resistance "will be the first area where large scale ... comparative genomics using whole sequencing will be tested, since it can be done at relatively lower cost," Bill Spencer, director of worldwide system sales at 454, said.


Since the Allegheny-SingerResearchCenterpurchasedthe Genome Sequencer 20 instrument last summer, Ehrlich said his laboratory has been able to sequence a bacterial genome at around 30X coverage in a week for a cost of about $10,000 for reagents. "If you are looking at a single read, there can be base errors, but those average out because of the depth of coverage," Ehrlich said.


"It completely changes the kind of questions you can ask because, in the past, to sequence the genome of a bacterium was a major project," Ehrlich said. "Basically, the 454 gives us the same capacity as a major ... sequencing facility."


Ehrlich's investigation into bacterial plasticity could have impact on fundamental science concepts. "The way we are going to define the (bacteria) species really is going to change," he said. "We are going to define the species by a core set of genes, and then what they have beyond that core will determine what strain they are." Currently, strains are categorized by the place of origin, a place or location, but not genetic makeup.


High throughput bacteria sequencing could also affect diagnostics, because a number of pathogens can cause multiple diseases. "We want to find out if we look at enough of these from each body site, whether we can find that there are certain sets of genes that predisposed the bacteria to causing infections in particular body sites," Ehrlich said. "Instead of thinking of all Haemophilus or all pneuomoccus the same, in the future, we will develop diagnostics and be able to say we see this pattern of genes, this is one that is going to cause people pneuomonia or that one is going to cause meningitis."


Kate O'Rourke covers the next-generation genome-sequencing market for GenomeWeb News. E-mail her at [email protected].

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