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Jun 16, 2014

H. pylori Bacteria Frantically Mutate to Establish Infection

H. pylori Bacteria Frantically Mutate to Establish Infection

Electron micrograph of the stomach bacteria Helicobactor pylori. [Yutaka Tsutsumi, Fujita Health University School of Medicine]

  • A burst of rapid evolution allows Helicobacter pylori, the bacterium that causes ulcers in humans, to evade the immune system during the early, acute phase of infection. This finding complements earlier work that quantified how quickly H. pylori mutations accumulate during chronic infection. During the acute phase, mutational rates are 30 to 50 times greater than during the chronic phase.

    The burst in mutations was discovered by researchers at Penn State, the University of Western Australia, and the University of California, Davis. These researchers showed, for the first time and in real time, the interplay between the human immune system and invading bacteria that allows the bacteria to counter the immune system by quickly evolving. The researchers published their results June 13 in Nature Communications, in an article entitled “A mutation burst during the acute phase of Helicobacter pylori infection in humans and rhesus macaques.”

    To trace H. pylori infections in human patients, the researchers used a next-generation sequencing approach. As the researchers indicated in their article, they analyzed “the rate and pattern of genome evolution in H. pylori from the genomes of two input strains isolated from human volunteers with asymptomatic infection, and the genomes of two output strains collected 20 and 44 days after re-infection.”

    They also conducted a parallel experiment in a rhesus monkey, analyzing “genome evolution in bacteria from the genome sequences of input and output strains sequentially taken after experimental infection of a rhesus macaque.” They collected samples of the bacteria from the monkey for genome sequencing at one week, one month, two months, and six months after initial infection.

    In the monkey, the scientists were able to directly compare the rate of DNA changes in the bacterial genome between the acute and chronic stages. Although mutations continued to accumulate in the bacterial genome during the chronic phase, the rate of substitutions dropped considerably after the initial four-week period.

    “We were blown away by the very high mutation rate that we found during the initial phase of infection," said Bodo Linz, Ph.D., research associate at Penn State and lead author of the paper. Patients infected with H. pylori, experience an initial, acute phase of infection during which symptoms are most severe and the immune response is strongest.

    An infection with H. pylori triggers an immune response that involves the release of reactive oxygen and nitrogen molecules that are known to induce mutations in the DNA sequence and to cause chromosomes to break apart and recombine. Previous studies had shown that the H. pylori genome is forgiving of this kind of abuse.

    “Strains of the bacterium isolated from different human hosts vary immensely, both in DNA sequence and in gene content,” said Stephan Schuster, Ph.D., a professor of biochemistry and molecular biology at Penn State. “There are about 1,100 core genes that individual strains of H. pylori share, but another four to five hundred genes vary between strains.”

    "The intense selective pressure on the bacteria to survive the immune response, coupled with increased mutation rates, produces the incredibly fast rate of genomic change that we discovered in this study,” added Dr. Linz. “Mutations occur randomly throughout the genome, but because they help the bacteria avoid elimination by the immune system, changes in outer-membrane proteins appear much more often than would be expected by chance in the surviving bacteria.”

    Whether bacteria other than H. pylori undergo a similar burst of accelerated evolution immediately after infection is not yet known, but the team plans to investigate other common human pathogens in future research.


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