Pathogen Evolution In Vivo: Genome Dynamics of Two Isolates Obtained 9 Years Apart from a Duodenal Ulcer Patient Infected with a Single Helicobacter pylori Strain

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Abstract
The survival and microevolution of Helicobacter pylori strains in the niches of the stomach after eradication therapy have largely been unexplored. We analyzed genomic signatures for two successive isolates obtained 9 years apart from a duodenal ulcer patient who underwent eradication therapy for H. pylori. These isolates were genotyped based on 50 different parameters involving three different fingerprinting approaches and several evolutionarily significant and virulence-associated landmarks in the genome, including nine informative gene loci, the cag pathogenicity island and its right junction, members of the plasticity region cluster, and vacA and iceA alleles. Our observations reveal that the two isolates were derived from the same strain that colonized the patient for almost a decade and were almost identical. Microevolution, however, was observed in the cagA gene and its right junction, the vacA m1 allele, and a member of the plasticity region cluster (JHP926). These results suggest that H. pylori has a great ability to survive and reemerge as a microevolved strain posteradication, thereby hinting at the requirement for follow-up of patients after therapy.

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