<italic toggle="yes">In Vivo</italic> Genome and Methylome Adaptation of <italic toggle="yes">cag</italic>-Negative <named-content content-type="genus-species">Helicobacter pylori</named-content> during Experimental Human Infection

ABSTRACT Multiple studies have demonstrated rapid bacterial genome evolution during chronic infection with Helicobacter pylori. In contrast, little was known about genetic changes during the first stages of infection, when selective pressure is likely to be highest. Using single-molecule, real-time...

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Autores principales:	Iratxe Estibariz, Florent Ailloud, Sabrina Woltemate, Boyke Bunk, Cathrin Spröer, Jörg Overmann, Toni Aebischer, Thomas F. Meyer, Christine Josenhans, Sebastian Suerbaum
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	DNA methylation Helicobacter pylori adaptive mutations genome analysis SMRT sequencing PacBio Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bfe6793abcf147fc94bb9eb3f15a1f29
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spelling	oai:doaj.org-article:bfe6793abcf147fc94bb9eb3f15a1f292021-11-15T15:56:44Z<italic toggle="yes">In Vivo</italic> Genome and Methylome Adaptation of <italic toggle="yes">cag</italic>-Negative <named-content content-type="genus-species">Helicobacter pylori</named-content> during Experimental Human Infection10.1128/mBio.01803-202150-7511https://doaj.org/article/bfe6793abcf147fc94bb9eb3f15a1f292020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01803-20https://doaj.org/toc/2150-7511ABSTRACT Multiple studies have demonstrated rapid bacterial genome evolution during chronic infection with Helicobacter pylori. In contrast, little was known about genetic changes during the first stages of infection, when selective pressure is likely to be highest. Using single-molecule, real-time (SMRT) and Illumina sequencing technologies, we analyzed genome and methylome evolution during the first 10 weeks of infection by comparing the cag pathogenicity island (cagPAI)-negative H. pylori challenge strain BCS 100 with pairs of H. pylori reisolates from gastric antrum and corpus biopsy specimens of 10 human volunteers who had been infected with this strain as part of a vaccine trial. Most genetic changes detected in the reisolates affected genes with a surface-related role or a predicted function in peptide uptake. Apart from phenotypic changes of the bacterial envelope, a duplication of the catalase gene was observed in one reisolate, which resulted in higher catalase activity and improved survival under oxidative stress conditions. The methylomes also varied in some of the reisolates, mostly by activity switching of phase-variable methyltransferase (MTase) genes. The observed in vivo mutation spectrum was remarkable for a very high proportion of nonsynonymous mutations. Although the data showed substantial within-strain genome diversity in the challenge strain, most antrum and corpus reisolates from the same volunteers were highly similar to each other, indicating that the challenge infection represents a major selective bottleneck shaping the transmitted population. Our findings suggest rapid in vivo selection of H. pylori during early-phase infection providing adaptation to different individuals by common mechanisms of genetic and epigenetic alterations. IMPORTANCE Exceptional genetic diversity and variability are hallmarks of Helicobacter pylori, but the biological role of this plasticity remains incompletely understood. Here, we had the rare opportunity to investigate the molecular evolution during the first weeks of H. pylori infection by comparing the genomes and epigenomes of H. pylori strain BCS 100 used to challenge human volunteers in a vaccine trial with those of bacteria reisolated from the volunteers 10 weeks after the challenge. The data provide molecular insights into the process of establishment of this highly versatile pathogen in 10 different human individual hosts, showing, for example, selection for changes in host-interaction molecules as well as changes in epigenetic methylation patterns. The data provide important clues to the early adaptation of H. pylori to new host niches after transmission, which we believe is vital to understand its success as a chronic pathogen and develop more efficient treatments and vaccines.Iratxe EstibarizFlorent AilloudSabrina WoltemateBoyke BunkCathrin SpröerJörg OvermannToni AebischerThomas F. MeyerChristine JosenhansSebastian SuerbaumAmerican Society for MicrobiologyarticleDNA methylationHelicobacter pyloriadaptive mutationsgenome analysisSMRT sequencingPacBioMicrobiologyQR1-502ENmBio, Vol 11, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	DNA methylation Helicobacter pylori adaptive mutations genome analysis SMRT sequencing PacBio Microbiology QR1-502
spellingShingle	DNA methylation Helicobacter pylori adaptive mutations genome analysis SMRT sequencing PacBio Microbiology QR1-502 Iratxe Estibariz Florent Ailloud Sabrina Woltemate Boyke Bunk Cathrin Spröer Jörg Overmann Toni Aebischer Thomas F. Meyer Christine Josenhans Sebastian Suerbaum <italic toggle="yes">In Vivo</italic> Genome and Methylome Adaptation of <italic toggle="yes">cag</italic>-Negative <named-content content-type="genus-species">Helicobacter pylori</named-content> during Experimental Human Infection
description	ABSTRACT Multiple studies have demonstrated rapid bacterial genome evolution during chronic infection with Helicobacter pylori. In contrast, little was known about genetic changes during the first stages of infection, when selective pressure is likely to be highest. Using single-molecule, real-time (SMRT) and Illumina sequencing technologies, we analyzed genome and methylome evolution during the first 10 weeks of infection by comparing the cag pathogenicity island (cagPAI)-negative H. pylori challenge strain BCS 100 with pairs of H. pylori reisolates from gastric antrum and corpus biopsy specimens of 10 human volunteers who had been infected with this strain as part of a vaccine trial. Most genetic changes detected in the reisolates affected genes with a surface-related role or a predicted function in peptide uptake. Apart from phenotypic changes of the bacterial envelope, a duplication of the catalase gene was observed in one reisolate, which resulted in higher catalase activity and improved survival under oxidative stress conditions. The methylomes also varied in some of the reisolates, mostly by activity switching of phase-variable methyltransferase (MTase) genes. The observed in vivo mutation spectrum was remarkable for a very high proportion of nonsynonymous mutations. Although the data showed substantial within-strain genome diversity in the challenge strain, most antrum and corpus reisolates from the same volunteers were highly similar to each other, indicating that the challenge infection represents a major selective bottleneck shaping the transmitted population. Our findings suggest rapid in vivo selection of H. pylori during early-phase infection providing adaptation to different individuals by common mechanisms of genetic and epigenetic alterations. IMPORTANCE Exceptional genetic diversity and variability are hallmarks of Helicobacter pylori, but the biological role of this plasticity remains incompletely understood. Here, we had the rare opportunity to investigate the molecular evolution during the first weeks of H. pylori infection by comparing the genomes and epigenomes of H. pylori strain BCS 100 used to challenge human volunteers in a vaccine trial with those of bacteria reisolated from the volunteers 10 weeks after the challenge. The data provide molecular insights into the process of establishment of this highly versatile pathogen in 10 different human individual hosts, showing, for example, selection for changes in host-interaction molecules as well as changes in epigenetic methylation patterns. The data provide important clues to the early adaptation of H. pylori to new host niches after transmission, which we believe is vital to understand its success as a chronic pathogen and develop more efficient treatments and vaccines.
format	article
author	Iratxe Estibariz Florent Ailloud Sabrina Woltemate Boyke Bunk Cathrin Spröer Jörg Overmann Toni Aebischer Thomas F. Meyer Christine Josenhans Sebastian Suerbaum
author_facet	Iratxe Estibariz Florent Ailloud Sabrina Woltemate Boyke Bunk Cathrin Spröer Jörg Overmann Toni Aebischer Thomas F. Meyer Christine Josenhans Sebastian Suerbaum
author_sort	Iratxe Estibariz
title	<italic toggle="yes">In Vivo</italic> Genome and Methylome Adaptation of <italic toggle="yes">cag</italic>-Negative <named-content content-type="genus-species">Helicobacter pylori</named-content> during Experimental Human Infection
title_short	<italic toggle="yes">In Vivo</italic> Genome and Methylome Adaptation of <italic toggle="yes">cag</italic>-Negative <named-content content-type="genus-species">Helicobacter pylori</named-content> during Experimental Human Infection
title_full	<italic toggle="yes">In Vivo</italic> Genome and Methylome Adaptation of <italic toggle="yes">cag</italic>-Negative <named-content content-type="genus-species">Helicobacter pylori</named-content> during Experimental Human Infection
title_fullStr	<italic toggle="yes">In Vivo</italic> Genome and Methylome Adaptation of <italic toggle="yes">cag</italic>-Negative <named-content content-type="genus-species">Helicobacter pylori</named-content> during Experimental Human Infection
title_full_unstemmed	<italic toggle="yes">In Vivo</italic> Genome and Methylome Adaptation of <italic toggle="yes">cag</italic>-Negative <named-content content-type="genus-species">Helicobacter pylori</named-content> during Experimental Human Infection
title_sort	<italic toggle="yes">in vivo</italic> genome and methylome adaptation of <italic toggle="yes">cag</italic>-negative <named-content content-type="genus-species">helicobacter pylori</named-content> during experimental human infection
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/bfe6793abcf147fc94bb9eb3f15a1f29
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<italic toggle="yes">In Vivo</italic> Genome and Methylome Adaptation of <italic toggle="yes">cag</italic>-Negative <named-content content-type="genus-species">Helicobacter pylori</named-content> during Experimental Human Infection

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