Cargando…

A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism

During persistent infection, optimal expression of bacterial factors is required to match the ever-changing host environment. The gastric pathogen Helicobacter pylori has a large set of simple sequence repeats (SSR), which constitute contingency loci. Through a slipped strand mispairing mechanism, t...

Descripción completa

Detalles Bibliográficos
Autores principales: Åberg, Anna, Gideonsson, Pär, Vallström, Anna, Olofsson, Annelie, Öhman, Carina, Rakhimova, Lena, Borén, Thomas, Engstrand, Lars, Brännström, Kristoffer, Arnqvist, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081817/
https://www.ncbi.nlm.nih.gov/pubmed/24991812
http://dx.doi.org/10.1371/journal.ppat.1004234
_version_ 1782324156911583232
author Åberg, Anna
Gideonsson, Pär
Vallström, Anna
Olofsson, Annelie
Öhman, Carina
Rakhimova, Lena
Borén, Thomas
Engstrand, Lars
Brännström, Kristoffer
Arnqvist, Anna
author_facet Åberg, Anna
Gideonsson, Pär
Vallström, Anna
Olofsson, Annelie
Öhman, Carina
Rakhimova, Lena
Borén, Thomas
Engstrand, Lars
Brännström, Kristoffer
Arnqvist, Anna
author_sort Åberg, Anna
collection PubMed
description During persistent infection, optimal expression of bacterial factors is required to match the ever-changing host environment. The gastric pathogen Helicobacter pylori has a large set of simple sequence repeats (SSR), which constitute contingency loci. Through a slipped strand mispairing mechanism, the SSRs generate heterogeneous populations that facilitate adaptation. Here, we present a model that explains, in molecular terms, how an intergenically located T-tract, via slipped strand mispairing, operates with a rheostat-like function, to fine-tune activity of the promoter that drives expression of the sialic acid binding adhesin, SabA. Using T-tract variants, in an isogenic strain background, we show that the length of the T-tract generates multiphasic output from the sabA promoter. Consequently, this alters the H. pylori binding to sialyl-Lewis x receptors on gastric mucosa. Fragment length analysis of post-infection isolated clones shows that the T-tract length is a highly variable feature in H. pylori. This mirrors the host-pathogen interplay, where the bacterium generates a set of clones from which the best-fit phenotypes are selected in the host. In silico and functional in vitro analyzes revealed that the length of the T-tract affects the local DNA structure and thereby binding of the RNA polymerase, through shifting of the axial alignment between the core promoter and UP-like elements. We identified additional genes in H. pylori, with T- or A-tracts positioned similar to that of sabA, and show that variations in the tract length likewise acted as rheostats to modulate cognate promoter output. Thus, we propose that this generally applicable mechanism, mediated by promoter-proximal SSRs, provides an alternative mechanism for transcriptional regulation in bacteria, such as H. pylori, which possesses a limited repertoire of classical trans-acting regulatory factors.
format Online
Article
Text
id pubmed-4081817
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-40818172014-07-10 A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism Åberg, Anna Gideonsson, Pär Vallström, Anna Olofsson, Annelie Öhman, Carina Rakhimova, Lena Borén, Thomas Engstrand, Lars Brännström, Kristoffer Arnqvist, Anna PLoS Pathog Research Article During persistent infection, optimal expression of bacterial factors is required to match the ever-changing host environment. The gastric pathogen Helicobacter pylori has a large set of simple sequence repeats (SSR), which constitute contingency loci. Through a slipped strand mispairing mechanism, the SSRs generate heterogeneous populations that facilitate adaptation. Here, we present a model that explains, in molecular terms, how an intergenically located T-tract, via slipped strand mispairing, operates with a rheostat-like function, to fine-tune activity of the promoter that drives expression of the sialic acid binding adhesin, SabA. Using T-tract variants, in an isogenic strain background, we show that the length of the T-tract generates multiphasic output from the sabA promoter. Consequently, this alters the H. pylori binding to sialyl-Lewis x receptors on gastric mucosa. Fragment length analysis of post-infection isolated clones shows that the T-tract length is a highly variable feature in H. pylori. This mirrors the host-pathogen interplay, where the bacterium generates a set of clones from which the best-fit phenotypes are selected in the host. In silico and functional in vitro analyzes revealed that the length of the T-tract affects the local DNA structure and thereby binding of the RNA polymerase, through shifting of the axial alignment between the core promoter and UP-like elements. We identified additional genes in H. pylori, with T- or A-tracts positioned similar to that of sabA, and show that variations in the tract length likewise acted as rheostats to modulate cognate promoter output. Thus, we propose that this generally applicable mechanism, mediated by promoter-proximal SSRs, provides an alternative mechanism for transcriptional regulation in bacteria, such as H. pylori, which possesses a limited repertoire of classical trans-acting regulatory factors. Public Library of Science 2014-07-03 /pmc/articles/PMC4081817/ /pubmed/24991812 http://dx.doi.org/10.1371/journal.ppat.1004234 Text en © 2014 Åberg et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Åberg, Anna
Gideonsson, Pär
Vallström, Anna
Olofsson, Annelie
Öhman, Carina
Rakhimova, Lena
Borén, Thomas
Engstrand, Lars
Brännström, Kristoffer
Arnqvist, Anna
A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism
title A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism
title_full A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism
title_fullStr A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism
title_full_unstemmed A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism
title_short A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism
title_sort repetitive dna element regulates expression of the helicobacter pylori sialic acid binding adhesin by a rheostat-like mechanism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081817/
https://www.ncbi.nlm.nih.gov/pubmed/24991812
http://dx.doi.org/10.1371/journal.ppat.1004234
work_keys_str_mv AT aberganna arepetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT gideonssonpar arepetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT vallstromanna arepetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT olofssonannelie arepetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT ohmancarina arepetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT rakhimovalena arepetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT borenthomas arepetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT engstrandlars arepetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT brannstromkristoffer arepetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT arnqvistanna arepetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT aberganna repetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT gideonssonpar repetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT vallstromanna repetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT olofssonannelie repetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT ohmancarina repetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT rakhimovalena repetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT borenthomas repetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT engstrandlars repetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT brannstromkristoffer repetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism
AT arnqvistanna repetitivednaelementregulatesexpressionofthehelicobacterpylorisialicacidbindingadhesinbyarheostatlikemechanism