Establishment of serine protease htrA mutants in Helicobacter pylori is associated with secA mutations

Anna Zawilak-Pawlik , Urszula Zarzecka , Dorota Żyła-Uklejewicz , Jakub Lach , Dominik Strapagiel , Nicole Tegtmeyer , Manja Böhm , Steffen Backert , Joanna Skórko-Glonek

Abstract

Helicobacter pylori plays an essential role in the pathogenesis of gastritis, peptic ulcer disease, and gastric cancer. The serine protease HtrA, an important secreted virulence factor, disrupts the gastric epithelium, which enables H. pylori to transmigrate across the epithelium and inject the oncogenic CagA protein into host cells. The function of periplasmic HtrA for the H. pylori cell is unknown, mainly due to unavailability of the htrA mutants. In fact, htrA has been described as an essential gene in this bacterium. We have screened 100 worldwide H. pylori isolates and show that only in the N6 strain it was possible to delete htrA or mutate the htrA gene to produce proteolytically inactive HtrA. We have sequenced the wild-type and mutant chromosomes and we found that inactivation of htrA is associated with mutations in SecA – a component of the Sec translocon apparatus used to translocate proteins from the cytoplasm into the periplasm. The cooperation of SecA and HtrA has been already suggested in Streptococcus pneumonia, in which these two proteins co-localize. Hence, our results pinpointing a potential functional relationship between HtrA and the Sec translocon in H. pylori possibly indicate for the more general mechanism responsible to maintain bacterial periplasmic homeostasis.
Author Anna Zawilak-Pawlik - [Ludwik Hirszfeld Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences]
Anna Zawilak-Pawlik,,
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, Urszula Zarzecka (FB / DB)
Urszula Zarzecka,,
- Department of Biochemistry
, Dorota Żyła-Uklejewicz - [Ludwik Hirszfeld Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences]
Dorota Żyła-Uklejewicz,,
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, Jakub Lach - [BBMRI.pl Consortium]
Jakub Lach,,
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, Dominik Strapagiel - [BBMRI.pl Consortium]
Dominik Strapagiel,,
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, Nicole Tegtmeyer - [Friedrich-Alexander-Universität Erlangen-Nürnberg]
Nicole Tegtmeyer,,
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, Manja Böhm - [Friedrich-Alexander-Universität Erlangen-Nürnberg]
Manja Böhm,,
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, Steffen Backert - [Friedrich-Alexander-Universität Erlangen-Nürnberg]
Steffen Backert,,
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, Joanna Skórko-Glonek (FB / DB)
Joanna Skórko-Glonek,,
- Department of Biochemistry
Journal seriesScientific Reports, ISSN 2045-2322, (N/A 140 pkt)
Issue year2019
Vol9
No1
Pages1-13
Publication size in sheets0.6
Article number11794
ASJC Classification1000 Multidisciplinary
DOIDOI:10.1038/s41598-019-48030-6
URL https://www.nature.com/articles/s41598-019-48030-6.pdf
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)140
Score sourcejournalList
ScoreMinisterial score = 140.0, 27-03-2020, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus Citations = 1; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 1.401; WoS Impact Factor: 2018 = 4.011 (2) - 2018=4.525 (5)
Citation count*1 (2020-03-27)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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