Characterisation of worldwide Helicobacter pylori strains reveals genetic conservation and essentiality of serine protease HtrA

Tegtmeyer N, Moodley Y, Yamaoka Y, Pernitzsch SR, Schmidt V, Traverso FR, Schmidt TP, Rad R, Yeoh KG, Bow H, Torres J, Gerhard M, Schneider G, Wessler S, Backert S (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Molecular Microbiology Wiley-Blackwell

Book Volume: 99

Pages Range: 925-944

Journal Issue: 5

DOI: 10.1111/mmi.13276

Abstract

HtrA proteases and chaperones exhibit important roles in periplasmic protein quality control and stress responses. The genetic inactivation of htrA has been described for many bacterial pathogens. However, in some cases such as the gastric pathogen Helicobacter pylori, HtrA is secreted where it cleaves the tumour-suppressor E-cadherin interfering with gastric disease development, but the generation of htrA mutants is still lacking. Here, we show that the htrA gene locus is highly conserved in worldwide strains. HtrA presence was confirmed in 992 H.pylori isolates in gastric biopsy material from infected patients. Differential RNA-sequencing (dRNA-seq) indicated that htrA is encoded in an operon with two subsequent genes, HP1020 and HP1021. Genetic mutagenesis and complementation studies revealed that HP1020 and HP1021, but not htrA, can be mutated. In addition, we demonstrate that suppression of HtrA proteolytic activity with a newly developed inhibitor is sufficient to effectively kill H.pylori, but not other bacteria. We show that HelicobacterhtrA is an essential bifunctional gene with crucial intracellular and extracellular functions. Thus, we describe here the first microbe in which htrA is an indispensable gene, a situation unique in the bacterial kingdom. HtrA can therefore be considered a promising new target for anti-bacterial therapy.

Authors with CRIS profile

Nicole Tegtmeyer-Backert Lehrstuhl für Mikrobiologie Vanessa Schmidt Lehrstuhl für Mikrobiologie Steffen Backert Lehrstuhl für Mikrobiologie

Involved external institutions

University of Venda ZA South Africa (ZA) Michael E. DeBakey VA Medical Center US United States (USA) (US) Julius-Maximilians-Universität Würzburg DE Germany (DE) Otto-von-Guericke-Universität Magdeburg DE Germany (DE) Universität Salzburg (Paris Lodron Universität Salzburg) AT Austria (AT) Technische Universität München (TUM) DE Germany (DE) National University of Singapore (NUS) SG Singapore (SG) Instituto Mexicano del Seguro Social MX Mexico (MX) Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich CH Switzerland (CH)

How to cite

APA:

Tegtmeyer, N., Moodley, Y., Yamaoka, Y., Pernitzsch, S.R., Schmidt, V., Traverso, F.R.,... Backert, S. (2016). Characterisation of worldwide Helicobacter pylori strains reveals genetic conservation and essentiality of serine protease HtrA. Molecular Microbiology, 99(5), 925-944. https://doi.org/10.1111/mmi.13276

MLA:

Tegtmeyer, Nicole, et al. "Characterisation of worldwide Helicobacter pylori strains reveals genetic conservation and essentiality of serine protease HtrA." Molecular Microbiology 99.5 (2016): 925-944.

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