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Characterisation of worldwide Helicobacter pylori strains reveals genetic conservation and essentiality of serine protease HtrA
Author(s) -
Tegtmeyer Nicole,
Moodley Yoshan,
Yamaoka Yoshio,
Pernitzsch Sandy Ramona,
Schmidt Vanessa,
Traverso Francisco Rivas,
Schmidt Thomas P.,
Rad Roland,
Yeoh Khay Guan,
Bow Ho,
Torres Javier,
Gerhard Markus,
Schneider Gisbert,
Wessler Silja,
Backert Steffen
Publication year - 2016
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13276
Subject(s) - biology , proteases , periplasmic space , helicobacter , gene , complementation , microbiology and biotechnology , serine protease , mutant , helicobacter pylori , genetics , protease , biochemistry , escherichia coli , enzyme
Summary H tr A 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 H elicobacter pylori , H tr A 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 (d RNA ‐seq) indicated that htrA is encoded in an operon with two subsequent genes, HP 1020 and HP 1021. Genetic mutagenesis and complementation studies revealed that HP 1020 and HP 1021, but not htrA , can be mutated. In addition, we demonstrate that suppression of H tr A proteolytic activity with a newly developed inhibitor is sufficient to effectively kill H . pylori , but not other bacteria. We show that H elicobacter htrA 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. H tr A can therefore be considered a promising new target for anti‐bacterial therapy.