Please use this identifier to cite or link to this item: https://doi.org/10.1111/mmi.13276
Title: Characterisation of worldwide Helicobacter pylori strains reveals genetic conservation and essentiality of serine protease HtrA
Authors: Tegtmeyer, N
Moodley, Y
Yamaoka, Y
Pernitzsch, S.R
Schmidt, V
Traverso, F.R
Schmidt, T.P
Rad, R
Yeoh, K.G 
Bow, H 
Torres, J
Gerhard, M
Schneider, G
Wessler, S
Backert, S
Keywords: HtrA protein
oligomer
serine proteinase
unclassified drug
uvomorulin
bacterial protein
cadherin
serine proteinase
Article
bacterium isolate
cell function
controlled study
DNA flanking region
extracellular space
gene expression regulation
gene inactivation
gene repression
gene structure
genetic conservation
genetic screening
genetic variability
Helicobacter infection
Helicobacter pylori
htrA gene
human
human tissue
intracellular space
major clinical study
mutagenesis
nonhuman
operon
priority journal
protein cleavage
protein degradation
RNA sequence
sequence analysis
stomach biopsy
transcription regulation
bacterial gene
enzymology
essential gene
genetic variation
genetics
Helicobacter pylori
metabolism
molecular evolution
molecular genetics
nucleotide sequence
periplasm
Bacterial Proteins
Base Sequence
Cadherins
Evolution, Molecular
Gene Expression Regulation, Bacterial
Gene Expression Regulation, Enzymologic
Gene Knockout Techniques
Genes, Bacterial
Genes, Essential
Genetic Variation
Helicobacter pylori
Humans
Molecular Sequence Data
Operon
Periplasm
Sequence Analysis, RNA
Serine Endopeptidases
Issue Date: 2016
Publisher: Blackwell Publishing Ltd
Citation: Tegtmeyer, N, Moodley, Y, Yamaoka, Y, Pernitzsch, S.R, Schmidt, V, Traverso, F.R, Schmidt, T.P, Rad, R, Yeoh, K.G, Bow, H, Torres, J, Gerhard, M, Schneider, G, Wessler, S, Backert, S (2016). Characterisation of worldwide Helicobacter pylori strains reveals genetic conservation and essentiality of serine protease HtrA. Molecular Microbiology 99 (5) : 925-944. ScholarBank@NUS Repository. https://doi.org/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. © 2016 John Wiley & Sons Ltd.
Source Title: Molecular Microbiology
URI: https://scholarbank.nus.edu.sg/handle/10635/175262
ISSN: 0950-382X
DOI: 10.1111/mmi.13276
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