Lipoprotein Processing and Sorting in <named-content content-type="genus-species">Helicobacter pylori</named-content>

ABSTRACT Our current understanding of lipoprotein synthesis and localization in Gram-negative bacteria is based primarily on studies of Escherichia coli. Newly synthesized E. coli prolipoproteins undergo posttranslational modifications catalyzed by three essential enzymes (Lgt, LspA, and Lnt). The m...

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Autores principales:	Mark S. McClain, Bradley J. Voss, Timothy L. Cover
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Toll-like receptor 2 Helicobacter pylori lipoproteins posttranslational protein modification type IV secretion systems Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6ebec5b28d944ceb84558e28b4a91e4a
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spelling	oai:doaj.org-article:6ebec5b28d944ceb84558e28b4a91e4a2021-11-15T15:56:47ZLipoprotein Processing and Sorting in <named-content content-type="genus-species">Helicobacter pylori</named-content>10.1128/mBio.00911-202150-7511https://doaj.org/article/6ebec5b28d944ceb84558e28b4a91e4a2020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00911-20https://doaj.org/toc/2150-7511ABSTRACT Our current understanding of lipoprotein synthesis and localization in Gram-negative bacteria is based primarily on studies of Escherichia coli. Newly synthesized E. coli prolipoproteins undergo posttranslational modifications catalyzed by three essential enzymes (Lgt, LspA, and Lnt). The mature lipoproteins are then sorted to the inner or outer membrane via the Lol system (LolABCDE). Recent studies suggested that this paradigm may not be universally applicable among different classes of proteobacteria. In this study, we conducted a systematic analysis of lipoprotein processing and sorting in Helicobacter pylori, a member of the Epsilonproteobacteria that colonizes the human stomach. We show that H. pylori lgt, lspA, and lnt homologs can complement conditionally lethal E. coli mutant strains in which expression of these genes is conditionally regulated. Mutagenesis studies and analyses of conditionally lethal H. pylori mutant strains indicate that lgt and lspA are essential for H. pylori growth but lnt is dispensable. H. pylori lolA and the single lolC (or lolE) homolog are also essential genes. We then explored the role of lipoproteins in H. pylori Cag type IV secretion system (Cag T4SS) activity. Comparative analysis of the putative VirB7 homolog CagT in wild-type and lnt mutant H. pylori strains indicates that CagT undergoes amino-terminal modifications consistent with lipidation, and we show that CagT lipidation is essential for CagT stability and Cag T4SS function. This work demonstrates that lipoprotein synthesis and localization in H. pylori diverge from the canonical pathways and that lipidation of a T4SS component is necessary for H. pylori Cag T4SS activity. IMPORTANCE Bacterial lipoproteins have diverse roles in multiple aspects of bacterial physiology, antimicrobial resistance, and pathogenesis. Dedicated pathways direct the posttranslational lipidation and localization of lipoproteins, but there is considerable variation in these pathways among the proteobacteria. In this study, we characterized the proteins responsible for lipoprotein synthesis and localization in Helicobacter pylori, a member of the Epsilonproteobacteria that contributes to stomach cancer pathogenesis. We also provide evidence suggesting that lipidation of CagT, a component of the H. pylori Cag T4SS, is required for delivery of the H. pylori CagA oncoprotein into human gastric cells. Overall, these results constitute the first systematic analysis of H. pylori lipoprotein production and localization pathways and reveal how these processes in H. pylori differ from corresponding pathways in model proteobacteria.Mark S. McClainBradley J. VossTimothy L. CoverAmerican Society for MicrobiologyarticleToll-like receptor 2Helicobacter pylorilipoproteinsposttranslational protein modificationtype IV secretion systemsMicrobiologyQR1-502ENmBio, Vol 11, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Toll-like receptor 2 Helicobacter pylori lipoproteins posttranslational protein modification type IV secretion systems Microbiology QR1-502
spellingShingle	Toll-like receptor 2 Helicobacter pylori lipoproteins posttranslational protein modification type IV secretion systems Microbiology QR1-502 Mark S. McClain Bradley J. Voss Timothy L. Cover Lipoprotein Processing and Sorting in <named-content content-type="genus-species">Helicobacter pylori</named-content>
description	ABSTRACT Our current understanding of lipoprotein synthesis and localization in Gram-negative bacteria is based primarily on studies of Escherichia coli. Newly synthesized E. coli prolipoproteins undergo posttranslational modifications catalyzed by three essential enzymes (Lgt, LspA, and Lnt). The mature lipoproteins are then sorted to the inner or outer membrane via the Lol system (LolABCDE). Recent studies suggested that this paradigm may not be universally applicable among different classes of proteobacteria. In this study, we conducted a systematic analysis of lipoprotein processing and sorting in Helicobacter pylori, a member of the Epsilonproteobacteria that colonizes the human stomach. We show that H. pylori lgt, lspA, and lnt homologs can complement conditionally lethal E. coli mutant strains in which expression of these genes is conditionally regulated. Mutagenesis studies and analyses of conditionally lethal H. pylori mutant strains indicate that lgt and lspA are essential for H. pylori growth but lnt is dispensable. H. pylori lolA and the single lolC (or lolE) homolog are also essential genes. We then explored the role of lipoproteins in H. pylori Cag type IV secretion system (Cag T4SS) activity. Comparative analysis of the putative VirB7 homolog CagT in wild-type and lnt mutant H. pylori strains indicates that CagT undergoes amino-terminal modifications consistent with lipidation, and we show that CagT lipidation is essential for CagT stability and Cag T4SS function. This work demonstrates that lipoprotein synthesis and localization in H. pylori diverge from the canonical pathways and that lipidation of a T4SS component is necessary for H. pylori Cag T4SS activity. IMPORTANCE Bacterial lipoproteins have diverse roles in multiple aspects of bacterial physiology, antimicrobial resistance, and pathogenesis. Dedicated pathways direct the posttranslational lipidation and localization of lipoproteins, but there is considerable variation in these pathways among the proteobacteria. In this study, we characterized the proteins responsible for lipoprotein synthesis and localization in Helicobacter pylori, a member of the Epsilonproteobacteria that contributes to stomach cancer pathogenesis. We also provide evidence suggesting that lipidation of CagT, a component of the H. pylori Cag T4SS, is required for delivery of the H. pylori CagA oncoprotein into human gastric cells. Overall, these results constitute the first systematic analysis of H. pylori lipoprotein production and localization pathways and reveal how these processes in H. pylori differ from corresponding pathways in model proteobacteria.
format	article
author	Mark S. McClain Bradley J. Voss Timothy L. Cover
author_facet	Mark S. McClain Bradley J. Voss Timothy L. Cover
author_sort	Mark S. McClain
title	Lipoprotein Processing and Sorting in <named-content content-type="genus-species">Helicobacter pylori</named-content>
title_short	Lipoprotein Processing and Sorting in <named-content content-type="genus-species">Helicobacter pylori</named-content>
title_full	Lipoprotein Processing and Sorting in <named-content content-type="genus-species">Helicobacter pylori</named-content>
title_fullStr	Lipoprotein Processing and Sorting in <named-content content-type="genus-species">Helicobacter pylori</named-content>
title_full_unstemmed	Lipoprotein Processing and Sorting in <named-content content-type="genus-species">Helicobacter pylori</named-content>
title_sort	lipoprotein processing and sorting in <named-content content-type="genus-species">helicobacter pylori</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/6ebec5b28d944ceb84558e28b4a91e4a
work_keys_str_mv	AT marksmcclain lipoproteinprocessingandsortinginnamedcontentcontenttypegenusspecieshelicobacterpylorinamedcontent AT bradleyjvoss lipoproteinprocessingandsortinginnamedcontentcontenttypegenusspecieshelicobacterpylorinamedcontent AT timothylcover lipoproteinprocessingandsortinginnamedcontentcontenttypegenusspecieshelicobacterpylorinamedcontent
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Lipoprotein Processing and Sorting in <named-content content-type="genus-species">Helicobacter pylori</named-content>

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