Identification of a New Lipoprotein Export Signal in Gram-Negative Bacteria

ABSTRACT Bacteria of the phylum Bacteroidetes, including commensal organisms and opportunistic pathogens, harbor abundant surface-exposed multiprotein membrane complexes (Sus-like systems) involved in carbohydrate acquisition. These complexes have been mostly linked to commensalism, and in some inst...

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Autores principales:	Frédéric Lauber, Guy Richard Cornelis, Francesco Renzi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/46cc4f69f1dd419e81ffa0ef4548ab4f
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spelling	oai:doaj.org-article:46cc4f69f1dd419e81ffa0ef4548ab4f2021-11-15T15:50:14ZIdentification of a New Lipoprotein Export Signal in Gram-Negative Bacteria10.1128/mBio.01232-162150-7511https://doaj.org/article/46cc4f69f1dd419e81ffa0ef4548ab4f2016-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01232-16https://doaj.org/toc/2150-7511ABSTRACT Bacteria of the phylum Bacteroidetes, including commensal organisms and opportunistic pathogens, harbor abundant surface-exposed multiprotein membrane complexes (Sus-like systems) involved in carbohydrate acquisition. These complexes have been mostly linked to commensalism, and in some instances, they have also been shown to play a role in pathogenesis. Sus-like systems are mainly composed of lipoproteins anchored to the outer membrane and facing the external milieu. This lipoprotein localization is uncommon in most studied Gram-negative bacteria, while it is widespread in Bacteroidetes. Little is known about how these complexes assemble and particularly about how lipoproteins reach the bacterial surface. Here, by bioinformatic analyses, we identify a lipoprotein export signal (LES) at the N termini of surface-exposed lipoproteins of the human pathogen Capnocytophaga canimorsus corresponding to K-(D/E)2 or Q-A-(D/E)2. We show that, when introduced in sialidase SiaC, an intracellular lipoprotein, this signal is sufficient to target the protein to the cell surface. Mutational analysis of the LES in this reporter system showed that the amino acid composition, position of the signal sequence, and global charge are critical for lipoprotein surface transport. These findings were further confirmed by the analysis of the LES of mucinase MucG, a naturally surface-exposed C. canimorsus lipoprotein. Furthermore, we identify a LES in Bacteroides fragilis and Flavobacterium johnsoniae surface lipoproteins that allow C. canimorsus surface protein exposure, thus suggesting that Bacteroidetes share a new bacterial lipoprotein export pathway that flips lipoproteins across the outer membrane. IMPORTANCE Bacteria of the phylum Bacteroidetes are important human commensals and pathogens. Understanding their biology is therefore a key question for human health. A main feature of these bacteria is the presence of abundant lipoproteins at their surface that play a role in nutrient acquisition. To date, the underlying mechanism of lipoprotein transport is unknown. We show for the first time that Bacteroidetes surface lipoproteins share an N-terminal signal that drives surface localization. The localization and overall negative charge of the lipoprotein export signal (LES) are crucial for its role. Overall, our findings provide the first evidence that Bacteroidetes are endowed with a new bacterial lipoprotein export pathway that flips lipoproteins across the outer membrane.Frédéric LauberGuy Richard CornelisFrancesco RenziAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 5 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Frédéric Lauber Guy Richard Cornelis Francesco Renzi Identification of a New Lipoprotein Export Signal in Gram-Negative Bacteria
description	ABSTRACT Bacteria of the phylum Bacteroidetes, including commensal organisms and opportunistic pathogens, harbor abundant surface-exposed multiprotein membrane complexes (Sus-like systems) involved in carbohydrate acquisition. These complexes have been mostly linked to commensalism, and in some instances, they have also been shown to play a role in pathogenesis. Sus-like systems are mainly composed of lipoproteins anchored to the outer membrane and facing the external milieu. This lipoprotein localization is uncommon in most studied Gram-negative bacteria, while it is widespread in Bacteroidetes. Little is known about how these complexes assemble and particularly about how lipoproteins reach the bacterial surface. Here, by bioinformatic analyses, we identify a lipoprotein export signal (LES) at the N termini of surface-exposed lipoproteins of the human pathogen Capnocytophaga canimorsus corresponding to K-(D/E)2 or Q-A-(D/E)2. We show that, when introduced in sialidase SiaC, an intracellular lipoprotein, this signal is sufficient to target the protein to the cell surface. Mutational analysis of the LES in this reporter system showed that the amino acid composition, position of the signal sequence, and global charge are critical for lipoprotein surface transport. These findings were further confirmed by the analysis of the LES of mucinase MucG, a naturally surface-exposed C. canimorsus lipoprotein. Furthermore, we identify a LES in Bacteroides fragilis and Flavobacterium johnsoniae surface lipoproteins that allow C. canimorsus surface protein exposure, thus suggesting that Bacteroidetes share a new bacterial lipoprotein export pathway that flips lipoproteins across the outer membrane. IMPORTANCE Bacteria of the phylum Bacteroidetes are important human commensals and pathogens. Understanding their biology is therefore a key question for human health. A main feature of these bacteria is the presence of abundant lipoproteins at their surface that play a role in nutrient acquisition. To date, the underlying mechanism of lipoprotein transport is unknown. We show for the first time that Bacteroidetes surface lipoproteins share an N-terminal signal that drives surface localization. The localization and overall negative charge of the lipoprotein export signal (LES) are crucial for its role. Overall, our findings provide the first evidence that Bacteroidetes are endowed with a new bacterial lipoprotein export pathway that flips lipoproteins across the outer membrane.
format	article
author	Frédéric Lauber Guy Richard Cornelis Francesco Renzi
author_facet	Frédéric Lauber Guy Richard Cornelis Francesco Renzi
author_sort	Frédéric Lauber
title	Identification of a New Lipoprotein Export Signal in Gram-Negative Bacteria
title_short	Identification of a New Lipoprotein Export Signal in Gram-Negative Bacteria
title_full	Identification of a New Lipoprotein Export Signal in Gram-Negative Bacteria
title_fullStr	Identification of a New Lipoprotein Export Signal in Gram-Negative Bacteria
title_full_unstemmed	Identification of a New Lipoprotein Export Signal in Gram-Negative Bacteria
title_sort	identification of a new lipoprotein export signal in gram-negative bacteria
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/46cc4f69f1dd419e81ffa0ef4548ab4f
work_keys_str_mv	AT fredericlauber identificationofanewlipoproteinexportsignalingramnegativebacteria AT guyrichardcornelis identificationofanewlipoproteinexportsignalingramnegativebacteria AT francescorenzi identificationofanewlipoproteinexportsignalingramnegativebacteria
_version_	1718427454776803328

Identification of a New Lipoprotein Export Signal in Gram-Negative Bacteria

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