TonB-dependent transport by the gut microbiota: novel aspects of an old problem

Bolam, David N.; Berg, Bert van den

doi:10.1016/j.sbi.2018.03.001

Cited by 53 publications

(56 citation statements)

References 49 publications

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“…TBDRs mediate substrate-specific transport across the outer membrane, utilizing energy derived from the proton motive force transmitted from the TonB−ExbB−ExbD complex (TonB complex) located in the inner membrane (TonB system) 2,3 . A number of TonB systems involved in the uptake of siderophores, vitamin B12 and saccharides have been identified 4–6 . Although there are examples where the TonB system transports certain siderophores containing aromatic groups 7,8 , its involvement in the uptake and catabolism of aromatic compounds was previously unknown.…”

Section: Introductionmentioning

confidence: 99%

A TonB-dependent receptor constitutes the outer membrane transport system for a lignin-derived aromatic compound

et al. 2019

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TonB-dependent receptors (TBDRs) mediate substrate-specific transport across the outer membrane, utilizing energy derived from the proton motive force transmitted from the TonB −ExbB−ExbD complex located in the inner membrane (TonB system). Although a number of TonB systems involved in the uptake of siderophores, vitamin B12 and saccharides have been identified, their involvement in the uptake and catabolism of aromatic compounds was previously unknown. Here, we show that the outer membrane transport of a biphenyl compound derived from lignin is mediated by the TonB system in a Gram-negative bacterium capable of degrading lignin-derived aromatic compounds, Sphingobium sp. strain SYK-6. Furthermore, we found that overexpression of the corresponding TBDR gene enhanced the uptake of this biphenyl compound, contributing to the improved rate of platform chemical production. Our results will provide an important basis for establishing engineered strains optimized for use in lignin valorisation.

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Section: Introductionmentioning

confidence: 99%

A TonB-dependent receptor constitutes the outer membrane transport system for a lignin-derived aromatic compound

et al. 2019

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“…The Ton system was first characterized for its role in the uptake of phages T1 and T5 [8] and subsequently studied for its role in iron-bound siderophore import, however, a growing number of different ligands has been identified, from individual zinc ions to polysaccharides [9][10][11][12][13][14]. Bacteriocins, which are able to kill the infected cell with very high efficiency, hijack the Ton system to mediate binding at the surface and to provide energy for their uptake across the outer membrane [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Structure and Stoichiometry of the Ton Molecular Motor

Celia

Noinaj

Buchanan

2020

IJMS

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The Ton complex is a molecular motor that uses the proton gradient at the inner membrane of Gram-negative bacteria to generate force and movement, which are transmitted to transporters at the outer membrane, allowing the entry of nutrients into the periplasmic space. Despite decades of investigation and the recent flurry of structures being reported by X-ray crystallography and cryoEM, the mode of action of the Ton molecular motor has remained elusive, and the precise stoichiometry of its subunits is still a matter of debate. This review summarizes the latest findings on the Ton system by presenting the recently reported structures and related reports on the stoichiometry of the fully assembled complex.

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“…In the consensus model of TonB-dependent transport 14 , extracellular substrate binding generates conformational changes in the plug domain of the TBDT that are transmitted to its N-terminal Ton box. This increases accessibility of the Ton box from the periplasm, allowing interaction with TonB in the inner membrane.…”

Section: Resultsmentioning

confidence: 99%

“…The rag locus was probably obtained via horizontal gene transfer of the sus operon, as it is located on a pathogenicity island of P. gingivalis 21,23,24 . In contrast to environmental and commensal Bacteroidetes that have many SusCD systems dedicated to glycan transport 14 , all P. gingivalis strains sequenced to date (57 in total) have only one ragAB operon. A single ragAB operon is also present in all strains of Porphyromonas gulae (12 in total), the pathogenic equivalent of P. gingivalis in dogs, and in some other closely related oral species of Porphyromonas .…”

Section: Discussionmentioning

confidence: 99%

Dynamic oligopeptide acquisition by the RagAB transporter fromPorphyromonas gingivalis

Madej

Jbr

Nowakowska

et al. 2019

Preprint

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38Porphyromonas gingivalis, an asaccharolytic Bacteroidetes, is a keystone pathogen in human 39 periodontitis that may also contribute to the development of other chronic inflammatory diseases, 40 such as rheumatoid arthritis, cardiovascular disease and Alzheimer's disease. P. gingivalis utilizes 41 protease-generated peptides derived from extracellular proteins for growth, but how those peptides 42 enter the cell is not clear. Here we identify RagAB as the outer membrane importer for peptides. X-43 ray crystal structures show that the transporter forms a dimeric RagA 2 B 2 complex with the RagB 44 substrate binding surface-anchored lipoprotein forming a closed lid on the TonB-dependent 45 transporter RagA. Cryo-electron microscopy structures reveal the opening of the RagB lid and thus 46 provide direct evidence for a "pedal bin" nutrient uptake mechanism. Together with mutagenesis, 47 peptide binding studies and RagAB peptidomics, our work identifies RagAB as a dynamic OM 48 oligopeptide acquisition machine with considerable substrate selectivity that is essential for the 49 efficient utilisation of proteinaceous nutrients by P. gingivalis. 50 51 Introduction 52 The Gram-negative Bacteroidetes are abundant members of the human microbiota, especially in 53 the gut. Outside the gut, Bacteroidetes often cause disease, with the best-known examples being 54 the oral Bacteroidetes Porphyromonas gingivalis and Tannerella forsythia that are part of the "red 55 complex" involved in periodontitis 1 , the most prevalent infection-driven chronic inflammation in the 56 Western world 2 . Accumulating evidence suggests a link between periodontitis and other chronic 57 inflammatory diseases, including rheumatoid arthritis, Alzheimer's disease, chronic obstructive 58 pulmonary disease and cardiovascular disease 3-7 . Given this link, and the fastidious growth 59 requirements of P. gingivalis, it is important to understand how this key pathogen thrives and 60 causes dysbiosis of the oral microbiota in the biofilm on the tooth surface below the gum line, 61 leading to inflammation and periodontal tissue destruction. 63Unlike many human gut Bacteroidetes that specialise in degrading complex host and dietary 64 glycans, P. gingivalis is asaccharolytic and exclusively utilises peptides for growth 8 . Those 65 peptides are generated by multiple proteases, including several secreted endopeptidases and 66 periplasmic di-and tri-peptidyl-peptidases 9,10 . The best-known P. gingivalis endopeptidases are the 67 gingipains, large and abundant surface-anchored cysteine proteases with cumulative trypsin-like 68 activity, which are essential for P. gingivalis virulence and growth on proteins as the sole source of 69 carbon 11 . Crucially, it is not clear how gingipain-generated peptides are taken up by P. gingivalis. A 70 role in this process has been proposed for the RagAB outer membrane (OM) protein complex 12 , 71 which consists of a TonB dependent transporter (TBDT) RagA (PG_0185) and a substrate binding72 surface lipoprotein RagB (PG_0186...

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TonB-dependent transport by the gut microbiota: novel aspects of an old problem

Cited by 53 publications

References 49 publications

A TonB-dependent receptor constitutes the outer membrane transport system for a lignin-derived aromatic compound

A TonB-dependent receptor constitutes the outer membrane transport system for a lignin-derived aromatic compound

Structure and Stoichiometry of the Ton Molecular Motor

Dynamic oligopeptide acquisition by the RagAB transporter fromPorphyromonas gingivalis

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