skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria

Abstract

Extracellular electron transfer (EET) describes microbial bioelectrochemical processes in which electrons are transferred from the cytosol to the exterior of the cell1. Mineral-respiring bacteria use elaborate haem-based electron transfer mechanisms2,3,4 but the existence and mechanistic basis of other EETs remain largely unknown. Here we show that the food-borne pathogen Listeria monocytogenes uses a distinctive flavin-based EET mechanism to deliver electrons to iron or an electrode. By performing a forward genetic screen to identify L. monocytogenes mutants with diminished extracellular ferric iron reductase activity, we identified an eight-gene locus that is responsible for EET. This locus encodes a specialized NADH dehydrogenase that segregates EET from aerobic respiration by channelling electrons to a discrete membrane-localized quinone pool. Other proteins facilitate the assembly of an abundant extracellular flavoprotein that, in conjunction with free-molecule flavin shuttles, mediates electron transfer to extracellular acceptors. This system thus establishes a simple electron conduit that is compatible with the single-membrane structure of the Gram-positive cell. Activation of EET supports growth on non-fermentable carbon sources, and an EET mutant exhibited a competitive defect within the mouse gastrointestinal tract. Orthologues of the genes responsible for EET are present in hundreds of species across the Firmicutes phylum, including multiple pathogens andmore » commensal members of the intestinal microbiota, and correlate with EET activity in assayed strains. These findings suggest a greater prevalence of EET-based growth capabilities and establish a previously underappreciated relevance for electrogenic bacteria across diverse environments, including host-associated microbial communities and infectious disease.« less

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1574398
DOE Contract Number:  
AC02-05CH11231
Resource Type:
Journal Article
Journal Name:
Nature (London)
Additional Journal Information:
Journal Volume: 562; Journal Issue: 7725; Journal ID: ISSN 0028-0836
Country of Publication:
United States
Language:
English

Citation Formats

Light, Samuel H., Su, Lin, Rivera-Lugo, Rafael, Cornejo, Jose A., Louie, Alexander, Iavarone, Anthony T., Ajo-Franklin, Caroline M., and Portnoy, Daniel A. A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria. United States: N. p., 2018. Web. doi:10.1038/s41586-018-0498-z.
Light, Samuel H., Su, Lin, Rivera-Lugo, Rafael, Cornejo, Jose A., Louie, Alexander, Iavarone, Anthony T., Ajo-Franklin, Caroline M., & Portnoy, Daniel A. A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria. United States. doi:10.1038/s41586-018-0498-z.
Light, Samuel H., Su, Lin, Rivera-Lugo, Rafael, Cornejo, Jose A., Louie, Alexander, Iavarone, Anthony T., Ajo-Franklin, Caroline M., and Portnoy, Daniel A. Wed . "A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria". United States. doi:10.1038/s41586-018-0498-z.
@article{osti_1574398,
title = {A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria},
author = {Light, Samuel H. and Su, Lin and Rivera-Lugo, Rafael and Cornejo, Jose A. and Louie, Alexander and Iavarone, Anthony T. and Ajo-Franklin, Caroline M. and Portnoy, Daniel A.},
abstractNote = {Extracellular electron transfer (EET) describes microbial bioelectrochemical processes in which electrons are transferred from the cytosol to the exterior of the cell1. Mineral-respiring bacteria use elaborate haem-based electron transfer mechanisms2,3,4 but the existence and mechanistic basis of other EETs remain largely unknown. Here we show that the food-borne pathogen Listeria monocytogenes uses a distinctive flavin-based EET mechanism to deliver electrons to iron or an electrode. By performing a forward genetic screen to identify L. monocytogenes mutants with diminished extracellular ferric iron reductase activity, we identified an eight-gene locus that is responsible for EET. This locus encodes a specialized NADH dehydrogenase that segregates EET from aerobic respiration by channelling electrons to a discrete membrane-localized quinone pool. Other proteins facilitate the assembly of an abundant extracellular flavoprotein that, in conjunction with free-molecule flavin shuttles, mediates electron transfer to extracellular acceptors. This system thus establishes a simple electron conduit that is compatible with the single-membrane structure of the Gram-positive cell. Activation of EET supports growth on non-fermentable carbon sources, and an EET mutant exhibited a competitive defect within the mouse gastrointestinal tract. Orthologues of the genes responsible for EET are present in hundreds of species across the Firmicutes phylum, including multiple pathogens and commensal members of the intestinal microbiota, and correlate with EET activity in assayed strains. These findings suggest a greater prevalence of EET-based growth capabilities and establish a previously underappreciated relevance for electrogenic bacteria across diverse environments, including host-associated microbial communities and infectious disease.},
doi = {10.1038/s41586-018-0498-z},
journal = {Nature (London)},
issn = {0028-0836},
number = 7725,
volume = 562,
place = {United States},
year = {2018},
month = {9}
}

Works referenced in this record:

Extracellular electron transfer mechanisms between microorganisms and minerals
journal, August 2016

  • Shi, Liang; Dong, Hailiang; Reguera, Gemma
  • Nature Reviews Microbiology, Vol. 14, Issue 10
  • DOI: 10.1038/nrmicro.2016.93

Bacterial Manganese Reduction and Growth with Manganese Oxide as the Sole Electron Acceptor
journal, June 1988


Surface multiheme c-type cytochromes from Thermincola potens and implications for respiratory metal reduction by Gram-positive bacteria
journal, January 2012

  • Carlson, H. K.; Iavarone, A. T.; Gorur, A.
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 5
  • DOI: 10.1073/pnas.1112905109

Listeria monocytogenes — from saprophyte to intracellular pathogen
journal, August 2009

  • Freitag, Nancy E.; Port, Gary C.; Miner, Maurine D.
  • Nature Reviews Microbiology, Vol. 7, Issue 9
  • DOI: 10.1038/nrmicro2171

Reduction of ferric iron by Listeria monocytogenes and other species of Listeria
journal, May 1993

  • Deneer, Harry G.; Boychuk, Irene
  • Canadian Journal of Microbiology, Vol. 39, Issue 5
  • DOI: 10.1139/m93-068

Microbial Biofilm Voltammetry: Direct Electrochemical Characterization of Catalytic Electrode-Attached Biofilms
journal, October 2008

  • Marsili, E.; Rollefson, J. B.; Baron, D. B.
  • Applied and Environmental Microbiology, Vol. 74, Issue 23
  • DOI: 10.1128/AEM.00177-08

Disentangling the roles of free and cytochrome-bound flavins in extracellular electron transport from Shewanella oneidensis MR-1
journal, April 2016


ATP binding drives substrate capture in an ECF transporter by a release-and-catch mechanism
journal, June 2015

  • Karpowich, Nathan K.; Song, Jin Mei; Cocco, Nicolette
  • Nature Structural & Molecular Biology, Vol. 22, Issue 7
  • DOI: 10.1038/nsmb.3040

Alternative respiratory pathways of Escherichia coli: energetics and transcriptional regulation in response to electron acceptors
journal, July 1997


Alternative Pyrimidine Biosynthesis Protein ApbE Is a Flavin Transferase Catalyzing Covalent Attachment of FMN to a Threonine Residue in Bacterial Flavoproteins
journal, April 2013

  • Bertsova, Yulia V.; Fadeeva, Maria S.; Kostyrko, Vitaly A.
  • Journal of Biological Chemistry, Vol. 288, Issue 20
  • DOI: 10.1074/jbc.M113.455402

Secretion of Bacterial Lipoproteins: Through the Cytoplasmic Membrane, the Periplasm and Beyond
journal, August 2014


The Colorful World of Extracellular Electron Shuttles
journal, September 2017


Shuttling happens: soluble flavin mediators of extracellular electron transfer in Shewanella
journal, November 2011

  • Brutinel, Evan D.; Gralnick, Jeffrey A.
  • Applied Microbiology and Biotechnology, Vol. 93, Issue 1
  • DOI: 10.1007/s00253-011-3653-0

Shewanella secretes flavins that mediate extracellular electron transfer
journal, March 2008

  • Marsili, E.; Baron, D. B.; Shikhare, I. D.
  • Proceedings of the National Academy of Sciences, Vol. 105, Issue 10
  • DOI: 10.1073/pnas.0710525105

Secretion of Flavins by Shewanella Species and Their Role in Extracellular Electron Transfer
journal, December 2007

  • von Canstein, H.; Ogawa, J.; Shimizu, S.
  • Applied and Environmental Microbiology, Vol. 74, Issue 3
  • DOI: 10.1128/AEM.01387-07

Flavin Electron Shuttles Dominate Extracellular Electron Transfer by Shewanella oneidensis
journal, January 2013


Riboflavin (vitamin B-2) and health
journal, June 2003


Gut inflammation provides a respiratory electron acceptor for Salmonella
journal, September 2010

  • Winter, Sebastian E.; Thiennimitr, Parameth; Winter, Maria G.
  • Nature, Vol. 467, Issue 7314
  • DOI: 10.1038/nature09415

Host-Derived Nitrate Boosts Growth of E. coli in the Inflamed Gut
journal, February 2013


Dissimilatory Reduction of Fe(III) by Thermophilic Bacteria and Archaea in Deep Subsurface Petroleum Reservoirs of Western Siberia
journal, August 1999

  • Slobodkin, Alexander I.; Jeanthon, Christian; L'Haridon, Stéphane
  • Current Microbiology, Vol. 39, Issue 2
  • DOI: 10.1007/s002849900426

Isolation and Characterization of Metal-Reducing Thermoanaerobacter Strains from Deep Subsurface Environments of the Piceance Basin, Colorado
journal, December 2002


Fervidicola ferrireducens gen. nov., sp. nov., a thermophilic anaerobic bacterium from geothermal waters of the Great Artesian Basin, Australia
journal, April 2009

  • Ogg, C. D.; Patel, B. K. C.
  • INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY, Vol. 59, Issue 5
  • DOI: 10.1099/ijs.0.004200-0

Thermotalea metallivorans gen. nov., sp. nov., a thermophilic, anaerobic bacterium from the Great Artesian Basin of Australia aquifer
journal, April 2009

  • Ogg, C. D.; Patel, B. K. C.
  • INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY, Vol. 59, Issue 5
  • DOI: 10.1099/ijs.0.004218-0

Thermovenabulum gondwanense sp. nov., a thermophilic anaerobic Fe(III)-reducing bacterium isolated from microbial mats thriving in a Great Artesian Basin bore runoff channel
journal, August 2009

  • Ogg, C. D.; Greene, A. C.; Patel, B. K. C.
  • INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY, Vol. 60, Issue 5
  • DOI: 10.1099/ijs.0.009886-0

Fervidicella metallireducens gen. nov., sp. nov., a thermophilic, anaerobic bacterium from geothermal waters
journal, August 2009

  • Ogg, C. D.; Patel, B. K. C.
  • INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY, Vol. 60, Issue 6
  • DOI: 10.1099/ijs.0.014670-0

Flavins contained in yeast extract are exploited for anodic electron transfer by Lactococcus lactis
journal, June 2010


Riboflavin-shuttled extracellular electron transfer from Enterococcus faecalis to electrodes in microbial fuel cells
journal, November 2014

  • Zhang, Enren; Cai, Yamin; Luo, Yue
  • Canadian Journal of Microbiology, Vol. 60, Issue 11
  • DOI: 10.1139/cjm-2014-0389

Orenia metallireducens sp. nov. Strain Z6, a Novel Metal-Reducing Member of the Phylum Firmicutes from the Deep Subsurface
journal, August 2016

  • Dong, Yiran; Sanford, Robert A.; Boyanov, Maxim I.
  • Applied and Environmental Microbiology, Vol. 82, Issue 21
  • DOI: 10.1128/AEM.02382-16

Extracellular Electron Transfer Powers Enterococcus faecalis Biofilm Metabolism
journal, April 2018


Extracellular Electron Transfer by the Gram-Positive Bacterium Enterococcus faecalis
journal, July 2018


Aerobic Respiration Metabolism in Lactic Acid Bacteria and Uses in Biotechnology
journal, April 2012


Generalized transduction of serotype 1/2 and serotype 4b strains of Listeria monocytogenes
journal, January 2000


The PAMP c-di-AMP Is Essential for Listeria monocytogenes Growth in Rich but Not Minimal Media due to a Toxic Increase in (p)ppGpp
journal, June 2015

  • Whiteley, Aaron T.; Pollock, Alex J.; Portnoy, Daniel A.
  • Cell Host & Microbe, Vol. 17, Issue 6
  • DOI: 10.1016/j.chom.2015.05.006

Identification of a Peptide-Pheromone that Enhances Listeria monocytogenes Escape from Host Cell Vacuoles
journal, March 2015


Listeria monocytogenes Is Resistant to Lysozyme through the Regulation, Not the Acquisition, of Cell Wall-Modifying Enzymes
journal, August 2014

  • Burke, T. P.; Loukitcheva, A.; Zemansky, J.
  • Journal of Bacteriology, Vol. 196, Issue 21
  • DOI: 10.1128/JB.02053-14

Structure to function of an α-glucan metabolic pathway that promotes Listeria monocytogenes pathogenesis
journal, November 2016


Role of hemolysin for the intracellular growth of Listeria monocytogenes
journal, April 1988


InlA Promotes Dissemination of Listeria monocytogenes to the Mesenteric Lymph Nodes during Food Borne Infection of Mice
journal, November 2012


Commensal microbes provide first line defense against Listeria monocytogenes infection
journal, June 2017

  • Becattini, Simone; Littmann, Eric R.; Carter, Rebecca A.
  • The Journal of Experimental Medicine, Vol. 214, Issue 7
  • DOI: 10.1084/jem.20170495

Less label, more free: Approaches in label-free quantitative mass spectrometry
journal, January 2011

  • Neilson, Karlie A.; Ali, Naveid A.; Muralidharan, Sridevi
  • PROTEOMICS, Vol. 11, Issue 4
  • DOI: 10.1002/pmic.201000553

Tools for Label-free Peptide Quantification
journal, December 2012

  • Nahnsen, Sven; Bielow, Chris; Reinert, Knut
  • Molecular & Cellular Proteomics, Vol. 12, Issue 3
  • DOI: 10.1074/mcp.R112.025163

UPLC/MSE; a new approach for generating molecular fragment information for biomarker structure elucidation
journal, January 2006

  • Plumb, Robert S.; Johnson, Kelly A.; Rainville, Paul
  • Rapid Communications in Mass Spectrometry, Vol. 20, Issue 13
  • DOI: 10.1002/rcm.2550

Effects of Traveling Wave Ion Mobility Separation on Data Independent Acquisition in Proteomics Studies
journal, May 2013

  • Shliaha, Pavel V.; Bond, Nicholas J.; Gatto, Laurent
  • Journal of Proteome Research, Vol. 12, Issue 6
  • DOI: 10.1021/pr300775k

Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
journal, September 1997

  • Altschul, Stephen F.; Madden, Thomas L.; Schäffer, Alejandro A.
  • Nucleic Acids Research, Vol. 25, Issue 17, p. 3389-3402
  • DOI: 10.1093/nar/25.17.3389

Clustal W and Clustal X version 2.0
journal, September 2007


MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets
journal, March 2016

  • Kumar, Sudhir; Stecher, Glen; Tamura, Koichiro
  • Molecular Biology and Evolution, Vol. 33, Issue 7
  • DOI: 10.1093/molbev/msw054