{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T09:38:30Z","timestamp":1766137110554,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,12,8]],"date-time":"2018-12-08T00:00:00Z","timestamp":1544227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["16GRNT27260219"],"award-info":[{"award-number":["16GRNT27260219"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Listeria monocytogenes (L. monocytogenes) is a Gram-positive, enteric pathogen and the causative agent of listeriosis. During transition through the gastrointestinal tract, L. monocytogenes routinely encounters suboxic conditions. However, how the exposure to the low oxygen environment affects subsequent pathogenesis is not completely understood. Our lab previously reported that anaerobically grown L. monocytogenes exhibited an intracellular growth defect in macrophages even though the infection took place under aerobic conditions. This phenotype suggests that prior growth conditions have a prolonged effect on the outcome of subsequent intracellular infection. In this study, to further investigate the mechanisms that contribute to the compromised intracellular growth after anaerobic exposure, we hypothesized that the lack of respiratory activity under anaerobic conditions prevented anaerobically grown L. monocytogenes to establish subsequent intracellular growth under aerobic conditions. To test this hypothesis, respiratory activity in anaerobically grown L. monocytogenes was stimulated by exogenous fumarate and subsequent intracellular pathogenesis was assessed. The results showed that fumarate supplementation significantly increased the respiratory activity of anaerobically grown L. monocytogenes and rescued the subsequent intracellular growth defect, likely through promoting the production of listeriolysin O, phagosomal escape, and cell-cell spread. This study highlights the importance of respiratory activity in L. monocytogenes in modulating the outcome of subsequent intracellular infections.<\/jats:p>","DOI":"10.3390\/pathogens7040096","type":"journal-article","created":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T03:36:41Z","timestamp":1544413001000},"page":"96","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Stimulating Respiratory Activity Primes Anaerobically Grown Listeria monocytogenes for Subsequent Intracellular Infections"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1019-0429","authenticated-orcid":false,"given":"Nathan","family":"Wallace","sequence":"first","affiliation":[{"name":"Department of Biology, University of Dayton, Dayton, OH 45469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica","family":"Rinehart","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Dayton, Dayton, OH 45469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Dayton, Dayton, OH 45469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Vivant, A.-L., Garmyn, D., and Piveteau, P. (2013). Listeria monocytogenes, a down-to-earth pathogen. Front. Cell Infect. Microbiol., 3.","DOI":"10.3389\/fcimb.2013.00087"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5583","DOI":"10.1128\/AEM.01018-14","article-title":"Reservoirs of Listeria Species in Three Environmental Ecosystems","volume":"80","author":"Linke","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3201\/eid1901.120393","article-title":"Listeriosis outbreaks and associated food vehicles, United States, 1998\u20132008","volume":"19","author":"Cartwright","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_4","unstructured":"(2018, April 23). USDA ERS\u2014Cost Estimates of Foodborne Illnesses, Available online: https:\/\/www.ers.usda.gov\/data-products\/cost-estimates-of-foodborne-illnesses\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0168-1605(99)00205-6","article-title":"Survival of osmotic and acid stress by Listeria monocytogenes strains of clinical or meat origin","volume":"56","author":"Dykes","year":"2000","journal-title":"Int. J. Food Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/j.1365-2672.1990.tb02561.x","article-title":"Growth of Listeria monocytogenes at refrigeration temperatures","volume":"68","author":"Walker","year":"1990","journal-title":"J. Appl. Bacteriol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7492","DOI":"10.1128\/AEM.69.12.7492-7498.2003","article-title":"Role of the glycine betaine and carnitine transporters in adaptation of Listeria monocytogenes to chill stress in defined medium","volume":"69","author":"Angelidis","year":"2003","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s12013-013-9611-y","article-title":"Noninvasive Monitoring of Small Intestinal Oxygen in a Rat Model of Chronic Mesenteric Ischemia","volume":"67","author":"Fisher","year":"2013","journal-title":"Cell Biochem. Biophys."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1053\/j.gastro.2014.07.020","article-title":"Correlation Between Intraluminal Oxygen Gradient and Radial Partitioning of Intestinal Microbiota","volume":"147","author":"Albenberg","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5062","DOI":"10.1128\/IAI.00516-10","article-title":"Listeria monocytogenes uses Listeria adhesion protein (LAP) to promote bacterial transepithelial translocation and induces expression of LAP receptor Hsp60","volume":"78","author":"Burkholder","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.micinf.2009.05.006","article-title":"Expression of LAP, a SecA2-dependent secretory protein, is induced under anaerobic environment","volume":"11","author":"Burkholder","year":"2009","journal-title":"Microbes Infect."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wallace, N., Newton, E., Abrams, E., Zani, A., and Sun, Y. (2017). Metabolic determinants in Listeria monocytogenes anaerobic listeriolysin O production. Arch. Microbiol., 1\u201311.","DOI":"10.1007\/s00203-017-1355-4"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1128\/aem.62.1.304-307.1996","article-title":"Aerobic and anaerobic metabolism of Listeria monocytogenes in defined glucose medium","volume":"62","author":"Romick","year":"1996","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1099\/mic.0.075242-0","article-title":"Identification of genes essential for anaerobic growth of Listeria monocytogenes","volume":"160","author":"Eder","year":"2014","journal-title":"Microbiology (Read. Engl.)"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Orsi, R.H., Bergholz, T.M., Wiedmann, M., and Boor, K.J. (2015). The Listeria monocytogenes strain 10403S BioCyc database. Database, 2015.","DOI":"10.1093\/database\/bav027"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1128\/jb.107.3.770-779.1971","article-title":"Citrate cycle and related metabolism of Listeria monocytogenes","volume":"107","author":"Trivett","year":"1971","journal-title":"J. Bacteriol."},{"key":"ref_17","unstructured":"(2018, November 05). CFR\u2014Code of Federal Regulations Title 21, Available online: https:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfcfr\/CFRSearch.cfm?fr=172.350&SearchTerm=fumaric%20acid."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"370","DOI":"10.4315\/0362-028X-59.4.370","article-title":"Inhibition of Listeria monocytogenes and Escherichia coli O157:H7 on Beef by Application of Organic Acids","volume":"59","author":"Podolak","year":"1996","journal-title":"J. Food Prot."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3390\/microorganisms3010034","article-title":"Fumaric Acid and Slightly Acidic Electrolyzed Water Inactivate Gram Positive and Gram Negative Foodborne Pathogens","volume":"3","author":"Tango","year":"2015","journal-title":"Microorganisms"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1111\/tra.12397","article-title":"Human Fumarate Hydratase Is Dual Localized by an Alternative Transcription Initiation Mechanism","volume":"17","author":"Dik","year":"2016","journal-title":"Traffic"},{"key":"ref_21","unstructured":"(2018, November 05). Fumarase deficiency | Genetic and Rare Diseases Information Center (GARD)\u2014An NCATS Program, Available online: https:\/\/rarediseases.info.nih.gov\/diseases\/6476\/fumarase-deficiency."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fonc.2012.00085","article-title":"The emerging role of fumarate as an oncometabolite","volume":"2","author":"Yang","year":"2012","journal-title":"Front. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.molcel.2013.05.003","article-title":"The Proto-oncometabolite Fumarate Binds Glutathione to Amplify ROS-Dependent Signaling","volume":"51","author":"Sullivan","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.celrep.2017.09.092","article-title":"Fumarate Hydratase Loss Causes Combined Respiratory Chain Defects","volume":"21","author":"Tyrakis","year":"2017","journal-title":"Cell Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.mib.2018.10.006","article-title":"Sense and sensor ability: redox-responsive regulators in Listeria monocytogenes","volume":"47","author":"Ruhland","year":"2018","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3612","DOI":"10.1073\/pnas.1100126108","article-title":"Listeria monocytogenes transiently alters mitochondrial dynamics during infection","volume":"108","author":"Stavru","year":"2011","journal-title":"PNAS"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"17480","DOI":"10.1073\/pnas.1107857108","article-title":"Intestinal inflammation allows Salmonella to use ethanolamine to compete with the microbiota","volume":"108","author":"Thiennimitr","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/nature09415","article-title":"Gut inflammation provides a respiratory electron acceptor for Salmonella","volume":"467","author":"Winter","year":"2010","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"39742","DOI":"10.1074\/jbc.M112.394932","article-title":"Activation of cholera toxin production by anaerobic respiration of trimethylamine N-oxide in Vibrio cholerae","volume":"287","author":"Lee","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"627","DOI":"10.4014\/jmb.1512.12039","article-title":"Cholera Toxin Production Induced upon Anaerobic Respiration is Suppressed by Glucose Fermentation in Vibrio cholerae","volume":"26","author":"Oh","year":"2016","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/s41586-018-0498-z","article-title":"A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria","volume":"562","author":"Light","year":"2018","journal-title":"Nature"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/7\/4\/96\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:32:13Z","timestamp":1760196733000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/7\/4\/96"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,8]]},"references-count":31,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["pathogens7040096"],"URL":"https:\/\/doi.org\/10.3390\/pathogens7040096","relation":{},"ISSN":["2076-0817"],"issn-type":[{"type":"electronic","value":"2076-0817"}],"subject":[],"published":{"date-parts":[[2018,12,8]]}}}