{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T02:25:07Z","timestamp":1776997507475,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010370","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T00:00:00Z","timestamp":1648080000000}}],"reference-count":101,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Borrelia<\/jats:italic>species are amino acid auxotrophs that utilize di- and tri- peptides obtained through their oligopeptide transport system to supply amino acids for replicative growth during their enzootic cycles. However,<jats:italic>Borrelia<\/jats:italic>species from both the Lyme disease (LD) and relapsing fever (RF) groups harbor an amino acid transport and catabolism system, the Arginine Deiminase System (ADI), that could potentially augment intracellular L-arginine required for growth. RF spirochetes contain a \u201ccomplete\u201d, four gene ADI (<jats:italic>arcA<\/jats:italic>,<jats:italic>B<\/jats:italic>,<jats:italic>D<\/jats:italic>, and<jats:italic>C<\/jats:italic>) while LD spirochetes harbor<jats:italic>arcA<\/jats:italic>,<jats:italic>B<\/jats:italic>, and sometimes<jats:italic>D<\/jats:italic>but lack<jats:italic>arcC<\/jats:italic>(encoding carbamate kinase). In this study, we evaluated the role of the ADI system in bacterial survival and virulence and discovered important differences in RF and LD ADIs. Both in vitro and in a murine model of infection,<jats:italic>B<\/jats:italic>.<jats:italic>hermsii<\/jats:italic>cells significantly reduced extracellular L-arginine levels and that reduction was dependent on arginine deiminase expression. Conversely,<jats:italic>B<\/jats:italic>.<jats:italic>burgdorferi<\/jats:italic>did not reduce the concentration of L-arginine during in vitro growth experiments nor during infection of the mammalian host, suggesting a fundamental difference in the ability to directly utilize L-arginine compared to<jats:italic>B<\/jats:italic>.<jats:italic>hermsii<\/jats:italic>. Further experiments using a panel of mutants generated in both<jats:italic>B<\/jats:italic>.<jats:italic>burgdorferi<\/jats:italic>and<jats:italic>B<\/jats:italic>.<jats:italic>hermsii<\/jats:italic>, identified important differences in growth characteristics and ADI transcription and protein expression. We also found that the ADI system plays a key role in blood and spleen colonization in RF spirochetes. In this study we have identified divergent metabolic strategies in two closely related human pathogens, that ultimately impacts the host-pathogen interface during infection.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010370","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T17:53:38Z","timestamp":1647280418000},"page":"e1010370","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["The arginine deaminase system plays distinct roles in Borrelia burgdorferi and Borrelia hermsii"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5112-5095","authenticated-orcid":true,"given":"Crystal L.","family":"Richards","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra J.","family":"Raffel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9bastien","family":"Bontemps-Gallo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel P.","family":"Dulebohn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tessa C.","family":"Herbert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank C.","family":"Gherardini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"issue":"22","key":"ppat.1010370.ref001","doi-asserted-by":"crossref","first-page":"8097","DOI":"10.1128\/AEM.05316-11","article-title":"Expression of virulence factors by Staphylococcus aureus grown in serum","volume":"77","author":"Y 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