{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:07:48Z","timestamp":1788955668426,"version":"build-2803163510"},"reference-count":43,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["24K12886"],"award-info":[{"award-number":["24K12886"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JST SPRING","award":["JPMJSP2132"],"award-info":[{"award-number":["JPMJSP2132"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      D-alanine is an important amino acid for peptidoglycan biosynthesis in\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      . In addition, D-alanine is used for the modification of teichoic acids to weaken the net surface negative charge, leading to decreased susceptibility to cationic antimicrobial agents. D-alanine synthesis is dependent on only two enzymes. One is alanine racemase, encoded by the\n                      <jats:italic toggle=\"yes\">alr1<\/jats:italic>\n                      gene, which reversibly converts L-alanine and D-alanine. The other is D-amino acid transaminase, encoded by the\n                      <jats:italic toggle=\"yes\">dat<\/jats:italic>\n                      gene, which synthesizes D-amino acids from \u03b1-keto acids and other D-amino acids. In addition, the uptake of L- and D-alanine is dependent on the alanine transporter CycA. To reveal the relationship between D-alanine supply and antimicrobial susceptibility, we evaluated antimicrobial susceptibility in\n                      <jats:italic toggle=\"yes\">alr1, dat,<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">cycA<\/jats:italic>\n                      inactivation mutants. These mutants, especially the \u0394\n                      <jats:italic toggle=\"yes\">alr1<\/jats:italic>\n                      and \u0394\n                      <jats:italic toggle=\"yes\">cycA<\/jats:italic>\n                      mutants, presented increased susceptibility to \u03b2-lactams, D-cycloserine, bacitracin, lysostaphin, and cationic antimicrobial agents such as aminoglycosides, nisin A, and daptomycin. The net negative charge of the cell surface increased in the \u0394\n                      <jats:italic toggle=\"yes\">alr1<\/jats:italic>\n                      and \u0394\n                      <jats:italic toggle=\"yes\">cycA<\/jats:italic>\n                      mutants. The changes in susceptibility to antimicrobial agents and cell surface charge were restored in their gene-complemented mutants. Furthermore, in an alanine-depleted medium, the MIC for oxacillin decreased significantly, and the MIC for gentamicin also decreased slightly. Clinical MRSA strains also showed significantly increased susceptibility to oxacillin in the alanine-depleted medium. These results indicate that D-alanine deficiency leads to impaired peptidoglycan and increased net surface negative charge, resulting in increased antimicrobial susceptibility.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01936-24","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T09:39:32Z","timestamp":1749721172000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["D-alanine synthesis and exogenous alanine affect the antimicrobial susceptibility of\n                    <i>Staphylococcus aureus<\/i>"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4406-9718","authenticated-orcid":true,"given":"Yujin","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Bacteriology, Hiroshima University Graduate School of Biomedical and Health Sciences","place":["Hiroshima, Japan"]},{"name":"Department of Virology, Hiroshima University Graduate School of Biomedical and Health Sciences","place":["Hiroshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5593-5063","authenticated-orcid":true,"given":"Miki","family":"Kawada-Matsuo","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Hiroshima University Graduate School of Biomedical and Health Sciences","place":["Hiroshima, Japan"]},{"id":[{"id":"https:\/\/ror.org\/03t78wx29","id-type":"ROR","asserted-by":"publisher"}],"name":"Project Research Centre for Nosocomial Infectious Diseases, Hiroshima University","place":["Hiroshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vy Ton That","family":"Thuan","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Hiroshima University Graduate School of Biomedical and Health Sciences","place":["Hiroshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9394-6107","authenticated-orcid":true,"given":"Mi Nguyen-Tra","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Hiroshima University Graduate School of Biomedical and Health Sciences","place":["Hiroshima, Japan"]},{"id":[{"id":"https:\/\/ror.org\/03t78wx29","id-type":"ROR","asserted-by":"publisher"}],"name":"Project Research Centre for Nosocomial Infectious Diseases, Hiroshima University","place":["Hiroshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3754-1252","authenticated-orcid":true,"given":"Takemasa","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Department of Virology, Hiroshima University Graduate School of Biomedical and Health Sciences","place":["Hiroshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9094-7649","authenticated-orcid":true,"given":"Hitoshi","family":"Komatsuzawa","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Hiroshima University Graduate School of Biomedical and Health Sciences","place":["Hiroshima, Japan"]},{"id":[{"id":"https:\/\/ror.org\/03t78wx29","id-type":"ROR","asserted-by":"publisher"}],"name":"Project Research Centre for Nosocomial Infectious Diseases, Hiroshima University","place":["Hiroshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2007.00094.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1289"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-143-9-2953"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.13.8405"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2017.1417723"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","unstructured":"Panda S Jayasinghe YP Shinde DD Bueno E Stastny A Bertrand BP Chaudhari SS Kielian T Cava F Ronning DR Thomas VC. 2024. 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