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It can utilize a limited range of compounds as primary carbon sources, including glucose, maltose, lactate, and pyruvate, which are present in varying concentrations in microenvironments relevant to meningococcal infection. Additionally, intermediates from the tricarboxylic acid cycle, such as succinate, fumarate, and malate, as well as amino acids like glutamate, are utilized as supplementary carbon sources. Notably,\n                      <jats:italic toggle=\"yes\">N. meningitidis<\/jats:italic>\n                      also possesses a functional methylcitrate cycle (MCC), which enables the assimilation of propionic acid and mitigates its toxicity. In this study, we investigated propionate toxicity and MCC functionality in wild-type\n                      <jats:italic toggle=\"yes\">N. meningitidis<\/jats:italic>\n                      strains and\n                      <jats:italic toggle=\"yes\">prpB<\/jats:italic>\n                      -,\n                      <jats:italic toggle=\"yes\">prpC<\/jats:italic>\n                      -,\n                      <jats:italic toggle=\"yes\">ackA1-<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">ackA2<\/jats:italic>\n                      -defective mutants under various growth conditions. We observed that propionate toxicity was influenced by the primary carbon source and additional factors, such as bicarbonate. Specifically,\n                      <jats:italic toggle=\"yes\">prpB<\/jats:italic>\n                      - and\n                      <jats:italic toggle=\"yes\">prpC<\/jats:italic>\n                      -defective mutants showed high sensitivity to propionate when cultured with glucose or pyruvate, but were not inhibited even by high concentrations of propionate when grown with lactate. The mechanisms underlying the conditional toxicity of propionate were further explored and discussed. Additionally, in the genome of 41 out of 128\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">meningitidis<\/jats:italic>\n                      strains, we identified a gene encoding a transporter from the 4-toluene sulfonate uptake permease family, located between\n                      <jats:italic toggle=\"yes\">prpC<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">acnD<\/jats:italic>\n                      in the MCC gene cluster. Genetic inactivation of this gene, named\n                      <jats:italic toggle=\"yes\">kbuT<\/jats:italic>\n                      , impaired the ability to take up and oxidize \u03b1-ketobutyrate, an \u03b1-keto acid abundant in host cells, which can be used as a carbon source through the MCC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Meningococci are metabolically versatile organisms, switching between intracellular and extracellular lifestyle during colonization and invasive disease. Niche switching impacts on how bacteria communicate with host to find a balance between nutrient assimilation and protection against toxicity of some metabolites. The methylcitrate pathway fulfills this function, providing a compromise between propionate assimilation and propionate detoxification, in relation to the colonized host microenvironments. In this study, we revealed an unexpected difference in the sensitivity of meningococci to propionate when grown with different carbon sources. We also characterized the function of a gene located within the prp operon that encodes a transporter of \u03b1-ketobutyrate, an \u03b1-ketoacid abundant in host cells. These results contribute to extending our understanding of the metabolic adaptation mechanisms, which are crucial for meningococcal infection and virulence within the host microenvironments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00783-25","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T12:00:31Z","timestamp":1760961631000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Propionic acid toxicity and utilization of \u03b1-ketobutyric acid in\n                    <i>Neisseria meningitidis<\/i>\n                    via the methylcitrate cycle under specific conditions"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3275-8660","authenticated-orcid":false,"given":"Adelfia","family":"Tal\u00e0","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03fc1k060","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biological and Environmental Sciences and Technologies, University of Salento","place":["Lecce, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9745-4583","authenticated-orcid":true,"given":"Matteo","family":"Calcagnile","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03fc1k060","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Experimental Medicine, University of Salento","place":["Lecce, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6102-4151","authenticated-orcid":true,"given":"Silvia Caterina","family":"Resta","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03fc1k060","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Experimental Medicine, University of Salento","place":["Lecce, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore Maurizio","family":"Tredici","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03fc1k060","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Experimental Medicine, University of Salento","place":["Lecce, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0832-5470","authenticated-orcid":false,"given":"Giuseppe Egidio","family":"De Benedetto","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03fc1k060","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Analytical and Isotopic Mass Spectrometry, Department of Cultural Heritage, University of Salento","place":["Lecce, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6232-6183","authenticated-orcid":true,"given":"Cecilia","family":"Bucci","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03fc1k060","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Experimental Medicine, University of Salento","place":["Lecce, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3768-7275","authenticated-orcid":true,"given":"Pietro","family":"Alifano","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03fc1k060","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Experimental Medicine, University of Salento","place":["Lecce, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.VMBF-0027-2015"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/mmbr.00198-22"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00114"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/81380"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.96.2.563-.1968"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.83.3.470-474.1962"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.50.1.109-115.1945"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.101.1.127-132.1970"},{"key":"e_1_3_3_10_2","first-page":"9","article-title":"Radiorespirometric studies in genus Neisseria. 3. 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