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This pathogen respires aerobically if heme and quinone are available in the environment, and a functional respiratory chain is required for full virulence. Remarkably, it is shown here that the entire respiratory chain of\n            <jats:named-content content-type=\"genus-species\">S.\u00a0agalactiae<\/jats:named-content>\n            consists of only two enzymes, a type 2 NADH dehydrogenase (NDH-2) and a cytochrome\n            <jats:italic>bd<\/jats:italic>\n            oxygen reductase. There are no respiratory dehydrogenases other than NDH-2 to feed electrons into the respiratory chain, and there is only one respiratory oxygen reductase to reduce oxygen to water. Although\n            <jats:named-content content-type=\"genus-species\">S.\u00a0agalactiae<\/jats:named-content>\n            grows well in\n            <jats:italic>vitro<\/jats:italic>\n            by fermentative metabolism, it is shown here that the absence of NDH-2 results in attenuated virulence, as observed by reduced colonization in heart and kidney in a mouse model of systemic infection. The lack of NDH-2 in mammalian mitochondria and its important role for virulence suggest this enzyme may be a potential drug target. For this reason, in this study,\n            <jats:named-content content-type=\"genus-species\">S.\u00a0agalactiae<\/jats:named-content>\n            NDH-2 was purified and biochemically characterized, and the isolated enzyme was used to screen for inhibitors from libraries of FDA-approved drugs. Zafirlukast was identified to successfully inhibit both NDH-2 activity and aerobic respiration in intact cells. This compound may be useful as a laboratory tool to inhibit respiration in\n            <jats:named-content content-type=\"genus-species\">S.\u00a0agalactiae<\/jats:named-content>\n            and, since it has few side effects, it might be considered a lead compound for therapeutics development.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:named-content content-type=\"genus-species\">S.\u00a0agalactiae<\/jats:named-content>\n            is part of the human intestinal microbiota and is present in the vagina of ~30% of healthy women. Although a commensal, it is also the leading cause of septicemia and meningitis in neonates and immunocompromised adults. This organism can aerobically respire, but only using external sources of heme and quinone, required to have a functional electron transport chain. Although bacteria usually have a branched respiratory chain with multiple dehydrogenases and terminal oxygen reductases, here we establish that\n            <jats:named-content content-type=\"genus-species\">S.\u00a0agalactiae<\/jats:named-content>\n            utilizes only one type 2 NADH dehydrogenase (NDH-2) and one cytochrome\n            <jats:italic>bd<\/jats:italic>\n            oxygen reductase to perform respiration. NADH-dependent respiration plays a critical role in the pathogen in maintaining NADH\/NAD\n            <jats:sup>+<\/jats:sup>\n            redox balance in the cell, optimizing ATP production, and tolerating oxygen. In summary, we demonstrate the essential role of NDH-2 in respiration and its contribution to\n            <jats:named-content content-type=\"genus-species\">S.\u00a0agalactiae<\/jats:named-content>\n            virulence and propose it as a potential drug target.\n          <\/jats:p>","DOI":"10.1128\/mbio.01034-18","type":"journal-article","created":{"date-parts":[[2018,7,9]],"date-time":"2018-07-09T10:44:50Z","timestamp":1531133090000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Type 2 NADH Dehydrogenase Is the Only Point of Entry for Electrons into the Streptococcus agalactiae Respiratory Chain and Is a Potential Drug Target"],"prefix":"10.1128","volume":"9","author":[{"given":"Andrea M.","family":"Lencina","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Illinois, Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Franza","sequence":"additional","affiliation":[{"name":"Micalis Institute, INRA, AgroParisTech, Universit\u00e9 Paris-Saclay, Jouy-en-Josas, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"School of Medical Sciences and Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9638-8091","authenticated-orcid":false,"given":"Glen C.","family":"Ulett","sequence":"additional","affiliation":[{"name":"School of Medical Sciences and Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak S.","family":"Ipe","sequence":"additional","affiliation":[{"name":"School of Medical Sciences and Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9061-7316","authenticated-orcid":false,"given":"Philippe","family":"Gaudu","sequence":"additional","affiliation":[{"name":"Micalis Institute, INRA, AgroParisTech, Universit\u00e9 Paris-Saclay, Jouy-en-Josas, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3805-6945","authenticated-orcid":false,"given":"Robert B.","family":"Gennis","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Illinois, Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5514-2298","authenticated-orcid":false,"given":"Lici A.","family":"Schurig-Briccio","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Illinois, Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"411","volume-title":"Remington and Klein\u2019s infectious disease of the fetus and newborn infant","author":"Edwards MS","year":"2016","unstructured":"Edwards MS, Baker CJ. 2016. 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