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The pneumococcus can metabolize a range of carbohydrates that feed into glycolysis ending in pyruvate, which is catabolized by several enzymes. We investigated how the pneumococcus utilizes these enzymes to metabolize different carbohydrates and how this impacts survival in the host. Loss of <jats:italic>ldh<\/jats:italic> decreased bacterial burden in the nasopharynx and enhanced bacteremia in mice. Loss of <jats:italic>spxB<\/jats:italic>, <jats:italic>pdhC<\/jats:italic> or <jats:italic>pfl2<\/jats:italic> decreased bacteremia and increased host survival. In glucose or galactose, loss of <jats:italic>ldh<\/jats:italic> increased capsule production, whereas loss of <jats:italic>spxB<\/jats:italic> and <jats:italic>pdhC<\/jats:italic> reduced capsule production. The <jats:italic>pfl2<\/jats:italic> mutant exhibited reduced capsule production only in galactose. In glucose, pyruvate was metabolized primarily by LDH to generate lactate and NAD<jats:sup>+<\/jats:sup> and by SpxB and PDHc to generate acetyl\u2010CoA. In galactose, pyruvate metabolism was shunted toward acetyl\u2010CoA production. The majority of acetyl\u2010CoA generated by PFL was used to regenerate NAD<jats:sup>+<\/jats:sup> with a subset used in capsule production, while the acetyl\u2010CoA generated by SpxB and PDHc was utilized primarily for capsule biosynthesis. These data suggest that the pneumococcus can alter flux of pyruvate metabolism dependent on the carbohydrate present to succeed in distinct host niches.<\/jats:p>","DOI":"10.1111\/mmi.14557","type":"journal-article","created":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T06:24:11Z","timestamp":1591251851000},"page":"536-552","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Role of the pyruvate metabolic network on carbohydrate metabolism and virulence in <i>Streptococcus pneumoniae<\/i>"],"prefix":"10.1111","volume":"114","author":[{"given":"Haley","family":"Echlin","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases St. Jude Children's Research Hospital Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases St. Jude Children's Research Hospital Memphis 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