title: Advantage of upregulation of succinate dehydrogenase in Staphylococcus aureus biofilms.
abstract: Previous studies have demonstrated that various tricarboxylic acid (TCA) cycle genes, particularly the succinate dehydrogenase genes (sdhCAB), are upregulated in Staphylococcus aureus biofilms. To better study the role of this enzyme complex, an sdhCAB deletion mutant (Deltasdh) was constructed. Compared to the wild type (wt) the mutant was impaired in planktonic growth under aerobic conditions, excreted acetic acid could not be reused and accumulated continuously, succinate was excreted and found in the culture supernatant, and metabolome analysis with cells grown in chemically defined medium revealed reduced uptake/metabolism of some amino acids from the growth medium. Moreover, the mutant was able to counteract the steadily decreasing extracellular pH by increased urease activity. The addition of fumarate to the growth medium restored the wt phenotype. The mutant showed a small-colony variant (SCV)-like phenotype, a slight increase in resistance to various aminoglycoside antibiotics, and decreased pigmentation. The decreased growth under aerobic conditions is due to the interruption of the TCA cycle (indicated by the accumulation of succinate and acetic acid) with the consequence that many fewer reduction equivalents (NADH and FADH2) can fuel the respiratory chain. The results indicate that the TCA cycle is required for acetate and amino acid catabolism; its upregulation under biofilm conditions is advantageous under such nutrient- and oxygen-limited conditions.
authors.affiliation: Mikrobielle Genetik, Universität Tübingen, 72076 Tübingen, Germany.
authors.forename: Rosmarie
authors.initials: R
authors.lastname: Gaupp
authors.forename: Steffen
authors.initials: S
authors.lastname: Schlag
authors.forename: Manuel
authors.initials: M
authors.lastname: Liebeke
authors.forename: Michael
authors.initials: M
authors.lastname: Lalk
authors.forename: Friedrich
authors.initials: F
authors.lastname: Götz
mesh_terms: D000085:Acetates / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D005650:Fumarates / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development*; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D019802:Succinic Acid / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology; D014510:Urease / Q000235:genetics / Q000378:metabolism
chemical_list: D000085:Acetates; D001426:Bacterial Proteins; D005650:Fumarates; D019802:Succinic Acid; D013385:Succinate Dehydrogenase; D014510:Urease