title: Correlation of acetate catabolism and growth yield in Staphylococcus aureus: implications for host-pathogen interactions.
abstract: Recently, we reported that the prototypical Staphylococcus aureus strain RN6390 (a derivative of NCTC 8325) had significantly reduced aconitase activity relative to a diverse group of S. aureus isolates, leading to the hypothesis that strain RN6390 has impaired tricarboxylic acid (TCA) cycle-mediated acetate catabolism. Analysis of the culture supernatant from RN6390 confirmed that acetate was incompletely catabolized, suggesting that the ability to catabolize acetate can be lost by S. aureus. To test this hypothesis, we examined the carbon catabolism of the S. aureus strains whose genome sequences are publicly available. All strains catabolized glucose and excreted acetate into the culture medium. However, strains NCTC 8325 and N315 failed to catabolize acetate during the postexponential growth phase, resulting in significantly lower growth yields relative to strains that catabolized acetate. Strains NCTC 8325 and RN6390 contained an 11-bp deletion in rsbU, the gene encoding a positive regulator of the alternative sigma factor sigma(B) encoded by sigB. An isogenic derivative strain of RN6390 containing the wild-type rsbU gene had significantly increased acetate catabolism, demonstrating that sigma(B) is required for acetate catabolism. Taken together, the data suggest that naturally occurring mutations can alter the ability of S. aureus to catabolize acetate, a surprising discovery, as TCA cycle function has been demonstrated to be involved in the virulence, survival, and persistence of several pathogenic organisms. Additionally, these mutations decrease the fitness of S. aureus by reducing the number of progeny placed into subsequent generations, suggesting that in certain situations a decreased growth yield is advantageous.
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. gsomerville@niaid.nih.gov
authors.forename: Greg A
authors.initials: GA
authors.lastname: Somerville
authors.forename: Battouli
authors.initials: B
authors.lastname: Saïd-Salim
authors.forename: Jaala M
authors.initials: JM
authors.lastname: Wickman
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Raffel
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
mesh_terms: D019342:Acetic Acid / Q000378:metabolism*; D000154:Aconitate Hydratase / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics; D001427:Bacterial Toxins / Q000096:biosynthesis; D001483:Base Sequence; D005075:Biological Evolution; D002244:Carbon / Q000378:metabolism; D002952:Citric Acid Cycle; D004269:DNA, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D005838:Genotype; D006460:Hemolysin Proteins / Q000096:biosynthesis; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics; D012329:RNA, Bacterial / Q000235:genetics; D013205:Staphylococcal Protein A / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism* / Q000472:pathogenicity; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004269:DNA, Bacterial; D006460:Hemolysin Proteins; D016372:RNA, Antisense; D012329:RNA, Bacterial; C096035:RNAIII, Staphylococcus aureus; D013205:Staphylococcal Protein A; C021091:staphylococcal alpha-toxin; D002244:Carbon; D010744:Phosphoric Monoester Hydrolases; C091162:RsbU protein, Bacillus subtilis; D000154:Aconitate Hydratase; D019342:Acetic Acid