Correlation of Acetate Catabolism and Growth Yield inStaphylococcus 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 B encoded by sigB. An isogenic derivative strain of RN6390 containing the wild-type rsbU gene had significantly increased acetate catabolism, demonstrating that 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.The tricarboxylic acid (TCA) cycle is an essential source of energy and biosynthetic intermediates for many organisms. Pathogenic organisms can be divided into three categories based on the TCA cycle. Those in the first group do not possess a TCA cycle and have become dependent upon the host to provide amino acids or intermediates for biosynthesis (e.g., Borrelia burgdorferi and Streptococcus pyogenes). Those in the second group have an incomplete TCA cycle and are auxotrophic for some amino acids (e.g., Yersinia pestis and Haemophilus influenzae). Lastly, the third group is characterized as having a complete TCA cycle (e.g., Pseudomonas aeruginosa and Staphylococcus aureus) but, depending upon other metabolic limitations, can be auxotrophic for certain amino acids. The relative independence of the latter two groups of pathogens on the host for amino acids suggests that the TCA cycle may perform important functions in these organisms during pathogenesis. This supposition is supported by extensive experimental data demonstrating that TCA cycle function is involved in virulence, survival, and persistence (11,20,34,36,51,53).Transcriptional regulation of TCA cycle genes is primarily dependent on the presence of oxygen and the carbon source (10,21,22,54,55). In gram-negative bacteria, TCA cycle activity is g...

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At the Crossroads of Bacterial Metabolism and Virulence Factor Synthesis in Staphylococci

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