Regulating the intersection of metabolism and pathogenesis in gram-positive bacteria

Anthony R. Richardson, Greg A. Somerville, Abraham L. Sonenshein

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Scopus citations


For prototrophic bacteria, central metabolism (i.e., glycolysis, the pentose phosphate pathway, and the Krebs cycle) supplies the 13 biosynthetic intermediates necessary to synthesize all biomolecules (Fig. 1). Gram-positive bacteria (i.e., Actinobacteria and Firmicutes) exhibit a diverse collection of central metabolic capabilities that have been shaped by reductive evolution. Some Gram-positive bacteria (e.g., Bacillus anthracis and Staphylococcus aureus) have complete central metabolic pathways, but others (e.g., Streptococcus pyogenes and Enterococcus faecium) have Krebs cycle deficiencies, and some have multiple central metabolism deficiencies (e.g., Mycoplasma genitalium and Ureaplasma parvum). These differences in central metabolic capabilities are also reflected in the bacteria's ability to persist away from a host organism; specifically, the more metabolically impaired the bacterium, the more dependent it is on its host. In essence, hosts serve as a reservoir for metabolites that overcome deficiencies in central and intermediary metabolism. Metabolic deficiencies are not created by only reductive evolution; they are also created when bacteria encounter stressful environments (e.g., iron limitation or a host immune response) that alter carbon flux (1, 2). These changes in flux alter the metabolome, which can modulate the activity of metabolite-responsive global regulators such as CodY, CcpA, Rex, and RpiR. In the first portion of this chapter, we discuss how genetic, environmental, and nutritional conditions alter the metabolome, primarily central metabolism, and in the second part, how these metabolic changes influence the activity of metabolite-responsive regulators. Finally, we discuss how metabolism and metabolite-responsive global regulators influence the outcomes of host-pathogen interactions. This review references only those manuscripts published through December 2013.

Original languageEnglish (US)
Title of host publicationMetabolism and Bacterial Pathogenesis
Number of pages37
ISBN (Electronic)9781683670926
ISBN (Print)9781555818869
StatePublished - Aug 4 2015


  • Global regulator
  • Glycolysis
  • Gram-positive bacteria
  • Metabolic changes
  • Metabolite-responsive regulator
  • Virulence gene

ASJC Scopus subject areas

  • Immunology and Microbiology(all)


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