Genetics and Physiology of Acetate Metabolism by the Pta-Ack Pathway of Streptococcus mutans

• Published in: Applied and Environmental Microbiology 2015-08, Vol.81 (15), p.5015-5025
• Main Authors: Kim, Jeong Nam, Ahn, Sang-Joon, Burne, Robert A
• Format: Article
• Language: English
• Subjects: Acetate Kinase - genetics; Acetate Kinase - metabolism; Acetates - metabolism; Acetyl Coenzyme A - metabolism; Adenosine Triphosphate - metabolism; Aerobiosis; Bacterial infections; Biofilms; Biofilms - growth & development; Gene Deletion; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genetics and Molecular Biology; Glucose - metabolism; Gram-positive bacteria; Kinases; Metabolic Networks and Pathways - genetics; Microarray Analysis; Microbiology; Molecular Sequence Data; Mutation; Organophosphates; Oxidative Stress; Pathogenesis; Phosphate Acetyltransferase - genetics; Phosphate Acetyltransferase - metabolism; Sequence Analysis, DNA; Streptococcus mutans; Streptococcus mutans - drug effects; Streptococcus mutans - genetics; Streptococcus mutans - metabolism; Streptococcus mutans - physiology
• ISSN: 0099-2240; 1098-5336; 1098-6596
• DOI: 10.1128/AEM.01160-15

In the dental caries pathogen Streptococcus mutans, phosphotransacetylase (Pta) catalyzes the conversion of acetyl coenzyme A (acetyl-CoA) to acetyl phosphate (AcP), which can be converted to acetate by acetate kinase (Ack), with the concomitant generation of ATP. A ΔackA mutant displayed enhanced accumulation of AcP under aerobic conditions, whereas little or no AcP was observed in the Δpta or Δpta ΔackA mutant. The Δpta and Δpta ΔackA mutants also had diminished ATP pools compared to the size of the ATP pool for the parental or ΔackA strain. Surprisingly, when exposed to oxidative stress, the Δpta ΔackA strain appeared to regain the capacity to produce AcP, with a concurrent increase in the size of the ATP pool compared to that for the parental strain. The ΔackA and Δpta ΔackA mutants exhibited enhanced (p)ppGpp accumulation, whereas the strain lacking Pta produced less (p)ppGpp than the wild-type strain. The ΔackA and Δpta ΔackA mutants displayed global changes in gene expression, as assessed by microarrays. All strains lacking Pta, which had defects in AcP production under aerobic conditions, were impaired in their abilities to form biofilms when glucose was the growth carbohydrate. Collectively, these data demonstrate the complex regulation of the Pta-Ack pathway and critical roles for these enzymes in processes that appear to be essential for the persistence and pathogenesis of S. mutans.