Hydrogen Peroxide Production of Group A Streptococci (GAS) is emm-Type Dependent and Increased at Low Temperatures
- 38 Downloads
Group A streptococcus (GAS) is an important human pathogen whose clinical isolates differ in their ability to produce hydrogen peroxide (H2O2). H2O2 is primarily produced by the enzyme lactate oxidase (LctO), an in depth in silico research revealed that all genome-sequenced GAS possess the required gene lctO. The importance of lctO for GAS is underlined by its highly conserved catabolite control element (cre box) as well as its perfect promotor sequence in comparison to the known consensus sequences of the Gram-positive model organism Bacillus subtilis. In this study, we provide further insight in the function and regulation of lactate oxidase by analyzing a large group of clinical GAS isolates. We found that H2O2 production increased over time in the late stationary phase; after 4 days of incubation, 5.4% of the isolates showed a positive result at 37 °C, while the rate increased to 16.4% at 20 °C. This correlation between H2O2 production and low temperatures suggests additional regulatory mechanisms for lctO besides catabolite control protein A (CcpA) and indicates that lctO might play a role for GAS energy metabolism at sub-body temperatures. Furthermore, we could identify that H2O2 production was different among clinical isolates; we could correlate H2O2 production to emm-types, indicating that emm-types 6 and 75 had the highest rate of H2O2 production. The emm-type- and temperature-dependent H2O2 production of clinical GAS isolates might contribute to their different survival strategies.
Conflict of interest
The authors have no conflicts of interest to declare.
The isolates investigated within this manuscript were derived as part of routine diagnostic procedures at the University Hospital of Freiburg, Germany. The anonymized investigation of such samples and the respective clinical data review were covered by the general care contract filed between the University Hospital and the patients and/or their parents. The contract was approved by the local IRB.
- 4.Graham MR, Virtaneva K, Porcella SF, Gardner DJ, Long RD, Welty DM, Barry WT, Johnson CA, Parkins LD, Wright FA, Musser JM (2006) Analysis of the transcriptome of group A streptococcus in mouse soft tissue infection. Am J Pathol 169(3):927–942. https://doi.org/10.2353/ajpath.2006.060112 CrossRefGoogle Scholar
- 6.Shelburne SA 3rd, Keith D, Horstmann N, Sumby P, Davenport MT, Graviss EA, Brennan RG, Musser JM (2008) A direct link between carbohydrate utilization and virulence in the major human pathogen group A streptococcus. Proc Natl Acad Sci USA 105(5):1698–1703. https://doi.org/10.1073/pnas.0711767105 CrossRefGoogle Scholar
- 8.Shelburne SA, Olsen RJ, Suber B, Sahasrabhojane P, Sumby P, Brennan RG, Musser JM (2010) A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection. PLoS Pathog 6(3):e1000817. https://doi.org/10.1371/journal.ppat.1000817 CrossRefGoogle Scholar
- 9.Deutscher J, Ake FM, Derkaoui M, Zebre AC, Cao TN, Bouraoui H, Kentache T, Mokhtari A, Milohanic E, Joyet P (2014) The bacterial phosphoenolpyruvate:carbohydrate phosphotransferase system: regulation by protein phosphorylation and phosphorylation-dependent protein-protein interactions. Microbiol Mol Biol Rev 78(2):231–256. https://doi.org/10.1128/MMBR.00001-14 CrossRefGoogle Scholar
- 17.Duane PG, Rubins JB, Weisel HR, Janoff EN (1993) Identification of hydrogen peroxide as a Streptococcus pneumoniae toxin for rat alveolar epithelial cells. Infect Immun 61(10):4392–4397Google Scholar
- 20.Saito M, Ohga S, Endoh M, Nakayama H, Mizunoe Y, Hara T, Yoshida S (2001) H2O2-nonproducing Streptococcus pyogenes strains: survival in stationary phase and virulence in chronic granulomatous disease. Microbiology 147(Pt 9):2469–2477. https://doi.org/10.1099/00221287-147-9-2469 CrossRefGoogle Scholar
- 23.Rambaut A FigTree download page. http://tree.bio.ed.ac.uk/software/figtree. Accessed 9 July 2018
- 40.Kang SO, Caparon MG, Cho KH (2010) Virulence gene regulation by CvfA, a putative RNase: the CvfA-enolase complex in Streptococcus pyogenes links nutritional stress, growth-phase control, and virulence gene expression. Infect Immun 78(6):2754–2767. https://doi.org/10.1128/IAI.01370-09 CrossRefGoogle Scholar