Agmatine Regulates Capsule Expression in Streptococcus pneumoniae
Moses B. Ayoola1, Leslie A. Shack1, Hyungjin Eoh2, Juhyeon Lim2 and Bindu Nanduri1,3
1Department of Basic Sciences, College of Veterinary Medicine and 3 Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Mississippi State, MS
2Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA
The global burden of invasive pneumococcal disease, including pneumococcal pneumonia and sepsis, caused by Streptococcus pneumoniae (Spn), a gram-positive pathogen, remains a major health risk. The available capsule polysaccharide (CPS) based vaccines have limited serotype coverage. Emergence of drug-resistance and lack of development of novel antibiotics mandate discovery of novel therapeutics for controlling this versatile pathogen. The success of Spn as a pathogen can be attributed to its ability to regulate CPS in the host, to prevent antibody deposition and resist opsonophagocytosis. Polyamines are ubiquitous polycationic hydrocarbons, and we previously reported that impaired polyamine synthesis and transport results in attenuation in vivo. Our preliminary data indicates that polyamine mediated attenuation could be due to impaired CPS synthesis. In this study, using targeted metabolomics, we characterize the impact of the impaired cadaverine synthesis (ΔcadA/ ΔSP_0916), and polyamine transport (ΔpotABCD) on intracellular concentrations of polyamines and their precursors for synthesis, compared to the wild type Spn TIGR4. Spermidine and putrescine, putative substrates for PotABCD transporter were significantly lower in ΔpotABCD that has reduced CPS in vitro. There was no significant reduction in the levels of cadaverine in ΔcadA. However, we observed significantly lower agmatine in ΔcadA, indicating that SP_0916 is indeed an arginine decarboxylase. Furthermore, agmatine levels are lower in ΔpotABCD. Taken together, these results clearly demonstrate the critical role of agmatine in CPS synthesis in pneumococci. Further investigation of polyamine synthesis has the potential for the discovery of novel therapeutics that target these pathways.