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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.01996

Polyamine Synthesis Effects Capsule Expression by Reduction of Precursors in Streptococcus pneumoniae

  • 1Mississippi State University, United States
  • 2Southeast Louisiana Veterans Health Care System, United States

Streptococcus pneumoniae (pneumococcus, Spn) colonizes the human nasopharynx asymptomatically but can cause infections such as otitis media, and invasive pneumococcal disease such as community-acquired pneumonia, meningitis and sepsis. Although the success of Spn as a pathogen can be attributed to its ability to synthesize and regulate capsular polysaccharide (CPS) for survival in the host, the mechanisms of CPS regulation are not well-described. Recent studies from our lab demonstrate that deletion of a putative polyamine biosynthesis gene (ΔcadA) in Spn TIGR4 results in the loss of the capsule. In this study, we characterized the transcriptome and metabolome of ΔcadA and identified specific mechanisms that could explain the regulatory role of polyamines in pneumococcal CPS biosynthesis. Our data indicate that impaired polyamine synthesis impacts galactose to glucose interconversion via the Leloir pathway which limits the availability of UDP-galactose, a precursor of serotype 4 CPS, and UDP-N-acetylglucosamine (UDP-GlcNAc), a nucleotide sugar precursor that is at the intersection of CPS and peptidoglycan repeat unit biosynthesis. Reduced carbon flux through glycolysis, coupled with altered fate of glycolytic intermediates further supports impaired synthesis of UDP-GlcNAc. A significant increase in the expression of transketolases indicates a potential shift in carbon flow towards the pentose phosphate pathway (PPP). Higher PPP activity could constitute oxidative stress responses in ΔcadA which warrants further investigation. The results from this study clearly demonstrate the potential of polyamine synthesis, targeted for cancer therapy in human medicine, for the development of novel prophylactic and therapeutic strategies for treating bacterial infections.

Keywords: Streptococcus pneumoniae, Polyamines, Leloir pathway, Glycolysis, Peptidoglycan, Pentose phoshate pathway, Capsule

Received: 01 Jun 2019; Accepted: 15 Aug 2019.

Copyright: © 2019 Nanduri, Ayoola, Shack, Nakamya, Thornton and Swiatlo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Bindu Nanduri, Mississippi State University, Starkville, 39762, Mississippi, United States, bnanduri@cvm.msstate.edu