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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Microbes and Innate Immunity
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1458435
This article is part of the Research Topic Unravelling Host-Pathogen Interactions in Bacterial Infection: Insights from Omics and Machine Learning View all articles

Single-stranded DNA oligonucleotides containing CpG motifs are nonstimulatory in vitro but offer protection in vivo against Burkholderia pseudomallei

Provisionally accepted
Andrew E. Scott Andrew E. Scott 1Tom Young Tom Young 2Joann L. Prior Joann L. Prior 1Chad W. Stratilo Chad W. Stratilo 3Leonie Unterholzner Leonie Unterholzner 2Riccardo V. D'Elia Riccardo V. D'Elia 1*
  • 1 Defence Science and Technology Laboratory, Salisbury, United Kingdom
  • 2 Department of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, England, United Kingdom
  • 3 Suffield Research Centre, Defence Research and Development Canada (DRDC), Medicine Hat, Alberta, Canada

The final, formatted version of the article will be published soon.

    Therapies that modulate and appropriately direct the immune response are promising candidates for the treatment of infectious diseases. One such candidate therapeutic is DZ13, a short synthetic singlestranded DNA molecule. This molecule has enzymatic activity and can modulate the immune response by binding to and degrading the mRNA encoding a key immuno-regulatory molecule. Originally developed and entering clinical trials as an anti-cancer agent, DZ13 has also been evaluated as a treatment for viral infections, and has been shown to provide protection against infection with influenza virus in a mouse model of infection.In this work, we evaluated whether the immuno-modulatory properties of DZ13 could provide protection against the potential biothreat pathogen Burkholderia pseudomallei which causes the neglected tropical disease melioidosis. Treatment of mice infected with B. pseudomallei demonstrated that DZ13 did indeed provide excellent protection after only two post-exposure treatments. However, our data indicated that the enzymatic activity contained in DZ13 was not required for protection, with control oligonucleotide treatments lacking activity against the target mRNA equally as protective against B. pseudomallei.We have designed new sequences to study the mechanism of protection further. These novel sequences offer enhanced protection against infection, but are not directly anti-microbial and do not appear to be stimulating the immune system via TLR9 or other key innate immune sensors, despite containing CpG motifs. The molecular mechanism of these novel sequences remains to be elucidated, but the data highlights that these oligonucleotide-sensing pathways are attractive and relevant targets to modulate during bacterial and viral infections.

    Keywords: Melioidosis, DNAzyme, CpG, anti-inflammatory, Burkholderia pseudomallei

    Received: 02 Jul 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 Scott, Young, Prior, Stratilo, Unterholzner and D'Elia. 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) or licensor 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: Riccardo V. D'Elia, Defence Science and Technology Laboratory, Salisbury, United Kingdom

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