Skip to content
DraconiticResearch
Search Sources API
186,123 studies31 sourcesUpdated 31 min ago
PreprintCC BY-NC-NDChemRxiv

An Enzyme-DNA Nanostructure with Enhanced Catalysis Accelerates MRSA Wound Healing

  • Neha Satish1,2
  • Atri Bhattacharya1,2
  • Yuanjie Sun1,2
  • Seungheon Lee1,2
  • Sara Nixon1,2
  • Rupali Chowdhry3,2
  • Devleena Samanta1,2,4,5
5 affiliations
  1. 1Department of Chemistry
  2. 2University of Texas at Austin
  3. 3Department of Public Health
  4. 4University of Texas at Austin Cancer Research Center
  5. 5Texas Materials Institute
Open at sourceDOICite

Abstract

Antibiotic-resistant wound infections are a growing clinical challenge, as bacteria evade singletarget antimicrobials and persist within protective biofilms. Antimicrobial enzymes offer a promising alternative through their catalytic generation of bactericidal species, but their therapeutic utility is limited by instability in protease-rich wound environments. Here, we demonstrate that densely grafting short DNA strands onto lactoperoxidase (LPO), an innate immune enzyme, creates an enzyme-DNA nanostructure (Nano-Lac) with enhanced proteolytic stability and catalytic activity. Whereas polymer conjugation typically compromises enzyme activity, DNA functionalization increased LPO’s catalytic turnover by >10-fold. Mechanistic studies revealed conformational changes consistent with increased active-site accessibility and reduced accumulation of an inactive oxidized intermediate under excess H2O2. These enhancements translated into broad-spectrum activity against multidrug-resistant Escherichia coli (E. coli) and methicillinresistant Staphylococcus aureus (MRSA). Nano-Lac suppressed growth, disrupted biofilms, and compromised membrane integrity, outperforming vancomycin in vitro. In a murine MRSA wound model, daily topical Nano-Lac reduced bacterial burden ~2-fold and accelerated wound closure versus native LPO and vancomycin, without histopathological signs of toxicity. Extending beyond LPO, DNA functionalization also enhanced peroxidase activity across structurally distinct heme proteins, including myoglobin, hemoglobin, and cytochrome c. These findings establish DNA grafting as a general strategy to enhance heme-protein stability, catalysis, and therapeutic function.

Related

  1. A host enzyme pseudouridylates an RNA bacteriophage genome and accelerates virus production
    J. S.-h. Kim, H. Shenasa, A. Fire +1
    bioRxivPreprintCC BY-NC-NDFull textMolecular biology & gene regulationbioRxiv
  2. Harnessing Artificial Intelligence to Understand Enzyme Catalysis and Discover New Enzymes
    Alfie-Louise R. Brownless, Shina C. L. Kamerlin
    Current opinion in structural biologyPeer-reviewedCC BYFull textMolecular biology & gene regulationPMC
  3. Multistate Enzyme Design Enables Efficient and Stereoselective Multistep Catalysis
    N. T. H. Pham, R. Guo, R. P. Garcia Jimenez +10
    bioRxivPreprintCC BY-NC-NDFull textMolecular biology & gene regulationbioRxiv
  4. Molecular Origins of Catalysis in Random Heteropolymer Enzyme Mimics through All-Atom Simulations
    Shayna L. Hilburg, Zexiang Han, Tianyi Jin +5
    The Journal of Physical Chemistry. BPeer-reviewedCC BY-NC-ND 4.0Full textMolecular biology & gene regulationPMC
  5. Evolution promotes transition-state-like conformations with enhanced basicity and electric fields in the substrate complex of a designer enzyme
    A. Lear, H. A. Bunzel, A. J. Mulholland
    bioRxivPreprintCC BYFull text1 citedMolecular biology & gene regulationbioRxiv

Cite

BibTeXRIS
BibTeX
@misc{satish2026enzymedna,
  title = {{An Enzyme-DNA Nanostructure with Enhanced Catalysis Accelerates MRSA Wound Healing}},
  author = {Neha Satish and Atri Bhattacharya and Yuanjie Sun and Seungheon Lee and Sara Nixon and Rupali Chowdhry and Devleena Samanta},
  howpublished = {ChemRxiv},
  year = {2026},
  month = oct,
  doi = {10.26434/chemrxiv.15011011/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15011011/v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - An Enzyme-DNA Nanostructure with Enhanced Catalysis Accelerates MRSA Wound Healing
AU  - Neha Satish
AU  - Atri Bhattacharya
AU  - Yuanjie Sun
AU  - Seungheon Lee
AU  - Sara Nixon
AU  - Rupali Chowdhry
AU  - Devleena Samanta
PY  - 2026
DA  - 2026/10/25
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15011011/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15011011/v1
AB  - Antibiotic-resistant wound infections are a growing clinical challenge, as bacteria evade singletarget antimicrobials and persist within protective biofilms. Antimicrobial enzymes offer a promising alternative through their catalytic generation of bactericidal species, but their therapeutic utility is limited by instability in protease-rich wound environments. Here, we demonstrate that densely grafting short DNA strands onto lactoperoxidase (LPO), an innate immune enzyme, creates an enzyme-DNA nanostructure (Nano-Lac) with enhanced proteolytic stability and catalytic activity. Whereas polymer conjugation typically compromises enzyme activity, DNA functionalization increased LPO’s catalytic turnover by >10-fold. Mechanistic studies revealed conformational changes consistent with increased active-site accessibility and reduced accumulation of an inactive oxidized intermediate under excess H2O2. These enhancements translated into broad-spectrum activity against multidrug-resistant Escherichia coli (E. coli) and methicillinresistant Staphylococcus aureus (MRSA). Nano-Lac suppressed growth, disrupted biofilms, and compromised membrane integrity, outperforming vancomycin in vitro. In a murine MRSA wound model, daily topical Nano-Lac reduced bacterial burden ~2-fold and accelerated wound closure versus native LPO and vancomycin, without histopathological signs of toxicity. Extending beyond LPO, DNA functionalization also enhanced peroxidase activity across structurally distinct heme proteins, including myoglobin, hemoglobin, and cytochrome c. These findings establish DNA grafting as a general strategy to enhance heme-protein stability, catalysis, and therapeutic function.
ER  -