A peptide-morpholino oligomer conjugate targeting Staphylococcus aureus gyrA mRNA improves healing in an infected mouse cutaneous wound model

Andrew J. Sawyer, Donna Wesolowski, Neeru Gandotra, Alexander Stojadinovic, Mina Izadjoo, Sidney Altman, Themis R. Kyriakides

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Management of skin wound infections presents a serious problem in the clinic, in the community, and in both civilian and military clinical treatment centers. Staphylococcus aureus is one of the most common microbial pathogens in cutaneous wounds. Peptide-morpholino oligomer (PMO) conjugates targeted to S. aureus gyrase A mRNA have shown the ability to reduce bacterial viability by direct site-specific mRNA cleavage via RNase P. As a treatment, these conjugates have the added advantages of not being susceptible to resistance due to genetic mutations and are effective against drug resistant strains. While this strategy has proven effective in liquid culture, it has yet to be evaluated in an animal model of infected surface wounds. In the present study, we combined PMO conjugates with a thermoresponsive gel delivery system to treat full-thickness mouse cutaneous wounds infected with S. aureus. Wounds treated with a single dose of PMO conjugate displayed improved healing that was associated with increased epithelialization, reduced bacterial load, and increased matrix deposition. Taken together, our findings demonstrate the efficacy and flexibility of the PMO conjugate drug delivery system and make it an attractive and novel topical antimicrobial agent.

Original languageEnglish (US)
Pages (from-to)651-655
Number of pages5
JournalInternational Journal of Pharmaceutics
Volume453
Issue number2
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

Morpholinos
Staphylococcus aureus
Messenger RNA
Skin
Peptides
Wounds and Injuries
Ribonuclease P
Microbial Viability
Bacterial Load
Wound Infection
Drug Delivery Systems
Anti-Infective Agents
Animal Models
Gels
Mutation
Therapeutics
Pharmaceutical Preparations

Keywords

  • PMOs
  • RNase P
  • Skin wounds
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

A peptide-morpholino oligomer conjugate targeting Staphylococcus aureus gyrA mRNA improves healing in an infected mouse cutaneous wound model. / Sawyer, Andrew J.; Wesolowski, Donna; Gandotra, Neeru; Stojadinovic, Alexander; Izadjoo, Mina; Altman, Sidney; Kyriakides, Themis R.

In: International Journal of Pharmaceutics, Vol. 453, No. 2, 2013, p. 651-655.

Research output: Contribution to journalArticle

Sawyer, Andrew J. ; Wesolowski, Donna ; Gandotra, Neeru ; Stojadinovic, Alexander ; Izadjoo, Mina ; Altman, Sidney ; Kyriakides, Themis R. / A peptide-morpholino oligomer conjugate targeting Staphylococcus aureus gyrA mRNA improves healing in an infected mouse cutaneous wound model. In: International Journal of Pharmaceutics. 2013 ; Vol. 453, No. 2. pp. 651-655.
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