Prospecting gene therapy of implant infections

William J. Costerton, Lucio Montanaro, Naomi Balaban, Carla Renata Arciola

Research output: Contribution to journalArticle

Abstract

Infection still represents one of the most serious and ravaging complications associated with prosthetic devices. Staphylococci and enterococci, the bacteria most frequently responsible for orthopedic postsurgical and implant-related infections, express clinically relevant antibiotic resistance. The emergence of antibiotic-resistant bacteria and the slow progress in identifying new classes of antimicrobial agents have encouraged research into novel therapeutic strategies. The adoption of antisense or "antigene" molecules able to silence or knock-out bacterial genes responsible for their virulence is one possible innovative approach. Peptide nucleic acids (PNAs) are potential drug candidates for gene therapy in infections, by silencing a basic gene of bacterial growth or by tackling the antibiotic resistance or virulence factors of a pathogen. An efficacious contrast to bacterial genes should be set up in the first stages of infection in order to prevent colonization of periprosthesis tissues. Genes encoding bacterial factors for adhesion and colonization (biofilm and/or adhesins) would be the best candidates for gene therapy. But after initial enthusiasm for direct antisense knock-out or silencing of essential or virulence bacterial genes, difficulties have emerged; consequently, new approaches are now being attempted. One of these, interference with the regulating system of virulence factors, such as agr, appears particularly promising.

Original languageEnglish
Pages (from-to)689-695
Number of pages7
JournalInternational Journal of Artificial Organs
Volume32
Issue number9
Publication statusPublished - 2009

Keywords

  • Agr
  • Antibiotic resistance
  • Biofilm
  • Enterococcus faecalis
  • Gene therapy
  • Horizontal gene transfer
  • Implant infection
  • Peptide nucleic acid (PNA)
  • Pseudomonas aeruginosa
  • Quorum sensing
  • RNAIII-activating protein (RAP)
  • RNAIII-inhibiting peptide (RIP)
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Bioengineering
  • Medicine (miscellaneous)

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  • Cite this

    Costerton, W. J., Montanaro, L., Balaban, N., & Arciola, C. R. (2009). Prospecting gene therapy of implant infections. International Journal of Artificial Organs, 32(9), 689-695.