Antibacterial activity of a new broad-spectrum antibiotic covalently bound to titanium surfaces

• Biofilm-associated infections, particularly those caused by Staphylococcus aureus, are a major cause of implant failure. Covalent coupling of broad-spectrum antimicrobials to implants is a promising approach to reduce the risk of infections. In this study, we developed titanium substrates on which the recently discovered antibacterial agent SPI031, a N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol, was covalently linked (SPI031-Ti). We found that SPI031-Ti substrates prevent biofilm formation of S. aureus and Pseudomonas aeruginosa in vitro, as quantified by plate counting and fluorescence microscopy. To test the effectiveness of SPI031-Ti substrates in vivo, we used an adapted in vivo biomaterial-associated infection model in mice in which SPI031-Ti substrates were implanted subcutaneously and subsequently inoculated with S. aureus. Using this model, we found a significant reduction in biofilm formation (up to 98%) on SPI031-Ti substrates compared to control substrates. Finally, we demonstrated that the functionalization of the titanium surfaces with SPI031 did not influence the adhesion and proliferation of human cells important for osseointegration and bone repair. In conclusion, these data demonstrate the clinical potential of SPI031 to be used as an antibacterial coating for implants, thereby reducing the incidence of implant-associated infections.

Nyckelord

biofilm

Pseudomonas aeruginosa

SPI031

Staphylococcus aureus

titanium

3

6 dihalogenocarbazol 1 ( sec butylamino) 3 ( 3

6 dichloro 9h carbazol 9 yl)propan 2 ol

antibiotic agent

biomaterial

carbazole derivative

unclassified drug

antiinfective agent

animal experiment

antibacterial activity

Article

bacterial strain

bone implant

bone regeneration

bone remodeling

cell adhesion

cell proliferation

controlled study

covalent bond

drug delivery device

drug efficacy

experimental infection

fluorescence microscopy

human

human cell

in vitro study

in vivo study

mouse

nonhuman

plate count

priority journal

reduction

titanium cage

animal

Bagg albino mouse

drug effects

female

microbial sensitivity test

Prosthesis-Related Infections

Animals

Anti-Infective Agents

Carbazoles

Mice

Inbred BALB C

Microbial Sensitivity Tests

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)