Targeted delivery of a photosensitizer to Aggregatibacter actinomycetemcomitans biofilm.
The ability to selectively target specific biofilm species with antimicrobials would enable control over biofilm consortium composition, with medical applications in treatment of infections on mucosal surfaces that are colonized by a mixture of beneficial and pathogenic microorganisms. We functionalized a genetically engineered multimeric protein with both a targeting moiety (biotin) and either a fluorophore or a photosensitizer (SnCe6). Biofilm microcolonies of Aggregatibacter actinomycetemcomitans, a periodontal pathogen, were targeted with the multifunctional dodecamer. Streptavidin was used to couple biotinylated dodecamer to a biotinylated anti-A. actinomycetemcomitans antibody. This modular targeting approach enabled us to increase the loading of photosensitizer onto the cells by a cycle of amplification. Scanning laser confocal microscopy was used to characterize transport of fluorescently tagged dodecamer into the microcolonies and targeting of the cells with biotin-labeled, fluorescently tagged dodecamer. Light-induced activity of the targeted photosensitizer reduced the viability of A. actinomycetemcomitans biofilm, as indicated by membrane permeability to propidium iodide. The functionalized multimeric protein promises to be a useful tool for controlling periodontal biofilm consortia and offers a modular design whereby moieties that target different species can be readily combined with the functionalized protein construct.
Suci
Peter
P
Department of Plant Sciences, Montana State University, Bozeman, MT 59717, USA. peter_s@erc.montana.edu
Kang
Sebyung
S
Gmür
Rudolf
R
Douglas
Trevor
T
Young
Mark
M
D000189:Actinobacillus Infections / Q000188:drug therapy / Q000382:microbiology; D016976:Aggregatibacter actinomycetemcomitans / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000907:Antibodies, Bacterial / Q000008:administration & dosage; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D018441:Biofilms / Q000254:growth & development; D001710:Biotin / Q000737:chemistry; D017931:DNA Primers / Q000235:genetics; D004337:Drug Carriers; D006801:Humans; D066298:In Vitro Techniques; D008087:Listeria / Q000737:chemistry / Q000235:genetics; D008665:Metalloporphyrins / Q000008:administration & dosage; D015661:Pasteurellaceae / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D010510:Periodontal Diseases / Q000188:drug therapy / Q000382:microbiology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D017931:DNA Primers; D004337:Drug Carriers; D008665:Metalloporphyrins; D017319:Photosensitizing Agents; D011994:Recombinant Proteins; C069117:tin(IV) chlorin e6; D001710:Biotin
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