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© Antoinette Ryter
Serratia marcescens avec présence de flagelles (cils) péritriches. Famille des Enterobacteriaceae, bacille à Gram négatif, non sporulé, anaérobie facultatif, mobile, parfois encapsulé, pouvant synthétiser un pigment rouge ou rose. Présent dans les végétaux , le sol, et l'eau. A l'origine d'infections nosocomiales et résistant à de nombreux antibiotiques. Image colorisée.
Publication : Nature biotechnology

Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials

Team: Synthetic Biology
Member: David Bikard
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature biotechnology - 05 Oct 2014

Bikard D, Euler CW, Jiang W, Nussenzweig PM, Goldberg GW, Duportet X, Fischetti VA, Marraffini LA

Link to Pubmed [PMID] – 25282355

Nat. Biotechnol. 2014 Nov;32(11):1146-50

Antibiotics target conserved bacterial cellular pathways or growth functions and therefore cannot selectively kill specific members of a complex microbial population. Here, we develop programmable, sequence-specific antimicrobials using the RNA-guided nuclease Cas9 (refs.1,2) delivered by a bacteriophage. We show that Cas9, reprogrammed to target virulence genes, kills virulent, but not avirulent, Staphylococcus aureus. Reprogramming the nuclease to target antibiotic resistance genes destroys staphylococcal plasmids that harbor antibiotic resistance genes and immunizes avirulent staphylococci to prevent the spread of plasmid-borne resistance genes. We also show that CRISPR-Cas9 antimicrobials function in vivo to kill S. aureus in a mouse skin colonization model. This technology creates opportunities to manipulate complex bacterial populations in a sequence-specific manner.