Development of Novel Antimicrobials using CRISPR-Cas Technology


Eftekhari N., Yaşa İ. , Eren A. E.

IV. Uluslararası Biyosidal Kongresi, Antalya, Turkey, 25 - 29 March 2018, pp.157

  • Publication Type: Conference Paper / Summary Text
  • City: Antalya
  • Country: Turkey
  • Page Numbers: pp.157

Abstract

Aim: Antimicrobial resistance especially antibiotic resistance is one of the biggest problems that triggered many challenges in treating bacterial infections. This problem is exacerbated due to the lack of newly developed antibiotics or approved for human use. To counteract the antibiotic resistance problem, alternative approaches have been developed in the recent years. Such approaches includes bioengineered and biologically inspired synthetic peptides, engineered bacteriophages and CRISPR technology. The possibility of designing novel antimicrobials against antibiotic resistant bacteria is according to the ability of CRISPR system in selecting any gene of interest as a target. By this way these antimicrobials targeting specifc DNA sequences genes which could be capable for killing just the bacteria that harbor this genes without affecting on the other neighboring bacteria, even in complex bacterial populations such as bioflms or the human microbiota. Method: These sequence-specifc antibiotics operate by designing the RNA-guided nuclease to develop antimicrobials with the activity of programmable function against specifc DNA sequences. Sequence-specifc nucleases delivered by phages or phage-derived particles. This RNA-guided nuclease utilized as novel antimicrobial for cleavage the targeted DNA which encode antibiotic resistance or virulence. Results: Based on observed results of CRISPR-CAS technology, reprogrammed Guide-RNA targeting virulence genes could affect only virulence genes in Staphylococcus aureus. Also reprogramming the guide-RNA nuclease to target antibiotic resistance genes, destroyed staphylococcal plasmids harboring these genes. In conclusion this method could be usable to decrease prevalence of the other antibiotic resistant pathogens like E.coli and Salmonella spp. It also increases the ability of manipulate complex bacterial populations for further studies on this method. Keywords: CRISPR-Cas, Guide-RNA, Antimicrobial, Resistance