Journal of Probiotics & Health
Open Access

Probiotic delivery for antibiotic resurrection via programmable RNA-guided endonuclease inactivation of resistance genes

6^th International Conference and Exhibition on Probiotics, Functional and Baby Foods

October 02-03, 2017 London, UK

Conrad Lichtenstein

Babraham Research Campus, UK

Posters & Accepted Abstracts: J Prob Health

Abstract :

We use bacterial cybergenetics to resurrect sensitivity to antibiotics in antimicrobial resistant (AMR) pathogens. Our â�?�?Nemesis Symbioticsâ�?, use a programmable RNAguided DNA endonuclease gene editing technology to target betalactamase (bla) resistance genes. By multiplexing guide RNA genes, we inactivate members of eight families of bla genes â�?�?VIM, OXA, NDM, CTXM, KPC, IMP, SHVand TEM (VONCKIST), so resurrecting sensitivity to a broad range of beta-lactam antibiotics. Transmids, our novel delivery vectors can be packaged in a bacteriophage coat to introduce Symbiotics by infection. Transmids also spread to other bacteria by plasmid conjugation. In a mouse model study, we show that Transmid delivery by conjugation from a probiotic donor strain introduced into the gut microbiome disarms a resident E. coli strain carrying a target AMR gene giving prophylactic applications in anticipation of opportunistic infections. Our experiments suggest that multifunctional gene targeting systems may obviate the need for prior diagnostic screens for antibiotic resistance and can be used generally as a companion biological therapeutic, together with well-established antibiotics, for both therapeutic treatment of infection as well as by prophylactic treatment in preventing the spread of AMR.