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   zinc finger nuclease: a new approach to overcome betalactam antibiotic resistance  
   
نویسنده shahbazi dastjerdeh mansoureh ,kouhpayeh shirin ,sabzehei faezeh ,khanahmad hossein ,salehi mansour ,mohammadi zahra ,shariati laleh ,hejazi zahra ,rabiei parisa ,manian mostafa
منبع jundishapur journal of microbiology - 2016 - دوره : 9 - شماره : 1 - صفحه:1 -11
چکیده    Background: the evolution of antibiotic-resistant bacteria (arb) and antibiotic-resistance genes (args) has been accelerated recently by the indiscriminate application of antibiotics. antibiotic resistance has challenged the success of medical interventions and therefore is considered a hazardous threat to human health. objectives: the present study aimed to describe the use of zinc finger nuclease (zfn) technology to target and disrupt a plasmid-encoded β-lactamase, which prevents horizontal gene transfer-mediated evolution of arbs. materials and methods: an engineered zfn was designed to target a specific sequence in the ampicillin resistance gene (amp^r) of the ptz57r plasmid. the escherichia coli bacteria already contained the pzfn kanamycin-resistant (kanar) plasmid as the case or the pp15a, kanar empty vector as the control, were transformed with the ptz57r; the ability of the designed zfn to disrupt the β-lactamase gene was evaluated with the subsequent disturbed ability of the bacteria to grow on ampicillin (amp) and ampicillin-kanamycin (amp-kana)-containing media. the effect of mild hypothermia on the zfn gene targeting efficiency was also evaluated. results: the growth of bacteria in the case group on the amp and amp-kana-containing media was significantly lower compared with the control group at 37°c (p < 0.001). despite being more efficient in hypothermic conditions at 30°c (p < 0.001), there were no significant associations between the incubation temperature and the zfn gene targeting efficiency. conclusions: our findings revealed that the zfn technology could be employed to overcome ampicillin resistance by the targeted disruption of the ampicillin resistance gene, which leads to inactivation of β-lactam synthesis. therefore, zfn technology could be engaged to decrease the antibiotic resistance issue with the construction of a zfn archive against different args. to tackle the resistance issue at the environmental level, recombinant phages expressing zfns against different args could be constructed and released into both hospital and urban wastewater systems.
کلیدواژه ampicillin resistance ,microbial drug resistance ,betalactamases ,gene targeting ,genome editing ,zinc finger nuclease
آدرس isfahan university of medical sciences, school of medicine, department of genetics and molecular biology, ایران, isfahan university of medical sciences, school of medicine, department of immunology, ایران, isfahan university of medical sciences, school of medicine, department of genetics and molecular biology, ایران, isfahan university of medical sciences, school of medicine, department of genetics and molecular biology, ایران, isfahan university of medical sciences, school of medicine, department of genetics and molecular biology, ایران, isfahan university of medical sciences, school of medicine, department of genetics and molecular biology, ایران, tehran university of medical sciences, school of advanced technologies in medicine, department of molecular medicine, ایران, isfahan university of medical sciences, school of medicine, department of genetics and molecular biology, ایران, isfahan university of medical sciences, school of medicine, department of genetics and molecular biology, ایران, isfahan university of medical sciences, school of medicine, department of immunology, ایران
 
     
   
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