Israeli scientists have used a virus that infects bacteria to insert genes that make the bugs more susceptible to antibiotics. The researchers say the virus could be used to tackle antibiotic resistant superbugs that live in our hospitals.
A proof-of-concept study suggests that phage therapy might offer an approach to address the long-intractable problem of antibiotic resistance. Phage therapy, predicated on tailored viruses that target pathogenic bacteria, could help counter the surge of antibiotic resistance, but the strategy suffers from shortfalls, not least of which are the difficulty of delivering phages into infected tissues and the frequent transfer of phage-resistance genes between bacteria. Using lambda phage, Udi Qimron and colleagues transferred into the genome of antibiotic-resistant bacteria a CRISPR-Cas gene-editing system that was programmed to seek and disrupt genes encoding β-lactamase enzymes, which confer resistance to last-resort antibiotics. The authors also inserted identical β-lactamase-encoding CRISPR-Cas target sequences into T7 phages, which are lethal to bacteria. When grown on agar dishes coated with the modified T7 phages, bacteria containing the engineered lambda phage were found to be sensitive to the targeted antibiotics, and 20-fold more resistant to the engineered T7 phages compared with control bacteria, which remained antibiotic-resistant. Together, the phages selectively favored antibiotic-sensitive bacteria, suggesting that an approach that couples bacterial survival and antibiotic sensitivity might be used to treat exposed surfaces and hand sanitizers in hospitals, which are hotbeds of antibiotic resistance. The authors suggest that the use of phage mixtures, including mutant phages that infect many bacterial species, might help expand the narrow host range of phages and override bacterial resistance to phages, potentially surmounting longstanding hurdles to phage therapy.
