Scientists have created a method to make fully synthetic bacteriophage genomes and to add or remove individual genes. They modelled the synthetic DNA on two naturally occurring phages that infect Mycobacterium, a group that includes the pathogens for tuberculosis and leprosy, and published their findings in the Proceedings of the National Academy of Sciences. The work responds to a growing need for alternatives as antibacterial resistance increases.
High GC content makes some phage genomes hard to build: these Mycobacterium phages are about 65% G and C, while genomes with more even base ratios, such as E. coli, are easier to edit. Graham Hatfull worked with Greg Lohman and Ansa Biotech, and Ching‑Chung Ko is the paper’s first author. The team chemically synthesized genomes identical to two natural phages, BPs and Bxb1, built each genome in 12 sections and inserted those sections into a cell. The cell followed the instructions in the new genome and produced phages.
Precise genome changes let researchers remove or change specific genes and then observe the effects. That will help to understand phage biology and may enable engineered phages with wider clinical uses. Hatfull’s lab also keeps a large archive of phages and genomes, and synthetic genomes could speed patient matching and reduce the need to store many physical samples.
Difficult words
- bacteriophage — a virus that infects bacteria
- synthetic — made by people, not naturally produced
- pathogen — a microbe that causes disease in peoplepathogens
- resistance — ability of bacteria to survive drug treatment
- gc content — the proportion of guanine and cytosine bases
- genome — the complete set of an organism's DNAgenomes
- synthesize — to make a substance by chemical methodssynthesized
- archive — a stored collection of historical or scientific samples
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- How could engineered phages be useful in hospitals or clinics? Give one possible example and reason.
- What are the advantages of using synthetic genomes instead of storing many physical phage samples?
- The article says antibacterial resistance is increasing. What other alternatives to antibiotics can you imagine, and why might they help?
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