Traditional antibiotics can cause bacteria to develop resistance, which can cause normal doses of antibiotics to no longer exert their expected bactericidal effects or even render drugs ineffective, posing an increasingly serious threat to people's health. In 2019, the "super bacteria" that developed resistance to antibiotics directly caused approximately 1.27 million deaths worldwide. Recently, Fun Science website in the United States reported that scientists are researching methods beyond traditional antibiotics to find new weapons that will not promote the rise of "super bacteria", including viruses that can kill bacteria, CRISPR found in prokaryotic cells, molecules that can kill bacteria, etc. Some of them have been tested on patients. Before the discovery of penicillin in 1928, the use of bacteriophages to combat bacteria was first proposed as a "surrogate" for antibiotics, known as bacteriophage therapy. Phages are viruses that can infect bacteria, typically killing them by invading their cells and dividing them from within. Phages can also force bacteria to surrender. There is a protein in Escherichia coli that acts as an efflux pump, which can pump antibiotics out of the cell. In order to penetrate into the body of Escherichia coli, bacteriophages use "efflux pumps". If Escherichia coli attempts to change this pump to avoid phage attacks, it will reduce its ability to pump out antibiotics. Paul Turner, director of the Center for Phage Biology and Therapy at Yale University, pointed out that unlike antibiotics, bacteria are unlikely to develop widespread resistance to bacteriophage therapy because the target of bacteriophages is even narrower than narrow-spectrum antibiotics, targeting only proteins found in one or several bacterial strains. In addition, although the target bacteria can still evolve resistance to individual bacteriophages, selecting the correct combination of bacteriophages can reduce bacterial virulence or increase susceptibility to antibiotics. The CRISPR technology, known as "gene magic scissors", is renowned as a powerful gene editing tool for enhancing bacteriophages using "gene magic scissors". It is actually adapted from the immune system found in many bacteria: CRISPR-Cas, and scientists are exploring the use of CRISPR-Cas to cut the DNA of bacterial cells. The true charm of this method is that it is a sequence specific tool, which means it only targets the target DNA, rather than sequences present in other bacteria. Therefore, once applied to patients, CRISPR will enter, attack, and kill cells with specific sequences. How to introduce CRISPR-Cas into the correct bacteria? Multiple research teams are testing different delivery methods, but the best strategy currently seems to be to load the CRISPR mechanism into phages that infect the target bacteria. A biotechnology company in the United States is currently testing CRISPR enhanced bacteriophage therapy on approximately 800 subjects, which combines the bactericidal ability of bacteriophages with CRISPR Cas's ability to destroy bacterial genes. Like phage therapy without CRISPR, scientists need to determine the safety and appropriate dosage of this therapy. In addition to phages and CRISPR, scientists are also developing alternative antibiotics to design molecules to kill bacteria
Edit：GuoGuo Responsible editor：FangZhiYou
Source：people.cn
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