Build a arsenal for dealing with super bacteria

The World Tide of Technological InnovationReporter Liu Xia from our newspaperTraditional 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

The World Tide of Technological Innovation

Reporter Liu Xia from our newspaper

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.

Using bacteriophages to combat bacteria

Before the discovery of penicillin in 1928, a "substitute" for antibiotics was first proposed, 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.

Enhancing bacteriophages with "gene magic scissors"

The CRISPR technology, known as the "gene magic scissors," is renowned as a powerful gene editing tool that is actually adapted from the immune system discovered in many bacteria: CRISPR-Cas. 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.

Design molecules to kill bacteria

In addition to bacteriophages and CRISPR, scientists are also developing alternative antibiotics, such as bactericidal peptides (short chains of proteins) and enzymes (special proteins that initiate chemical reactions), which can target bacterial proteins that are less resistant to attack, killing bacteria with a very narrow range.

Peptide nucleic acid (PNA) molecules manufactured in the laboratory are one of the most promising candidates. These molecules can be programmed to prevent bacterial cells from constructing proteins crucial for their survival. PNA achieves this by locking in specific messenger ribonucleic acids (mRNA), which are genetic molecules carrying instructions for constructing proteins. However, PNA itself cannot enter bacterial cells, so it usually needs to attach to other peptides that are easy to pass through bacterial cell walls, allowing for a "free ride" into bacterial cells.

By targeting proteins that cells cannot change without harming themselves, PNA can avoid triggering drug resistance. Scientists can also genetically edit these molecules to target proteins that directly lead to antibiotic resistance.

Enzymes called lysozymes are another promising treatment option. In nature, bacteriophages use lysosomes to divide bacteria from within. They are like knives, cutting open the outer wall of bacterial cells and exposing their "internal organs". These "molecular knives" are unlikely to trigger drug resistance, as bacteria cannot easily alter the basic cell wall components targeted by lysosomes.

Lysoxins quickly kill bacteria when they come into contact with them, and they can accurately kill certain types of bacteria while turning a blind eye to other types of bacteria. In addition, scientists can adjust lysosomes in the laboratory to alter the bacteria they target, enhance their efficacy, and enhance their durability within the bacterial body.

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