Blocks Important Enzymes "Starve" Pathogens

Antibiotics were once a "secret weapon" for humans to fight many diseases. In the late 19th and early 20th centuries, due to the discovery of a series of antibiotics, human lifespan was greatly improved. But it was less than a century since it was invented. Because of the increasing resistance of bacteria to antibiotics, antibiotics have gradually stepped down from the "sacred altar" and even become a major challenge in the field of medical and health care in the future.

The effectiveness of antibiotics is generally declining. The reason is that antibiotic-resistant bacteria are spreading rapidly, and resistant bacteria are not killed by certain antibiotics, and then they are no longer restricted and their resistance is even transmitted. Because of the resistance to antibiotics, some common pathogens are becoming so-called "super bacteria". Once antibiotics fail, our lives are fraught with danger-minor abrasions can lead to death, and minor ear infections can cause deafness.

The problem of antibiotic resistance has increasingly become a problem that plagues countries around the world. The World Health Organization has published a report saying that by 2050, bacterial resistance to antibiotics will kill 10 million people every year, equivalent to one person losing their life every 3 seconds, and the harm will exceed cancer. At the same time, the most worrying thing is that this harmfulness is increasing year by year. For example, the treatment of E. coli is usually effective with ordinary antibiotics, but in recent years, many countries have reported that some patients even use the most powerful antibiotics to no avail. At present, approximately 25,000 people are killed each year in Europe, causing 1.5 billion euros in annual medical costs and economic losses in the EU. Globally, about 700,000 people die from various drug-resistant infections every year, and 230,000 Newborns died as a result.

Antibiotic resistance has become one of the world's difficult problems. But recently, good news came from the Technical University of Munich, Germany. A team of chemists at the school proposed a new method: they have identified important enzymes in the metabolism of S. aureus. Breaking these enzymes can starve the pathogen.

"Many bacteria have developed resistance to broad-spectrum drugs, and an important goal of this research is to find new points of attack." Professor Stephan Sieber of the Technical University of Munich, together with his doctoral student Annabelle Hoegl and others, developed an isolation And the method of metabolizing enzymes, which can control the metabolic process, and if they are blocked, they can "starve" the pathogen more or less.

Their latest study tested S. aureus. This bacterium is made up of thousands of proteins and is ubiquitous in the world, and some S. aureus species are resistant to antibiotics. Stephan Sieber said that being able to isolate needles with characteristic properties in a haystack, identifying them, and investigating their functionality is a real challenge.

In this experiment, researchers used vitamin B6 to accelerate intracellular chemical reactions. A key component of vitamin B6 is pyridoxal phosphate (PLP). Without pyridoxal phosphate-dependent enzymes, the bacterial metabolism would Interruptions can cause bacteria to starve to death.

The team then used chemically modified pyridoxal phosphate to detect PLP-dependent enzymes, and the labeled molecules were placed in the nutrient solution of S. aureus. Because the nutrient solution does not contain natural pyridoxal phosphate, PLP-dependent enzymes will bind to these labeled molecules, and the researchers will then use an ultrasonic device to break down these bacteria and pick out the enzymes that carry the label. The basic principle of molecular selection is also called "protein profiling". This is not a new technology, but scientists at the Technical University of Munich have used this method for the first time to investigate and analyze PLP-dependent enzymes.

Stephan Sieber said: "We can confirm that this method is very effective and feasible. Many important enzyme substances in staphylococci rely on pyridoxal phosphate. We selected and isolated 73% of the enzymes and identified them by mass spectrometry.

In addition, the researchers discovered previously unknown PLP-dependent enzymes and deciphered their function. Stephan Sieber sees the search for new antibiotic targets as a treasure trove.

This discovery can be used to develop new antibacterial active drugs. In the next step, researchers hope to study the functionality of enzymes in more detail and determine how to block the metabolism of bacteria in a targeted manner without harming the health of human cells.