Development of New Antibiotics to Target Resistant Bacteria
Health professionals across the world are in urgent need of new antibiotics as the number of patients dying due to antibiotic-resistant bacteria is increasing annually. In a recent study, researchers from the University of Zurich and the Spexis company have come up with antimicrobial molecules that target the metabolism of bacteria. They modified the chemical structure of natural peptides, which insects use to defend themselves against infection, to develop the new antimicrobial molecules that can attack the DNA of Gram-negative bacteria in the same way, including the most dangerous ones.
Chemically Optimized Natural Peptide
The researchers started their study with a peptide called tanatin, which was found to disrupt an important lipopolysaccharide transport bridge between the outer and inner membrane of Gram-negative bacteria. However, thanatin has low efficacy and bacteria quickly develop resistance to it. Researchers modified the chemical structure of thanatin and used structural analysis to assemble the various components of the bacterial transport bridge. Nuclear magnetic resonance (NMR) was used for visualizing how thanatin binds to and disrupts the transport bridge. Spexis AG researchers then planned the necessary chemical modifications. The resulting synthetic peptides were tested in mice and yielded outstanding results. These new antibiotics have proven to be effective, safe, and immune to resistance, especially for treating lung infections. They are also highly effective against carbapenem-resistant Enterobacteriaceae, where most other antibiotics fail.
Effective against Resistant Bacteria
One of the major concerns associated with antibiotics is the development of resistant bacteria. The researchers were determined to choose the most promising peptides for their study to ensure they were also effective against bacteria that had already developed resistance to thanatin. The new class of antibiotics developed by the researchers has the prospect of becoming available and effective against resistant bacteria, thereby slowing down the development of antibacterial resistance.
Conclusion
Antibiotic resistance is one of the biggest threats to global health, food security, and development today. While researchers like the University of Zurich and Spexis company are working towards developing new antibiotics that can fight deadly drug-resistant infections, experts warn that this is a race against time. Many of the antibiotics that we have today, including the last line of defense, colistin, are failing against deadly antibiotic-resistant infections. Therefore, it is imperative that researchers continue to improve their understanding of how antibiotics work and develop new ones to tackle resistant bacteria.
Additional Piece – The Need for New Antibiotics
Antibiotic resistance is a growing threat, causing the estimated deaths of at least 700,000 people each year and warning that it could become a more severe problem than cancer by 2050. The development and spread of resistant bacteria pose a serious threat to human health, food security, and global health. Without immediate action, routine operations such as cancer treatment, organ transplants, and childbirth, and common infections like pneumonia and urinary tract infections (UTIs) could become fatal. Finding new antibiotics is therefore essential to combat resistant bacteria and prevent millions of deaths each year.
However, the development of new antibiotics is expensive and time-consuming, making it less attractive for pharmaceutical companies, given the high return on investment is uncertain. For example, in the last two decades, the number of new approved antibiotics has gone down, leading to a lack of effective antibiotics that can tackle resistant bacteria. Many of the broad-spectrum antibiotics given to patients today were developed in the 1950s and 1960s, and most of the new antibiotics are only modifications of existing ones. Additionally, the overuse and misuse of antibiotics have expedited the development of antibiotic-resistant bacteria, and the less these are prescribed, the less resistant bacteria will develop.
The immune system is highly complex, and its functioning capacity can diminish due to the development of resistant bacteria. Therefore, the development of new antibiotics is necessary, as it could provide new avenues of action to immune systems that do not work against resistant bacteria. Researchers worldwide are working tirelessly to develop new antibiotics that can fight resistant bacteria. They use several methods such as targeting the metabolism of bacteria, exploring host-pathogen interactions and developing alternatives such as probiotics, bacteriophages, and essential oils.
Antimicrobial resistance poses a significant public health issue globally. While there is still a long way to go in the development of new antibiotics, researchers remain hopeful that these new classes of antibiotics could help save millions of lives within a few years. Therefore, antibiotic stewardship is essential to ensure that the current drugs work effectively and to prevent the spread of resistance. We need to continue to work together to conserve what we have and develop new antibiotics to combat resistant bacteria.
Summary
Health professionals worldwide require new antibiotics to combat resistant bacteria, leading researchers to develop highly effective antimicrobial molecules that attack the metabolism of bacteria. To develop these synthetic peptides, scientists from the University of Zurich and the Spexis company performed structural analysis of natural peptides and assembled the various components of bacterial transport bridges. The result of the study yielded synthetic peptides that are effective, safe, and immune to resistance, especially against resistant bacteria.
Antibiotic resistance is a growing problem that could become a bigger threat than cancer by 2050, leading to more than 700,000 deaths each year. The development of new antibiotics is essential to combat resistance and prevent millions of deaths. The development of new antibiotics is expensive and time-consuming, but researchers are hopeful that new classes of antibiotics could save millions of lives within a few years. Maintaining the efficacy of existing antibiotics and prescribing them properly is essential to combating resistance and aiding the fight against resistant bacteria.
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Health professionals urgently need new antibiotics to combat resistant bacteria. Researchers from the University of Zurich and the Spexis company have now modified the chemical structure of natural peptides to develop antimicrobial molecules that bind to new targets in the metabolism of bacteria.
Every year, more than five million people around the world die as a result of bacteria resistant to the most common antibiotics. New antibiotics are urgently needed to ensure that bacterial infections in patients can still be successfully treated. “Unfortunately, the development pipeline for new antibiotics is pretty empty,” says chemist Oliver Zerbe, head of the NMR facility at the University of Zurich. “More than 50 years have passed since the last antibiotics against previously unused target molecules were approved.”
In a recently published study in Progress of science, Zerbe is now looking to develop a class of highly effective antibiotics that fight Gram-negative bacteria in a novel way. The WHO classifies this group of bacteria as extremely dangerous. The group, whose resistance is particularly high due to their double cell membrane, includes carbapenem-resistant Enterobacteriaceae, for example. In addition to the UZH team, researchers from the pharmaceutical company Spexis AG also participated in the study as part of a collaboration co-funded by Innosuisse.
Chemically optimized natural peptide
The starting point for the researchers’ study was a natural peptide called tanatin, which insects use to defend themselves against infection. Thanatin disrupts an important lipopolysaccharide transport bridge between the outer and inner membrane of Gram-negative bacteria, as revealed a few years ago in a study by now-retired UZH Professor John Robinson. As a result, these metabolites accumulate inside the cells and the bacteria die. However, thanatin is not suitable for use as an antibiotic drug, among other things because of its low efficacy and because bacteria quickly become resistant to it.
Therefore, the researchers modified the chemical structure of thanatin to improve the characteristics of the peptide. “To do this, structural analyzes were essential,” says Zerbe. Her team synthetically assembled the various components of the bacterial transport bridge and then used nuclear magnetic resonance (NMR) to visualize where and how thanatin binds to and disrupts the transport bridge. Using this information, the Spexis AG researchers planned the necessary chemical modifications to enhance the antibacterial effects of the peptide. More mutations were made to increase the stability of the molecule, among other things.
Effective, safe and immune to resistance.
The synthetic peptides were then tested in mice with bacterial infections and yielded outstanding results. “The new antibiotics have proven to be very effective, especially for treating lung infections,” says Zerbe. “They are also highly effective against carbapenem-resistant Enterobacteriaceae, where most other antibiotics fail.” In addition, the newly developed peptides are not toxic or harmful to the kidneys, and also proved to be stable in the blood for a longer period, all of which are properties that are required to gain drug approval. However, more preclinical studies are needed before the first human trials can begin.
By choosing the most promising peptides for their study, the researchers ensured that they would also be effective against bacteria that had already developed resistance to thanatin. “We are confident that this will significantly slow down the development of antibacterial resistance,” says Zerbe. “We now have the prospect of a new class of antibiotics becoming available that is also effective against resistant bacteria.”
https://www.sciencedaily.com/releases/2023/06/230601160147.htm
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