Release date: 2018-01-24 Since the invention of antibiotics, multidrug-resistant bacteria (MDRB) are breaking through the last line of antibiotics, which has forced scientists to find new antibiotic compounds from toxic frogs, bacteria in the soil and other wildlife. Scientists have recently discovered a special microbial killer that designs a new drug that can eliminate stubbornness by adjusting the structure of a naturally occurring polypeptide (LL-37, a short-chain amino acid) found in the human body. MDRB. Kim Lewis, a microbiologist at Northeastern University in Boston, said the new drug is undergoing a human skin infection test, which will take a new step in overcoming the difficulty of creating the perfect antibiotic. As soon as a small percentage of the bacteria survived antibiotic treatment, the infection immediately lost control. These multi-drug resistant bacteria can accumulate on wound surfaces or medical devices and wrap themselves in a layer of slimy protective film (biofilm). Drugs are difficult to penetrate, and they will dormant, avoid antibiotic attacks, and then come back. Peter Nibbering, an immunologist at the University of Leiden Medical Center in the Netherlands, said the infection was very troublesome for the patient. Nibbering and a Dutch scientific team are fighting the infections associated with these biofilms by improving the human antibacterial peptide LL-37, which helps the body regulate the immune response. LL-37 already has some natural bactericidal ability, and it has been reported that the antibacterial effect is stronger by truncating the LL-37 structure. Inspired, Nibbering optimized them by performing a series of random replacements on the LL-37 polypeptide chain without destroying its overall structure. A derivative called SAAP-148 was produced, and the related content was published in Science Translational Medicine. The original text is at the end of the article. Unlike most traditional antibiotics, traditional antibiotics target specific bacterial populations and kill bacteria by destroying the key structures of these microbes, while SAAP-148 acts more broadly by destroying the plasma membrane of most bacteria. The contents of the cell were leaked and killed. Compared to the human antimicrobial peptide LL-37, SAAP-148 is more effective at killing bacteria under physiological conditions in vitro than many known pre-clinical and clinical stages of antimicrobial peptides. SAAP-148 kills MDRB without causing drug resistance and prevents biofilm formation and eliminates established biofilms and dormant bacteria. After a single 4-hour treatment with a hypromellose ointment containing SAAP-148, acute methicillin-resistant Staphylococcus aureus and MDR Acinetobacter baumannii infection in human skin wounds and mouse skin can be completely cured. These data indicate that SAAP-148 is a potential drug candidate against drug-resistant bacteria that pose a serious threat to human health. It also eliminates residual bacteria in bacterial biofilms that have been treated with rifampicin. Bob Hancock, a microbiologist at Columbia University in Vancouver, Canada (their team is also developing antibacterial peptides) pointed out that this would be the first antimicrobial peptide to eliminate dormant bacteria. Hancock said, "SAAP-148 seems to have overcome the "big trouble" of antibiotics: the environment in the human body inhibits the activity of many drug molecules because these drugs bind to proteins and lipids in the blood." . He pointed out that SAAP-148 appears to be one of the few known antimicrobial peptides that effectively kill bacteria and does not bind to these obstacles in serum. Colleagues also pointed out that SAAP-148 did not develop resistance after repeated treatment with S. aureus infection. Tim Tolker-Nielsen, a microbiologist at the University of Copenhagen Biofilm Research Center, said it was a surprise, although he noticed that Staphylococcus aureus could still develop resistance under some conditions. . Currently, Nibbering's team and a company called Madam Therapeutics are implementing SAAP-148 to treat local infections such as skin wounds, bladder infections or infections in the prosthesis. In order to be able to apply this drug systemically, they are designing an injectable formulation to protect SAAP-148 from being broken down in the body, allowing it to be selectively directed to the site of infection. Once approved by the ethics review board, Nibbering's plan can be quickly implemented in clinical trials, so stay tuned. Source: Medical Valley Zhoushan Fudan Tourism CO., LTD , https://www.fudanfood.com
