Fishing for new antibiotics
By : Emily Law
Exciting news in the battle to maintain the efficacy of antibiotics has been announced by CityU scientists investigating natural antibacterial agents in fish blood.
The team has identified a super antimicrobial peptide that can kill over 30 common bacteria. The peptide might be used to develop new drugs that can be combined with other antibiotics for better medical effect.
The research team, which named the super antimicrobial peptide “BING” (Blocker of the INtermembrane Stress Response in Gram Negative Bacteria), was inspired by the initial hypothesis that fish must possess a very strong immune system.
“That’s why we started to study the peptides contained in the blood of fish,” said Dr Lam Yun-wah, who has been working on this project along with fellow associate professors Dr Doris Au Wai-ting and Dr Sun Hongyan in the Department of Chemistry.
“Antimicrobial peptides are an important part of a living organism’s defense against bacteria,” Dr Lam explained.
Antibiotics were regarded as a “magic bullet” when they first appeared in the last century. Their potential to significantly reduce the number of deaths from bacterial infection was a major breakthrough in medical science. However, due to misuse over the years, antibiotics are losing their punch. In addition, the last new antibiotic was launched 30 years ago, mainly because of exceptionally high development costs, low returns, and no solution yet for the misuse of antibiotics. So now we are hearing more about resistance to antibiotics and an increasing number of super bugs rather than the introduction of new drugs. In fact, the United Nations has declared that antimicrobial resistance is one of the greatest threats to human health today.
“Antimicrobial peptides are an important part of a living organism’s defense against bacteria.” In response to the crisis, the CityU research team is working together on ways to mitigate this threat. The three researchers came together out of mutual interest in the topic and a strong desire to contribute to the mitigation of the antibiotics crisis and develop new drugs. Dr Lam is a biochemist, Dr Au focuses her research on marine organisms, while Dr Sun specialises in protein biochemistry.
Specifically Dr Lam and Dr Au investigate natural antibacterial agents among Hong Kong’s rich marine resources, Dr Lam said. Although fish have a very strong immune system, relevant research is relatively sparse. “Fish must have a very strong immune system judging by the amount of bacteria that they have to fight against in the oceans,” Dr Lam said.
Medaka, a small fish about 2 centimetres in length, is the focus of the study. Although each medaka has only 0.001ml of blood, antimicrobial peptides are present. However, critical information concerning the number and types of peptides in medaka has not yet been classified, which is where the CityU team comes in.
Using a technique called mass spectrometry, Dr Lam and his team first of all identified 6,399 types of peptide molecules in the blood of medaka and then conducted bioinformatics analysis to profile the physical and chemical features common to antimicrobial peptides. These processes enabled the team to predict which of the identified peptides were likely to possess the strongest antibacterial properties. As a result, they have set up the world’s largest collection of peptides in fish blood, with information on 430 previously unknown medaka peptides.
The next step was to see how well the new peptides could combat other bacteria. The team tested 53 of the 430 newly identified medaka peptides using two common bacteria, Staphylococcus aureus and Edwardsiella tarda. The results showed that eight of those 53 were particularly effective at neutralising these two common bacteria.
After further tests, the team identified one super antimicrobial peptide, BING, which can kill over 30 common bacteria, including Mycobacterium tuberculosis and most other pathogenic bacteria. The research team also managed to boost BING’s stability and ability of killing germs by 10 times by modifying BING’s chemical structure.
“Now we are studying how the eight peptides successfully kill off the Staphylococcus aureus and Edwardsiella tarda bacteria, and use our insights to develop new drugs,” Dr Lam said. “BING may reduce the effect of antimicrobial resistance, making existing antibiotics resume their functions against bacteria.”
Dr Lam said the research team would continue to study BING with the aim of developing new antibiotics. They would also study the other 380 or so peptides in medaka’s blood, hoping to identify more super antimicrobial proteins that can help solve the “threat of antibiotics resistance”.
