Stinky frogs are a treasure trove of antibiotic substances
Some of the nastiest smelling creatures on Earth have skin that produces the greatest known variety of anti-bacterial substances that hold promise for becoming new weapons in the battle against antibiotic-resistant infections, scientists are reporting. Their research on amphibians so smelly (like rotten fish, for instance) that scientists term them "odorous frogs" appears in ACS' Journal of Proteome Research.
Yun Zhang, Wen-Hui Lee and Xinwang Yang explain that scientists long have recognized frogs' skin as a rich potential source of new antibiotics. Frogs live in warm, wet places where bacteria thrive and have adapted skin that secretes chemicals, known as peptides, to protect themselves from infections. Zhang's group wanted to identify the specific antimicrobial peptides (AMPs), and the most potent to give scientists clues for developing new antibiotics.
They identified more than 700 of these substances from nine species of odorous frogs and concluded that the AMPs account for almost one-third of all AMPs found in the world, the greatest known diversity of these germ-killing chemicals. Interestingly, some of the AMPs have a dual action, killing bacteria directly and also activating the immune system to assist in the battle.
Peptide agents are regarded as hopeful candidates to solve life-threatening resistance of pathogenic microorganisms to classic antibiotics due to their unique action mechanisms. Peptidomic and genomic investigation of natural antimicrobial peptides (AMPs) from amphibian skin secretions can provide a large amount of structurefunctional information to design peptide antibiotics with therapeutic potential. In the present study, we identified a large number of AMPs from the skins of nine kinds of Chinese odorous frogs. Eighty AMPs were purified from three different odorous frogs and confirmed by peptidomic analysis. Our results indicated that post-translational modification of AMPs rarely happened in odorous frogs. cDNAs encoding precursors of 728 AMPs, including all the precursors of the confirmed 80 native peptides, were cloned from the constructed AMP cDNA libraries of nine Chinese odorous frogs. On the basis of the sequence similarity of deduced mature peptides, these 728 AMPs were grouped into 97 different families in which 71 novel families were identified. Out of these 728 AMPs, 662 AMPs were novel and 28 AMPs were reported previously in other frog species. Our results revealed that identical AMPs were widely distributed in odorous frogs; 49 presently identified AMPs could find their identical molecules in different amphibian species. Purified peptides showed strong antimicrobial activities against 4 tested microbe strains. Twenty-three deduced peptides were synthesized and their bioactivities, including antimicrobial, antioxidant, hemolytic, immunomodulatory and insulin-releasing activities, were evaluated. Our findings demonstrate the extreme diversity of AMPs in amphibian skins and provide plenty of templates to develop novel peptide antibiotics.