Abstract
Antibiotic resistance represents a tremendous contemporary clinical challenge. Given this challenge, antimicrobial peptides (AMPs) are regarded as one of the most promising new options for next-generation lead antibiotics. Here, we describe the antibacterial activities of a cationic peptide named DRP-AC4, obtained from frog skin secretion using shotgun cloning. Two modified peptides were derived by substituting the sequence of amino acids to complete the hydrophobic face (DRP-AC4b) and increase net charge (DRP-AC4a), respectively. The activity and cytotoxicity of these two peptides were compared. DRP-AC4a displayed significantly increased potency against bacteria compared to the natural peptide. It should be noted, however, that both analogue peptides demonstrated higher lytic ability than the natural peptide against the membranes of mammalian erythrocytes. At the same time, all three peptides displayed lower hemolytic activity compared to their antibacterial activity. Here, we demonstrate that AMPs have more complex activity mechanisms and faster bactericidal rates than traditional antibiotics, which may be one of the reasons why bacteria do not develop resistance to them. These discoveries provide interesting insights into the discovery and development of novel drugs from natural sources.
Highlights
Since Fleming’s discovery of penicillin in 1928, antibiotics have been widely used to treat infectious diseases in humans and animals for nearly 100 years [1]
A peptide precursor encoding a putative novel peptide named DRP-4 was identified through translation of a cDNA, which was repeatedly cloned from a skin secretion-derived cDNA library of A. callidryas (Figure 1)
Theserial serial passages of DRP-AC4 andtwo theanalogues two analogues did not specific increase specificresistance bacterial. These results provided further support for the hypothesis resistance. These results provided further support for the that bacteria that readily develop drugdevelop resistance to traditional butantibiotics not to antimicrobial peptides (AMPs), phenomenon hypothesis bacteria readily drug resistance antibiotics to traditional butanot to AMPs, a which may be related to the rapid sterilisation rate and more elaborate action mechanism of phenomenon which may be related to the rapid sterilisation rate and more elaborate action mechanism of AMPs
Summary
Since Fleming’s discovery of penicillin in 1928, antibiotics have been widely used to treat infectious diseases in humans and animals for nearly 100 years [1]. Antibiotics have always played an essential role in protecting human health. Due to the emergence of a large number of resistant bacteria, antibiotics have gradually lost their antibacterial utility [2,3]. The development of new antibiotics or other antibacterial substances has become an urgent problem to be solved by the biomedical community [4]. AMPs are an indispensable and vital part of the innate immune systems of humans, animals and plants [6], and demonstrate a broad spectrum of activity and high potency against bacteria, fungi, Antibiotics 2020, 9, 243; doi:10.3390/antibiotics9050243 www.mdpi.com/journal/antibiotics
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