Abstract
Misuse and overuse of antibiotics have contributed in the last decades to a phenomenon known as antibiotic resistance which is currently considered one of the principal threats to global public health by the World Health Organization. The aim to find alternative drugs has been demonstrated as a real challenge. Thanks to their biodiversity, insects represent the largest class of organisms in the animal kingdom. The humoral immune response includes the production of antimicrobial peptides (AMPs) that are released into the insect hemolymph after microbial infection. In this review, we have focused on insect immune responses, particularly on AMP characteristics, their mechanism of action and applications, especially in the biomedical field. Furthermore, we discuss the Toll, Imd, and JAK-STAT pathways that activate genes encoding for the expression of AMPs. Moreover, we focused on strategies to improve insect peptides stability against proteolytic susceptibility such as D-amino acid substitutions, N-terminus modification, cyclization and dimerization.
Highlights
The antibiotic resistance as a global concernToday, the identification of novel antibacterial therapeutics represents an auspicious perspective [1]
Due to the relevance of antimicrobial peptides (AMPs) function in insects, we focused on insect AMPs with a special emphasis on their classification, overviewing their structural and functional characteristics, along with reviewing the signaling pathways which activate the encoding AMP genes and their mechanism of action
Most insect AMPs are cationic due to the presence of basic residues in their amino acid sequences. They are positively charged at physiological pH, and the positive net charge facilitates their binding to negatively charged microbial surfaces through electrostatic interactions. Thanks to their antibacterial activity and to their ability to be active against fungi, viruses and some cancer cell lines, insect AMPs attract great attention in the biomedical field
Summary
The identification of novel antibacterial therapeutics represents an auspicious perspective [1]. Most insect AMPs are cationic molecules due to the presence of basic residues with activities against bacteria According to their amino acid sequences and structures, AMPs can be classified in four different groups: cysteinerich peptides (e.g. defensins), the α-helical peptides (e.g. cecropins), glycine (Gly) -rich proteins (e.g. attacins), and proline-rich peptides (e.g. drosocins) [86, 87]. AMPs lead to bacterial death by interacting with intracellular targets, as observed, for example, for the Temporin L peptide derived from Rana temporaria It inhibits cell division by binding the FtsZ protein that is the key factor of the divisome complex and is essential in Z-ring formation in E. coli [173]. Very interesting studies showed the antibiofilm performances of a complex mixture of defensin, cecropin, diptericin, proline-rich, and domesticin-like peptides, induced by C. vicina immune response after E. coli M17 strain infection. The clinical use of insect AMPs is really limited because of lacking information concerning bioavailability, instability to proteases, toxicity and side effects [228]
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