tachyplesin-peptide--tachypleus-tridentatus and mastoparan

With the increasing rate of antibiotic resistance in Acinetobacter, the World Health Organization introduced the carbapenem-resistant isolates in the priority pathogens list for which innovative new treatments are urgently needed. Antimicrobial peptides (AMPs) are one of the antimicrobial agents with high potential to produce new anti-Acinetobacter drugs. This review aims to summarize recent advances and compare AMPs with anti-Acinetobacter baumannii activity.. Active AMPs against Acinetobacter were considered, and essential features, including structure, mechanism of action, anti-A. baumannii potent, and other prominent characteristics, were investigated and compared to each other. In this regard, the Google Scholar search engine and databases of PubMed, Scopus, and Web of Science were used.. Forty-six anti-Acinetobacter peptides were identified and classified into ten groups: Cathelicidins, Defensins, Frog AMPs, Melittin, Cecropins, Mastoparan, Histatins, Dermcidins, Tachyplesins, and computationally designed AMPs. According to the Minimum Inhibitory Concentration (MIC) reports, six peptides of Melittin, Histatin-8, Omega76, AM-CATH36, Hymenochirin, and Mastoparan have the highest anti-A. baumannii power against sensitive and antibiotic-resistant isolates. All anti-Acinetobacter peptides except Dermcidin have a net positive charge. Most of these peptides have alpha-helical structure; however, β-sheet and other structures have been observed among them. The mechanism of action of these antimicrobial agents is divided into two categories of membrane-based and intracellular target-based attack.. Evidence from this review indicates that AMPs would be likely among the main anti-A. baumannii drugs in the post-antibiotic era. Also, the application of computer science to increase anti-A. baumannii activity and reduce toxicity could be helpful.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; beta-Lactam Resistance; Carbapenems; DNA-Binding Proteins; Drug Resistance, Bacterial; Histatins; Humans; Intercellular Signaling Peptides and Proteins; Microbial Sensitivity Tests; Peptides, Cyclic; Pore Forming Cytotoxic Proteins; Wasp Venoms

In the horseshoe crab, bacterial lipopolysaccharide (LPS) induces exocytosis by granular hemocytes, resulting in the secretion of various defense molecules, such as lectins and antimicrobial peptides, via a G protein-mediating signaling pathway. This response is a key component of the horseshoe crab innate immune response against infectious microorganisms. Here, we report an endogenous amplification mechanism for LPS-induced hemocytes exocytosis. The concentration of LPS required for maximal secretion decreased in proportion to the density of hemocytes, suggesting the presence of a positive feedback mechanism for secretion via a mediator secreted from hemocytes. The exocytosed fluid of hemocytes was found able to induce hemocyte exocytosis in the absence of LPS. Furthermore, tachyplesin, a major antimicrobial peptide of hemocytes, was able to trigger exocytosis in an LPS-independent manner, which was inhibited by a phospholipase C inhibitor, U-73122, and a G protein inhibitor, pertussis toxin. Surface plasmon resonance analysis showed that tachyplesin directly interacts with bovine G protein. These findings suggest that the tachyplesin-induced hemocyte exocytosis also occurs via a G protein-mediating signaling pathway. We concluded that tachyplesin functions not only as an antimicrobial substance, but also as a secondary secretagogue of LPS-induced hemocyte exocytosis, leading to the amplification of the innate immune reaction at sites of injury.

Topics: Animals; Antimicrobial Cationic Peptides; Cattle; DNA-Binding Proteins; Exocytosis; GTP-Binding Proteins; Hemocytes; Horseshoe Crabs; Intercellular Signaling Peptides and Proteins; Lipopolysaccharides; Peptides; Peptides, Cyclic; Signal Transduction; Wasp Venoms