toxins Review Insect Antimicrobial Peptides, a Mini Review Qinghua Wu 1,2, Jiˇrí Patoˇcka 3,4 and Kamil Kuˇca 2,* 1 College of Life Science, Yangtze University, Jingzhou 434025, China; [email protected] 2 Department of Chemistry, Faculty of Science, University of Hradec Kralove, 500 03 Hradec Kralove, Czech Republic 3 Department of Radiology and Toxicology, Faculty of Health and Social Studies, University of South Bohemia, 370 05 Ceske Budejovice, Czech Republic; [email protected] 4 Biomedical Research Centre, University Hospital, 500 03 Hradec Kralove, Czech Republic * Correspondence: [email protected] Received: 20 September 2018; Accepted: 5 November 2018; Published: 8 November 2018 Abstract: Antimicrobial peptides (AMPs) are crucial effectors of the innate immune system. They provide the first line of defense against a variety of pathogens. AMPs display synergistic effects with conventional antibiotics, and thus present the potential for combined therapies. Insects are extremely resistant to bacterial infections. Insect AMPs are cationic and comprise less than 100 amino acids. These insect peptides exhibit an antimicrobial effect by disrupting the microbial membrane and do not easily allow microbes to develop drug resistance. Currently, membrane mechanisms underlying the antimicrobial effects of AMPs are proposed by different modes: the barrel-stave mode, toroidal-pore, carpet, and disordered toroidal-pore are the typical modes. Positive charge quantity, hydrophobic property and the secondary structure of the peptide are important for the antibacterial activity of AMPs. At present, several structural families of AMPs from insects are known (defensins, cecropins, drosocins, attacins, diptericins, ponericins, metchnikowins, and melittin), but new AMPs are frequently discovered. We reviewed the biological effects of the major insect AMPs. This review will provide further information that facilitates the study of insect AMPs and shed some light on novel microbicides. Keywords: antimicrobial peptides; AMP; Structure-activity relationship; modification; mechanism of action Key Contribution: The biological effects, especially the antibacterial activity of the major insect antimicrobial peptides (AMPs) are reviewed. 1. Introduction Antimicrobial peptides (AMPs) are multifunctional components of the innate immune defense systems in prokaryotic and eukaryotic organisms [1]. Based on amino acid substitutions, AMPs are divided into several subgroups. They generally consist of between 12 and 50 amino acids and are divided into subgroups by their amino acid composition and structure. Some AMPs can be as short as 7 to 100 amino acids [2]. The hydrophobic part of their molecule generally takes up more than 50% of amino acids residues. The secondary structure of AMPs follows four themes: (1) α-helical due to the presence of coiled conformation; (2) β-stranded; (3) β-hairpin or loop; and (4) extended conformation [3]. AMPs have a range of antibacterial, antifungal, and antiviral activities. They have a promising capacity in the therapeutic and prophylactic applications [4,5]. Moreover, AMP-derived drugs are administered as topical formulations to treat skin and wound infections [6]. Some AMPs also show anticancer effects or have anticancer properties [7]. Aurein, for example, is highly effective against Toxins 2018, 10, 461; doi:10.3390/toxins10110461 www.mdpi.com/journal/toxins Toxins 2018, 10, 461 2 of 17 Toxins 2018, 10, x FOR PEER REVIEW 2 of 16 around 50 different cancer cell lines and displays little toxicity [8]. Bacteria do not develop resistance to AMPS as easily as to traditional antibiotics. These peptides can physically disrupt microbial cellular resistance to AMPS as easily as to traditional antibiotics. These peptides can physically disrupt membranes and therefore kill a broad spectrum of pathogenic microorganisms. Thus, the microbial microbial cellular membranes and therefore kill a broad spectrum of pathogenic microorganisms. membrane is usually considered the primary target of AMPs [9,10]. Moreover, their outstanding Thus, the microbial membrane is usually considered the primary target of AMPs [9,10]. Moreover, membrane disruptive activity makes these peptides ideal candidates for combined therapies with their outstanding membrane disruptive activity makes these peptides ideal candidates for combined conventional antibiotics [11]. AMPs can facilitate more antibiotic molecules entering the microorganism therapies with conventional antibiotics [11]. AMPs can facilitate more antibiotic molecules entering cytoplasm, where they can interact with their target (Figure1). the microorganism cytoplasm, where they can interact with their target (Figure 1). Figure 1.1. CombinedCombinedeffects effects of of antimicrobial antimicrobial peptides peptides (AMPs) (AMPs) and and antibiotics antibiotics on bacteria.on bacteria. (A) AMPs(A) AMPs can disruptcan disrupt the bacterial the bacterial membrane membrane to cause to thecause leakage the le ofakage the cellof the content cell intoconten thet extracellularinto the extracellular medium andmedium kill the and bacteria. kill the The bacteria. AMPs The can AMPs facilitate can more facilit antibioticsate more toantibiotics enter the cytoplasmto enter the of cytoplasm bacteria and of finallybacteria interact and finally with their interact target. with However, their target. the leakage However, of the antibioticsthe leakage from of thethe cytoplasmantibiotics should from notthe becytoplasm ignored; should (B) in bacterial not be ignored; cells, antibiotics (B) in bacterial are pumped cells, outantibiotics of the cells are bypumped the multidrug out of the efflux cells pumps, by the whichmultidrug is how efflux bacteria pumps, exert which their is resistance how bacteria properties exert their (adapted resistance from [properties11]). (adapted from [11]). AMPs kill bacteriabacteria viavia aa varietyvariety ofof mechanismsmechanisms includingincluding membranemembrane disruption,disruption, interferenceinterference withwith bacterialbacterial metabolism,metabolism, and targeting of cytoplasmiccytoplasmic components [[5,6,10,12–14].5,6,10,12–14]. The primaryprimary contact between an AMP and thethe targettarget bacteriumbacterium occursoccurs viavia anan electrostaticelectrostatic oror hydrophobichydrophobic interaction,interaction, which is strongly dependent on the lipid composition of the bacterial membrane [15,16]. [15,16]. AMPsAMPs areare capablecapable of of interacting interacting with with the the surface surface of of the the cell cell membrane membrane to alterto alter the the permeability permeability of the of membranethe membrane [10]. [10]. After After AMPs AMPs interact interact with the with cell the membrane, cell membrane, the formed the transmembrane formed transmembrane potential affectspotential the affects osmotic the pressure osmotic balance pressure [6]. balance In short, [6]. the In interaction short, the between interaction the AMPs between and the the AMPs membrane and isthe directly membrane related is todirectly the antibacterial related to activitythe antibacteria of the AMPs.l activity At present, of the AMPs. there are At at present, least four there modes are ofat actionleast four commonly modes of used action to describe commonl they membraneused to describe activity the of membrane AMPs: Barrel-stave, activity of carpet,AMPs: toroidal-pore, Barrel-stave, andcarpet, disordered toroidal-pore, toroidal-pore and disord [10,12ered]. For toroidal-pore all these modes, [10,12]. a threshold For all concentrationthese modes, is a required threshold to conductconcentration the antibacterial is required effectto conduct [10]. the AMPs antibacteria can alsol disrupt effect [10]. intracellular AMPs can enzymes also disrupt and intracellular DNA when theyenzymes translocate and DNA into when the pathogens they translocate [5]. The into detailed the pa explanationthogens [5]. ofThe these detailed modes explanation can be read of in these our recentmodes reviewcan be [6read] as wellin our other recent publications review [6] [5 as,10 ,well12,13 other]. Regarding publications the membrane [5,10,12,13]. activity Regarding of AMPs, the somemembrane issues activity need to of be AMPs, considered. some issues For example, need to be whether considered. there isFor a specificexample, membrane whether there receptor, is a andspecific whether membrane there are receptor, other factors and whether synergistically there are working other in factors this context. synergistically The mechanism working of in action this ofcontext. different The AMPs mechanism may be variable,of action and of furtherdifferent research AMPs ismay needed. be variable, and further research is needed. AMPs can be classified into many types, based on their secondary structures in liquid media [17,18]. The β-sheet peptides contain a disulfide bond that stabilizes the structure, and helps the Toxins 2018, 10, 461 3 of 17 AMPs can be classified into many types, based on their secondary structures in liquid media [17,18]. The β-sheet peptides contain a disulfide bond that stabilizes the structure, and helps the AMPs to cross the cell membrane. In addition to the β-sheet structure, AMPs also form an α-helical structure, and contain a cysteine in the peptide to form an intramolecular disulfide bridge [19,20]. Due to the presence of hydrophobic groups, the peptide chain forms a polymer by hydrophobic interaction to increase the affinity for cell membranes [6,21–23]. The optimum antibacterial activity appears