Natural Antimicrobial Peptides Research Articles

Hydrophobic interactions modulate antimicrobial peptoid selectivity towards anionic lipid membranes

Hydrophobic interactions govern specificity for natural antimicrobial peptides. No such relationship has been established for synthetic peptoids that mimic antimicrobial peptides. Peptoid macrocycles synthesized with five different aromatic groups are investigated by minimum inhibitory and hemolytic concentration assays, epifluorescence microscopy, atomic force microscopy, and X-ray reflectivity. Peptoid hydrophobicity is determined using high performance liquid chromatography. Disruption of bacterial but not eukaryotic lipid membranes is demonstrated on the solid supported lipid bilayers and Langmuir monolayers. X-ray reflectivity studies demonstrate that intercalation of peptoids with zwitterionic or negatively charged lipid membranes is found to be regulated by hydrophobicity. Critical levels of peptoid selectivity are demonstrated and found to be modulated by their hydrophobic groups. It is suggested that peptoids may follow different optimization schemes as compared to their natural analogues.

Evaluation on the effects of 0.1% Peumus boldus leaf and Spiraea ulmaria plant extract combination on bacterial colonization in canine atopic dermatitis: A preliminary randomized, placebo controlled, double-blinded study

Defective skin barrier characterize canine atopic dermatitis (AD). Pyoderma is the most common complication. Herbal compounds have been suggested as alternatives to control bacterial colonization for their effect on natural antimicrobial peptides (AMPs). This study evaluated the effects of 0.1% Peumus boldus leaf and Spiraea ulmaria plant extract combination on clinical signs, bacterial colonization and AMPs secretion in atopic dogs compared to placebo.Twenty privately-owned atopic dogs were randomly divided in 2 groups (treatment: n = 10; placebo: n = 10) and their abdomen was sprayed every 24 h for 4 weeks. Total and inguinal clinical scores (CADESI-03), manual bacterial count, and skin washes for AMPs (cBD3-like and cCath) were performed on days 0, 14 and 28. AMPs were detected using in-house, previously-validated, canine-specific ELISAs. Data were statistically analyzed and a p < 0.05 was considered significant.Clinical scores and AMPs secretion did not differ significantly between the two groups at any time point. A significant reduction of the clinical scores was seen in the placebo group at 14 and 28 days (p < 0.04). On days 14 and 28, a reduction in the bacterial count was seen in the treated group compared with placebo (p < 0.009 and p = 0.04, respectively). Compared to baseline, a reduction in Staphylococcus spp. was seen in the treated group after 14 days of treatment (p < 0.03).These results show the efficacy of this plant extract combination against bacterial colonization, suggesting its potential usefulness in preventing bacterial infection in atopic dogs. The influence of this compound on AMPs secretion or other mechanisms should be further evaluated.

A New Method of Producing a Natural Antibacterial Peptide by Encapsulated Probiotics Internalized with Inulin Nanoparticles as Prebiotics.

Synbiotics are a combination of probiotics and prebiotics, which lead to synergistic benefits in host welfare. Probiotics have been used as an alternative to antibiotics. Among the probiotics, Pediococcus acidilactici (PA) has shown excellent antimicrobial activity against Salmonella Gallinarum (SG) as a major poultry pathogen and has improved the production performances of animals. Inulin is widely used as a prebiotic for the improvement of animal health and growth. The main aim of this study is to investigate the effect of the antimicrobial activity of inulin nanoparticles (INs)-internalized PA encapsulated into alginate/chitosan/alginate (ACA) microcapsules (MCs) in future in vivo application. The prepared phthalyl INs (PINs) were characterized by DLS and FE-SEM. The contents of phthal groups in phthalyl inulin were estimated by ¹H-NMR measurement as 25.1 mol.-%. The sizes of the PINs measured by DLS were approximately 203 nm. Internalization into PA was confirmed by confocal microscopy and flow cytometry. Antimicrobial activity of PIN-internalized probiotics encapsulated into ACA MCs was measured by co-culture antimicrobial assays on SG. PIN-internalized probiotics had a higher antimicrobial ability than that of ACA MCs loaded with PA/inulin or PA. Interestingly, when PINs were treated with PA and encapsulated into ACA MCs, as a natural antimicrobial peptide, pediocin was produced much more in the culture medium compared with other groups inulin-loaded ACA MCs and PA-encapsulated into ACA MCs.

Inhibition of Methicillin Resistant Staphylococcus aureus by Bacteriocin Producing Pseudomonas aeruginosa

Bacteriocins are natural antimicrobial peptides with attractive possible applications in food preservation and health care. In the present study, bacteriocin producing bacterial strain Pseudomonas aeruginosa were isolated from soil which exhibited antagonistic activity against Methicillin Resistant Staphylococcus aureus (MRSA) bacteria. The bacteriocin producing strain TA6 was confirmed as P. aeruginosa by biochemical tests and 16S rRNA gene sequence analysis. Maximum bacteriocin activity (100 AU ml−1) was observed at 37 °C with pH 6.0 in 24 h time duration. SDS–PAGE analysis of the extracellular protein of P. aeruginosa TA6 revealed a bacteriocin-like protein with a molecular mass of ~10 kDa. MRSA cells were treated with culture supernatant of P. aeruginosa TA6 and analyzed by FT-IR. The treated and untreated MRSA showed band variations at 671 and 3460 cm−1 corresponding to alkyl and amide group respectively. Mixed proportions of dead and live control populations were analyzed by flow cytometry to determine detection limits of the Dead/Live cells. The flow cytometry detection of defined proportions of dead (p2) and live (p1) cells at 3 h were p2 = 60.5%; p1 = 39.5% and 6 h p2 = 66.5%; p1 = 33.5% respectively. The scanning electron microscopy observation showed the main changes in the cell membrane structural integrity of S. aureus after exposure to the bacteriocin from P. aeruginosa TA6 at 12 h incubation. Together, the results suggested that bacteriocin from P. aeruginosa TA6 was effective against MRSA.

Antibacterial activities and molecular mechanism of amino-terminal fragments from pig nematode antimicrobial peptide CP-1.

High manufacturing costs and weak cell selectivity have limited the clinical application of naturally occurring peptides when faced with an outbreak of drug resistance. To overcome these limitations, a set of antimicrobial peptides was synthesized with the general sequence of (WL)n, where n=1, 2, 3, and WL was truncated from the N-terminus of Cecropin P1 without initial serine residues. The antimicrobial peptide WL3 exhibited stronger antimicrobial activity against both Gram-negative and Gram-positive microbes than the parental peptide CP-1. WL3 showed no hemolysis even at the highest test concentrations compared to the parental peptide CP-1. The condition sensitivity assays (salts, serum, and trypsin) demonstrated that WL3 had high stability in vitro. Fluorescence spectroscopy and electron microscopy indicated that WL3 killed microbes by means of penetrating the membrane and causing cell lysis. In a mouse model, WL3 was able to significantly reduce the bacteria load in major organs and cytokines (TNF-α, IL-6, and IL-1β) levels in serum. In summary, these findings suggest that WL3, which was modified from a natural antimicrobial peptide, has enormous potential for application as a novel antibacterial agent.

ANTIMICROBIAL ACTIVITY OF LIPOPEPTIDES

Abstract The constantly growing number of multidrug-resistant bacterial strains prompts the search for alternative treatments. Synthetic peptides based on natural antimicrobial peptides, also known as antimicrobial lipopeptides, can become a promising group of “drugs” to fight multi-resistant bacteria. The present paper discusses the origins of synthetic lipopeptides, their classification and antimicrobial properties. 1. Introduction. 2. Antimicrobial peptides. 3. Classification of antimicrobial peptides. 4. Lipopeptide antibiotics. 5. Synthetic lipopeptides. 5.1. Ultrashort lipopeptides. 5.2. Peptidomimetics. 5.3. Multivalent lipopeptides. 5.4. Hydrocarbon-stapled lipopeptides. 5.5. Antimicrobial lipopeptides in laboratory researches. 6. Summary

Vitamin D or Flu Vaccine-Benefits over Adverse Effects

Available data suggests that calcitriol has a role in controlling pulmonary inflammation by inducing the production of natural broad-spectrum antimicrobial peptides, the so-called cathelicidin. Randomized clinical studies reported that vitamin D supplements in a daily-wise manner caused a significant risk reduction in acute respiratory tract viral infections and participants who were given vitamin D supplementations were half less infected with flu than those who were not given the vitamin. Hence, vitamin D3 supplementation may be advantageous when compared with flu vaccine especially when we put in consideration morbidities and complications caused by this vaccine as well as the conditions in which influenza vaccine may be contraindicated like in patients who receive cancer immunotherapies targeting the programmed death-ligand 1 (PD-L1) or its receptor, programmed cell death protein 1 (PD-1).

Identification of natural antimicrobial peptides from bacteria through metagenomic and metatranscriptomic analysis of high-throughput transcriptome data of Taiwanese oolong teas

BackgroundAnti-microbial peptides (AMPs), naturally encoded by genes and generally containing 12–100 amino acids, are crucial components of the innate immune system and can protect the host from various pathogenic bacteria and viruses. In recent years, the widespread use of antibiotics has resulted in the rapid growth of antibiotic-resistant microorganisms that often induce critical infection and pathogenesis. Recently, the advent of high-throughput technologies has led molecular biology into a data surge in both the amount and scope of data. For instance, next-generation sequencing technology has been applied to generate large-scale sequencing reads from foods, water, soil, air, and specimens to identify microbiota and their functions based on metagenomics and metatranscriptomics, respectively. In addition, oolong tea is partially fermented and is the most widely produced tea in Taiwan. Many studies have shown the benefits of oolong tea in inhibiting obesity, reducing dental plaque deposition, antagonizing allergic immune responses, and alleviating the effects of aging. However, the microbes and their functions present in oolong tea remain unknown.ResultsTo understand the relationship between Taiwanese oolong teas and bacterial communities, we designed a novel bioinformatics scheme to identify AMPs and their functional types based on metagenomics and metatranscriptomic analysis of high-throughput transcriptome data. Four types of oolong teas (Dayuling tea, Alishan tea, Jinxuan tea, and Oriental Beauty tea) were subjected to 16S ribosomal DNA and total RNA extraction and sequencing. Metagenomics analysis results revealed that Oriental Beauty tea exhibited greater bacterial diversity than other teas. The most common bacterial families across all tea types were Bacteroidaceae (21.7%), Veillonellaceae (22%), and Fusobacteriaceae (12.3%). Metatranscriptomics analysis results revealed that the dominant bacteria species across all tea types were Escherichia coli, Bacillus subtilis, and Chryseobacterium sp. StRB126, which were subjected to further functional analysis. A total of 8194 (6.5%), 26,220 (6.1%), 5703 (5.8%), and 106,183 (7.8%) reads could be mapped to AMPs.ConclusionWe found that the distribution of anti-gram-positive and anti-gram-negative AMPs is highly correlated with the distribution of gram-positive and gram-negative bacteria in Taiwanese oolong tea samples.

Identification and target-modifications of temporin-PE: A novel antimicrobial peptide in the defensive skin secretions of the edible frog, Pelophylax kl. esculentus

A potent natural antimicrobial peptide named temporin-PE was identified and encoded from the skin secretions of Pelophylax kl. esculentus via “shotgun” cloning and LC-MS/MS fragmentation analysis. Target-modifications were carried out to further enhance the antimicrobial and anti-proliferative bioactivities, whilst decreasing the hemolytic effect. A range of bioassays demonstrated that replacing a proline with a tyrosine residue resulted in a loss of the bioactivity against Gram-negative bacteria, but dramatically improved the hemolytic and anti-proliferative activity, indicating the FLP- motif influences the hemolytic activity of temporins. Moreover, the coupling of TAT to the peptide dramatically improved its antimicrobial activity, indicating coupling TAT to these peptides could be considered as a potential tool to improve their antimicrobial activity. Overall, we have shown that targeted modifications of this natural antimicrobial peptide can adjust its bioactivities to help its development as an antibiotic or anti-proliferative agent.

Antimicrobial activity and stability of stapled helices of polybia-MP1.

Polybia-MP1 is a well-known natural antimicrobial peptide isolated from the venom of the social wasp Polybia paulista. A recent study showed that this peptide displays a broad antibacterial spectrum as well as low toxicity to human red blood cells and normal fibroblasts. However, its moderate antimicrobial activity and high susceptibility to protease have been a major hurdle for clinical use. This study examined the possibility of developing biologically more potent, yet metabolically more stable, analogues of MP1 using an emerging technology termed "all-hydrocarbon stapling." The stapled analogues of MP1 showed more than a threefold increase in helicity as well as an approximately 70-fold enhancement in proteolytic stability. These stapled analogues also exhibited a significant increase in inhibition against some Gram-positive bacteria while displaying a modest enhancement in hemolytic activity. Overall, the current study demonstrated that the all-hydrocarbon stapling system is a highly useful tool for the development of biologically more potent and metabolically more stable analogues of natural antimicrobial peptides.

THE IMPORTANCE OF THE FUNCTIONAL STATE OF THIOL-DISULFIDE UNIT OF THE ANTIOXIDANT SYSTEM IN THE ACUTE BACTERIAL DYSENTERY IN THE FORECAST OF THE COURSE AND THE SELECTION OF THE TREATMENT REGIMEN

The goal was to optimize the treatment of shigellosis patients on the basis of an evaluation of the functional state of the thiol-disulfide unit of the antioxidant system (AOS) on a background of various treatment methods. Materials and methods. 400 patients with acute bacterial dysentery of varying severity of the course were observed; Shigella Flexner was isolated in 324(81%) cases, Shigella Sonne - in 76(19%) cases. The determination of sulfhydryl (SH-) groups and disulfide bonds (SS-) was carried out by the direct and reverse amperometric titration with the use of silver nitrate and unithiol in hemolysate. Three groups separated by random sampling were considered. In group I (122 patients), basic therapy was prescribed, including etiotropic and pathogenetic treatment. In group II (134 patients), pathogenetic treatment was prescribed in the combination with a complex of natural cytokines and antimicrobial peptides secreted by pig peripheral blood leukocytesa (»superlimph» preparation). In the third group (144 patients), the drug «superlimph» was prescribed along with etiotropic and pathogenetic treatment. Results. In acute bacterial dysentery disturbances of the redox balance were established to be correlated with the severity of the course in the form of a significant decrease in the level of SH-groups and the thiol-disulfide coefficient on the background of an increase in the level of SS-groups, which indicates to a decrease in the buffer capacity of the AOS. These data can serve as predictors of the nature of the course of dysentery. Comparative clinical evaluation of the effectiveness of various treatment methods revealed the most pronounced in severe disease advantages of complex therapy, including a combination of basic etiotropic, pathogenetic treatment with a complex of natural cytokines and antimicrobial peptides («superlimph»). Conclusion. The change in the ratio of oxidative processes to AOS occurs at any severity of dysentery, but in severe cases these changes acquire a qualitative character. In the survey standards for bacterial dysentery there is recommended to include the determination of indices of the thiol-disulfide unit, as an additional criterion for the severity of the course and the prognosis of the course of the disease. Exceeding the concentration of SS-groups of the concentration of SH-groups and the inversion of the thiol-disulfide coefficient as markers of the breakdown in AOS seem to be prognostically unfavorable factor. The severe course of acute bacterial dysentery is an indication for inclusion of antioxidant agents in the therapeutic complex. Based on the mechanism of revealed abnormalities in AOS, the use of a complex of natural cytokines and antimicrobial peptides («superlimph») can be considered as an immunocorrecting drug.

The synthetic human beta-defensin-3 C15 peptide exhibits antimicrobial activity against Streptococcus mutans, both alone and in combination with dental disinfectants.

Streptococcus mutans is a major etiologic agent of human dental caries that forms biofilms on hard tissues in the human oral cavity, such as tooth and dentinal surfaces. Human β-defensin-3 (HBD3) is a 45-amino-acid natural antimicrobial peptide that has broad spectrum antimicrobial activity against bacteria and fungi. A synthetic peptide consisting of the C-terminal 15 amino acids of HBD3 (HBD3-C15) was recently shown to be sufficient for its antimicrobial activity. Thus, clinical applications of this peptide have garnered attention. In this study, we investigated whether HBD3-C15 inhibits the growth of the representative cariogenic pathogen Streptococcus mutans and its biofilm formation. HBD3-C15 inhibited bacterial growth, exhibited bactericidal activity, and attenuated bacterial biofilm formation in a dose-dependent manner. HBD3-C15 potentiated the bactericidal and anti-biofilm activity of calcium hydroxide (CH) and chlorhexidine digluconate (CHX), which are representative disinfectants used in dental clinics, against S. mutans. Moreover, HBD3-C15 showed antimicrobial activity by inhibiting biofilm formation by S. mutans and other dentinophilic bacteria such as Enterococcus faecalis and Streptococcus gordonii, which are associated with dental caries and endodontic infection, on human dentin slices. These effects were observed for HBD3-C15 alone and for HBD3-C15 in combination with CH or CHX. Therefore, we suggest that HBD3-C15 is a potential alternative or additive disinfectant that can be used for the treatment of oral infectious diseases, including dental caries and endodontic infections.

Highly efficient antibacterial diblock copolypeptides based on lysine and phenylalanine.

A series of amphiphilic diblock copolypeptides (K30 -b-F15 , K30 -b-F30 , and K30 -b-F45 ) were synthesized via N-carboxy-α-amino-anhydride ring-opening polymerization. The copolypeptides had excellent antibacterial efficacy to both Gram positive (S. aureus) and Gram negative (E. coli) bacteria. The minimum inhibitory concentrations (MICs) against E. coli and S. aureus are 8μgmL-1 and 2μgmL-1 , respectively, lower than most natural and artificial antimicrobial peptides (AMPs). The morphological changes of the bacteria treated with diblock copolypeptides were investigated by transmission electron microscopy; the results proved that the diblock copolypeptides had a similar antibacterial pore-forming mechanism to natural cationic peptides. This was confirmed by laser scanning confocal microscope images. CCK-8 results and the MICs showed that the diblock copolypeptides have high selectivity to bacteria, which suggested that the diblock copolypeptides could be excellent candidates to replace traditional antibiotics in future.

Comparative in vitro study on cytotoxicity of recombinant β-hairpin peptides.

Natural antimicrobial peptides (AMPs) are important components of the innate immune system with a wide spectrum of biological activity. In this study, we investigated the cytotoxic effect of three recombinant β-hairpin cationic AMPs: arenicin-1 from the polychaeta Arenicola marina, tachyplesin I from the horseshoe crab Tachypleus tridentatus, and gomesin from the spider Acanthoscurria gomesiana. All the three β-hairpin AMPs were overexpressed in Escherichia coli. Different cell lines were incubated with various concentrations of the investigated AMPs in order to evaluate their cytotoxic activity. Double staining with subsequent flow cytometric analysis was used to determine the predominant way of cell death mediated by each AMP. Hemolytic activity of the peptides was tested against fresh human red blood cells. Our results indicated that all the three AMPs exhibited significant cytotoxic effect against cancer cells that varied depending on the cell line type and, in most cases, on the presence of serum components. Flow cytometric analysis implicitly indicated that tachyplesin I mostly promoted late apoptosis/necrosis, while arenicin-1 and gomesin induced early apoptosis under the same conditions. Tachyplesin I proved to be the most promising therapeutic candidate as it displayed the highest specific cytotoxicity against cancer cell lines, independent of the serum presence.

The role of natural antimicrobial peptides during infection and chronic inflammation.

Natural antimicrobial peptides (AMPs), a family of small polypeptides that are produced by constitutive or inducible expression in organisms, are integral components of the host innate immune system. In addition to their broad-spectrum antibacterial activity, natural AMPs also have many biological activities against fungi, viruses and parasites. Natural AMPs exert multiple immunomodulatory roles that may predominate under physiological conditions where they lose their microbicidal properties in serum and tissue environments. Increased drug resistance among microorganisms is occurring far more quickly than the discovery of new antibiotics. Natural AMPs have shown promise as 'next generation antibiotics' due to their broad-spectrum curative effects, low toxicity, the fact that they are not residual in animals, and the low rates of resistance exhibited by many pathogens. Many types of synthetic AMPs are currently being tested in clinical trials for the prevention and treatment of various diseases such as chemotherapy-associated infections, diabetic foot ulcers, catheter-related infections, and other conditions. Here, we provide an overview of the types and functions of natural AMPs and their role in combating microorganisms and different infectious and inflammatory diseases.

Natural Antimicrobial Peptides as Inspiration for Design of a New Generation Antifungal Compounds.

Invasive fungal infections are associated with high mortality rates, despite appropriate antifungal therapy. Limited therapeutic options, resistance development and the high mortality of invasive fungal infections brought about more concern triggering the search for new compounds capable of interfering with fungal viability and virulence. In this context, peptides gained attention as promising candidates for the antimycotics development. Variety of structural and functional characteristics identified for various natural antifungal peptides makes them excellent starting points for design novel drug candidates. Current review provides a brief overview of natural and synthetic antifungal peptides.

How proteases from Enterococcus faecalis contribute to its resistance to short α-helical antimicrobial peptides.

HYL-20 (GILSSLWKKLKKIIAK-NH2) is an analogue of a natural antimicrobial peptide (AMP) previously isolated from the venom of wild bee. We examined its antimicrobial activity against three strains of Enterococcus faecalis while focusing on its susceptibility to proteolytic degradation by two known proteases-gelatinase (GelE) and serine protease (SprE)-which are secreted by these bacterial strains. We found that HYL-20 was primarily deamidated at its C-terminal which made the peptide susceptible to consecutive intramolecular cleavage by GelE. Further study utilising 1,10-phenanthroline, a specific GelE inhibitor and analogous peptide with D-Lys at its C-terminus (HYL-20k) revealed that the C-terminal deamidation of HYL-20 is attributed to not yet unidentified protease which also cleaves internal peptide bonds of AMPs. In contrast to published data, participation of SprE in the protective mechanism of E. faecalis against AMPs was not proved. The resistance of HYL-20k to C-terminal deamidation and subsequent intramolecular cleavage has resulted in increased antimicrobial activity against E. faecalis grown in planktonic and biofilm form when compared to HYL-20.

Improving nitrogen source utilization from defatted soybean meal for nisin production by enhancing proteolytic function of Lactococcus lactis F44

Nisin, one kind of natural antimicrobial peptide, is produced by certain Lactococcus lactis strains, which generally require expensive high-quality nitrogen sources due to limited ability of amino acids biosynthesis. Here we use defatted soybean meal (DSM) as sole nitrogen source to support L. lactis growth and nisin production. DSM medium composition and fermentation conditions were optimized using the methods of Plackett-Burman design and central composite design. The highest nisin production of 3879.58 IU/ml was obtained in DSM medium, which was 21.3% higher than that of commercial medium. To further increase the utilization ability of nitrogen sources, we enhanced the proteolytic function in L. lactis through rationally expressing the related enzymes, which were selected according to the compositions of amino acids and molecular weight of peptides in DSM medium. Significantly, an artificial proteolytic system consisting of a heterologous protease (NprB), an oligopeptides transporter subunit (OppA) and two peptidases (PepF and PepM) was introduced into L.lactis. The constructed strain BAFM was capable of achieving efficient biomass accumulation and nisin yield with 30% decreased amount of DSM hydrolysates, which further reduced the cost of nisin production. The strategy described here offers opportunities for low-cost L. lactis fermentation and large-scale nisin production in industry.

Abstract 2124: Differentiation of myeloid and multiple myeloma cell lines by inecalcitol involves a marked decrease in CD44 and CD49d cell surface labeling

Abstract Inecalcitol is a vitamin D receptor (VDR) agonist characterized by a high antiproliferative activity on various cancer cell lines (Okamoto et al., 2012; Ma et al., 2013) and a low calcemic potential as demonstrated by the high maximal tolerated oral daily dose of 4 mg in human patients (Medioni et al., 2014). On myeloid cells, inhibition of proliferation by vitamin D derivatives is paralleled by induction of differentiation into a monocyte/macrophage phenotype, mostly described as gain of functions (increase in lysozyme activity, phagocytosis and cell motility; Abe et al., 1981) and of the cell surface CD11b and CD14 biomarkers. The stimulation of the secretion of cathelicidin, a natural human antimicrobial peptide, is another specific activity of vitamin D and its derivatives (Wang et al., 2004). During a screening of 48 CD biomarkers on 4 human myeloid cell lines (HL-60, U-937, MOLM-13 and THP1) and 4 human multiple myeloma cell lines (MM.1R, MM.1S, L-363 and RPMI-8226) treated for 72 hours at 10 nM, we recently discovered that inecalcitol reproducibly induces CD38 expression (Benjamin et al., 2016), another gain of function. We now report the decrease in CD44 and CD49d cell surface labeling in all 8 cell lines (except CD44 in L-363 cells). This loss of functions reached -60% to -70% in MOLM-13 and HL-60 cells. We have then determined the EC50 (mean ± SEM; n = 3 or 4) of inecalcitol for several differentiation parameters on HL-60 cells. The most sensitive gains or loss of functions were the secretion of cathelicidin (0.2 ± 0.1 nM), the induction of CD38 (0.3 ± 0.1 nM) and the decrease in CD44 (0.8 ± 0.4 nM). Inhibition of proliferation (1.9 ± 0.8 nM) was exactly parallel to induction of CD11b (1.8 ± 0.8 nM). Decrease in CD49d (6.6 ± 1.1 nM) and increase in CD14 (8.0 ± 0.5 nM) occurred as final markers of differentiation by inecalcitol. CD44 is the receptor for hyaluronic acid; it is found on the surface of acute myeloid leukemia stem cells and suspected to favor the spread and relapse of the disease. CD49d is the integrin α4-subunit involved in the interactions of tumor cells with their microenvironment resulting in their “hiding” and survival. Therefore, decreasing both CD44 and CD49d represents newly identified potential beneficial pro-differentiation effects of inecalcitol. Citation Format: Susan Benjamin, Cecile Planquette, Remi Delansorne. Differentiation of myeloid and multiple myeloma cell lines by inecalcitol involves a marked decrease in CD44 and CD49d cell surface labeling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2124. doi:10.1158/1538-7445.AM2017-2124

Current state of a dual behaviour of antimicrobial peptides-Therapeutic agents and promising delivery vectors.

Micro-organism resistance is an important challenge in modern medicine due to the global uncontrolled use of antibiotics. Natural and synthetic antimicrobial peptides (AMPs) symbolize a new family of antibiotics, which have stimulated research and clinical interest as new therapeutic options for infections. They represent one of the most promising antimicrobial substances, due to their broad spectrum of biological activity, against bacteria, fungi, protozoa, viruses, yeast and even tumour cells. Besides, being antimicrobial, AMPs have been shown to bind and neutralize bacterial endotoxins, as well as possess immunomodulatory, anti-inflammatory, wound-healing, angiogenic and antitumour properties. In contrast to conventional antibiotics, which have very defined and specific molecular targets, host cationic peptides show varying, complex and very rapid mechanisms of actions that make it difficult to form an effective antimicrobial defence. Importantly, AMPs display their antimicrobial activity at micromolar concentrations or less. To do this, many peptide-based drugs are commercially available for the treatment of numerous diseases, such as hepatitis C, myeloma, skin infections and diabetes. Herein, we present an overview of the general mechanism of AMPs action, along with recent developments regarding carriers of AMPs and their potential applications in medical fields.