Antimicrobial peptides (AMps) are promising alternatives to classical antibiotics for the treatment of drug-resistant infections. Due to their versatility and unlimited sequence space, AMps can be rationally designed by modulating physicochemical determinants to favor desired biological parameters and turned into novel therapeutics. in this study, we utilized key structural and physicochemical parameters, in combination with rational engineering, to design novel short α-helical hybrid peptides inspired by the well-known natural peptides, cathelicidin and aurein. By comparing homologous sequences and abstracting the conserved residue type, sequence templates of cathelicidin (P0) and aurein (A0) were obtained. Two peptide derivatives, P7 and A3, were generated by amino acid substitution based on their residue composition and distribution. in order to enhance antimicrobial activity, a hybrid analog of P7A3 was designed. The results demonstrated that P7A3 had higher antibacterial activity than the parental peptides with unexpectedly high hemolytic activity. Strikingly, c-terminal truncation of hybrid peptides containing only the α-helical segment (PA-18) and shorter derivatives confer potent antimicrobial activity with reduced hemolytic activity in a length-dependent manner. Among all, PA-13, showed remarkable broad-spectrum antibacterial activity, especially against Pseudomonas aeruginosa with no toxicity. PA-13 maintained antimicrobial activity in the presence of physiological salts and displayed rapid binding and penetration activity which resulted in membrane depolarization and permeabilization. Moreover, PA-13 showed an anti-inflammatory response via lipopolysaccharide (LpS) neutralization with dose-dependent, inhibiting, LpS-mediated toll-like receptor activation. this study revealed the therapeutic potency of a novel hybrid peptide, and supports the use of rational design in development of new antibacterial agents. The increasing emergence and dissemination of antibiotic resistance among bacterial pathogens has become a global public health challenge 1,2. Therefore, there is an urgent need to develop new antimicrobial agents to overcome this problem. Antimicrobial peptides (AMPs) are an essential component of the innate immune system produced as a first line of defense by all multicellular organisms 3. With such exceptional properties as broad-spectrum antimicrobial activity, rapid action and infrequent development of resistance 4,5 , AMP-based pharmaceuticals provide excellent templates for a wide range of antimicrobial agents and biomedical applications. In general, naturally occurring AMPs are between 12 and 50 amino acids in length, and often contain cationic and hydrophobic residues 6. Previous studies contributing to the understanding of the structure-activity relationship of AMPs show that one important class of membrane-active AMPs infers an amphipathic α-helical conformation 4,7,8. The initial electrostatic interaction between a positively-charged AMP and the negatively-charged

BackgroundSchistosoma mekongi is one of five major causative agents of human schistosomiasis and is endemic to communities along the Mekong River in southern Lao People’s Democratic Republic (Laos) and northern Cambodia. Sporadic cases of schistosomiasis have been reported in travelers and immigrants who have visited endemic areas. Schistosoma mekongi biology and molecular biology is poorly understood, and few S. mekongi gene and transcript sequences are available in public databases.ResultsTranscriptome sequencing (RNA-Seq) of male and female S. mekongi adult worms (a total of three biological replicates for each sex) were analyzed and the results demonstrated that approximately 304.9 and 363.3 million high-quality clean reads with quality Q30 (> 90%) were obtained from male and female adult worms, respectively. A total of 119,604 contigs were assembled with an average length of 1273 nt and an N50 of 2017 nt. From the contigs, 20,798 annotated protein sequences and 48,256 annotated transcript sequences were obtained using BLASTP and BLASTX searches against the UniProt Trematoda database. A total of 4658 and 3509 transcripts were predominantly expressed in male and female worms, respectively. Male-biased transcripts were mostly involved in structural organization while female-biased transcripts were typically involved in cell differentiation and egg production. Interestingly, pathway enrichment analysis suggested that genes involved in the phosphatidylinositol signaling pathway may play important roles in the cellular processes and reproductive systems of S. mekongi worms.ConclusionsWe present comparative transcriptomic analyses of male and female S. mekongi adult worms, which provide a global view of the S. mekongi transcriptome as well as insights into differentially-expressed genes associated with each sex. This work provides valuable information and sequence resources for future studies of gene function and for ongoing whole genome sequencing efforts in S. mekongi.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-3086-z) contains supplementary material, which is available to authorized users.

Trichinella spiralis can modulate host immune responses to retain a suitable environment for its long-term survival. Incidentally, the parasite elicits regulatory effects through immunomodulatory molecule release, which can suppress host inflammation and may be used for the treatment of unrelated inflammatory diseases in someday. Here we identified and characterized a novel T. spiralis cystatin (TsCstN), which inhibits inflammation mediated by LPS-treated macrophages.Proteins contained in the excretory-secretory (ES) product of muscle-stage T. spiralis (ES-L1) were fractionated, and each was treated with mouse bone marrow-derived macrophages (mBMDMs) before LPS stimulation. The fractions that exhibited high immunomodulatory property by decreasing pro-inflammatory cytokines or increasing anti-inflammatory cytokines were identified by mass spectrometry. Incidentally, the conserved hypothetical protein (Tsp_04814) was selected for further characterization as it presented the most significant MS score. An annotation of Tsp_04814 using protein structural homology comparison suggested that it has high structural similarity to human cystatin E/M (TM score 0.690). The recombinant T. spiralis novel cystatin (rTsCstN) was expressed in Escherichia coli at a molecular weight of approximately 13 kDa. Mouse anti-rTsCstN polyclonal antibody (pAb) could detect native TsCstN in crude worm antigens (CWA) and ES-L1 and be predominantly localized in the stichosome and subcuticular cells. rTsCstN inhibited cysteine proteases in vitro, especially cathepsin L, at an optimal pH of 6. Besides, rTsCstN could be internalized into mBMDMs, which were mostly distributed in the cytoplasm and lysosome both before and after LPS stimulation. To evaluate the rTsCstN immunomodulatory properties on mBMDMs, rTsCstN was incubated with mBMDM before LPS stimulation; this demonstrated that rTsCstN suppressed pro-inflammatory cytokine production and MHC class II expression.T. spiralis L1-derived TsCstN was characterized as a novel cysteine PLOS NEGLECTED TROPICAL DISEASES

Background: Under-regulated national borders in Southeast Asia represent potential regions for enhanced parasitic helminth transmission and present barriers to helminthiasis disease control. Methods: Three Thailand border regions close to Myanmar, Laos and Cambodia were surveyed for clinical parasitic helminth disease. In-field microscopy was performed on stools from 567 individuals. Sub-samples were transported to Bangkok for molecular analysis comprising three multiplex qPCR assays. Results: The overall helminth infection prevalence was 17.99% as assessed by Kato-Katz and 24.51% by qPCR. The combined prevalence of the two methods was 28.57%; the most predominant species detected were Opisthorchis viverrini (18.34%), hookworm (6.88%; Ancylostoma spp. and Necator americanus), Ascaris lumbricoides (2.29%) and Trichuris trichiura (1.76%). Conclusions: These data demonstrate the value of molecular diagnostics for determining more precise prevalence levels of helminthiases in Southeast Asia. Availability of such accurate prevalence information will help guide future public health initiatives and highlights the need for more rigorous surveillance and timely intervention in these regions.

Abstract. Recently there have been calls for the eradication of malaria and the elimination of soil-transmitted helminths (STHs). Malaria and STHs overlap in distribution, and STH infections are associated with increased risk for malaria. Indeed, there is evidence that suggests that STH infection may facilitate malaria transmission. Malaria and STH coinfection may exacerbate anemia, especially in pregnant women, leading to worsened child development and more adverse pregnancy outcomes than these diseases would cause on their own. Ivermectin mass drug administration (MDA) to humans for malaria parasite transmission suppression is being investigated as a potential malaria elimination tool. Adding albendazole to ivermectin MDAs would maximize effects against STHs. A proactive, integrated control platform that targets malaria and STHs would be extremely cost-effective and simultaneously reduce human suffering caused by multiple diseases. This paper outlines the benefits of adding albendazole to ivermectin MDAs for malaria parasite transmission suppression.