Abstract

BackgroundTicks are second to mosquitoes as vectors of human arthropod-borne diseases. Ticks rely heavily on antimicrobial peptides (AMPs) to defend against microbes and defensins are major components of innate immunity in ticks.ResultsTwo novel defensin genes, named HlDFS1 and HlDFS2, were identified from a cDNA library of the hard tick Haemaphysalis longicornis collected in southeast China. The peptides encoded by both genes shares typical features of type-2 arthropod defensin superfamily. The expressions of both genes increased in ticks during blood-feeding. The synthetic minimum functional peptides HlDFS1 and HlDFS2 showed broad spectrum antimicrobial activity against various Gram-positive and Gram-negative bacteria. Moreover, HlDFS1 and HlDFS2 exhibit bactericidal activity to some drug resistant bacteria. HlDFS1, but not HlDFS2, showed inhibitory activity against fungus Candida albicans. HlDFS1 and HlDFS2 had no significant hemolysis effect on human erythrocytes at low concentrations and did not impair mammalian cell survival. Finally, HlDFS1 and HlDFS2 significantly protected mice against lethal infection by Staphylococcus aureus and Micrococcus luteus.ConclusionsHlDFS1 and HlDFS2 are two novel functional defensins from the hard tick Haemaphysalis longicornis. They showed bactericidal activity against various Gram-positive and Gram-negative bacteria and significantly protect mice against lethal bacterial infection. Thus, HlDFS1 and HlDFS2 can be introduced to the medical field as new drug candidates with antibacterial activity.

Highlights

  • Ticks are obligate hematophagous ectoparasites, living by feeding on the blood of mammals, birds, and sometimes reptiles and amphibians [1]

  • Haemaphysalis longicornis defensin 1 (HlDFS1) and Haemaphysalis longicornis defensin 2 (HlDFS2) inhibit the growth of antibiotic resistant bacteria As drug resistance is a growing public health concern, we explored the role of HlDFS1 and HlDFS2 on eleven clinical isolated antibiotic resistant bacteria

  • HlDFS1 and HlDFS2 had therapeutic efficacy on mice challenged by lethal bacterial infection

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Summary

Introduction

Ticks are obligate hematophagous ectoparasites, living by feeding on the blood of mammals, birds, and sometimes reptiles and amphibians [1]. Ticks harm people indirectly by transmitting pathogenic organisms, such as protozoa, viruses and bacteria As they are widely distributed around the world, especially in warm, humid climates, ticks occupy the second place, after mosquitoes, in the abundance of transmission of arthropodborne diseases. Defensins are small cysteinerich cationic proteins (usually contain six cysteine residues) forming disulfide bridges with the conserved pairing Cys1Cys, Cys2-Cys, and Cys3-Cys6 [3, 6, 10]. They are usually expressed in the midgut (MG) after blood-feeding and pathogen invasion [11]. Ticks rely heavily on antimicrobial peptides (AMPs) to defend against microbes and defensins are major components of innate immunity in ticks

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