Abstract
Due to their archaic life style and microbivor behavior, amoebae may represent a source of antimicrobial peptides and proteins. The amoebic protozoon Dictyostelium discoideum has been a model organism in cell biology for decades and has recently also been used for research on host-pathogen interactions and the evolution of innate immunity. In the genome of D. discoideum, genes can be identified that potentially allow the synthesis of a variety of antimicrobial proteins. However, at the protein level only very few antimicrobial proteins have been characterized that may interact directly with bacteria and help in fighting infection of D. discoideum with potential pathogens. Here, we focus on a large group of gene products that structurally belong to the saposin-like protein (SAPLIP) family and which members we named provisionally Apls (amoebapore-like peptides) according to their similarity to a comprehensively studied antimicrobial and cytotoxic pore-forming protein of the protozoan parasite Entamoeba histolytica. We focused on AplD because it is the only Apl gene that is reported to be primarily transcribed further during the multicellular stages such as the mobile slug stage. Upon knock-out (KO) of the gene, aplD− slugs became highly vulnerable to virulent Klebsiella pneumoniae. AplD− slugs harbored bacterial clumps in their interior and were unable to slough off the pathogen in their slime sheath. Re-expression of AplD in aplD− slugs rescued the susceptibility toward K. pneumoniae. The purified recombinant protein rAplD formed pores in liposomes and was also capable of permeabilizing the membrane of live Bacillus megaterium. We propose that the multifarious Apl family of D. discoideum comprises antimicrobial effector polypeptides that are instrumental to interact with bacteria and their phospholipid membranes. The variety of its members would allow a complementary and synergistic action against a variety of microbes, which the amoeba encounters in its environment.
Highlights
Amoebozoa are interesting models to study the early evolution of innate immunity (Leippe, 1999)
Dictyostelium discoideum is a non-pathogenic, unicellular host used for bacterial and fungal risk assessment studies (Cosson et al, 2002; Alibaud et al, 2008; Koller et al, 2016) and the outcomes from such studies remain surprisingly similar to the observations made in animal hosts (Benghezal et al, 2006; Hagedorn et al, 2009)
D. discoideum serves as a versatile system to explore bacterial virulence genes and their mechanisms of action, not much is known about the effector molecules of D. discoideum and their mode of action to defend against pathogens
Summary
Amoebozoa are interesting models to study the early evolution of innate immunity (Leippe, 1999). The Sentinel cells are continuously shed behind in the slime sheath of migrating slugs (Chen et al, 2007) These immune-like phagocytes have recently been reported to possess the capacity to produce extracellular DNA traps around the pathogen/foreign body (Zhang et al, 2016) in a way similar to phagocytes of vertebrates and invertebrates (Brinkmann et al, 2004; Robb et al, 2014). These features make of D. discoideum an even more attractive model to trace back the conserved functions of the innate immune system across evolution from protozoans to metazoans (Chen et al, 2007; Hagedorn et al, 2009; Zhang and Soldati, 2016)
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