Identification of New Sphingomyelinases D in Pathogenic Fungi and Other Pathogenic Organisms

Abstract

Sphingomyelinases D (SMases D) or dermonecrotic toxins are well characterized in Loxosceles spider venoms and have been described in some strains of pathogenic microorganisms, such as Corynebacterium sp. After spider bites, the SMase D molecules cause skin necrosis and occasional severe systemic manifestations, such as acute renal failure. In this paper, we identified new SMase D amino acid sequences from various organisms belonging to 24 distinct genera, of which, 19 are new. These SMases D share a conserved active site and a C-terminal motif. We suggest that the C-terminal tail is responsible for stabilizing the entire internal structure of the SMase D Tim barrel and that it can be considered an SMase D hallmark in combination with the amino acid residues from the active site. Most of these enzyme sequences were discovered from fungi and the SMase D activity was experimentally confirmed in the fungus Aspergillus flavus. Because most of these novel SMases D are from organisms that are endowed with pathogenic properties similar to those evoked by these enzymes alone, they might be associated with their pathogenic mechanisms.

Adaptive evolution in the toxicity of a spider’s venom enzymes

“…In addition to the Loxosceles spiders, other members of the family Sicariidae, such as the genus Sicarius , also contain SMases D [ 3 , 10 ]. Similarly, SMase D toxins were also detected in the genera Ixodes and Rhipicephalus , in the family Ixodidae [ 11 ], and as exotoxins produced by certain pathogenic bacteria. For instance, these toxins were produced by Corynebacterium ulcerans and Arcanobacterium haemolyticum, which are pathogens that cause pharyngitis and other human infections, and by Corynebacterium pseudotuberculosis , which causes lymphadenitis in animals but is also pathogenic for humans [ 8 , 12 ].…”

Loxoscelism: Advances and Challenges in the Design of Antibody Fragments with Therapeutic Potential

“…Aiming to better understand this, we have focused on the SMaseD toxins, which play a key role in loxoscelism. These enzymes have been widely studied and characterized regarding their preferential substrates [48,49], structural basis [1,2,50,51], toxicity [5,52], immunogenicity [53,54] and representativeness in the whole venom [55]. SMases D are also designated dermonecrotic toxins as their recombinant forms have shown to reproduce most of the toxic effects observed in loxoscelism, including dermonecrotic lesions and antigenic properties of the venom [5].…”

Spider Bite: A Rare Case of Acute Necrotic Arachnidism with Rapid and Fatal Evolution

“…Phospholipases D are identified as deleterious components of venom involved in noxious activities. This family of enzymes is described as producing choline to generate ceramide-1-phosphate from sphingomyelin (SM), or lysophosphatidic acid from lysophosphatidylcholine, profoundly altering the lateral structure and morphology of the target membrane, since lysophosphatidylcholine also is a substrate for enzymes found in cytoplasmic cell membranes [ 5 ].…”