Phospholipases a in trypanosomatids

Abstract

Phospholipases are a complex and important group of enzymes widespread in nature, that play crucial roles in diverse biochemical processes and are classified as A(1), A(2), C, and D. Phospholipases A(1) and A(2) activities have been linked to pathogenesis in various microorganisms, and particularly in pathogenic protozoa they have been implicated in cell invasion. Kinetoplastids are a group of flagellated protozoa, including extra- and intracellular parasites that cause severe disease in humans and animals. In the present paper, we will mainly focus on the three most important kinetoplastid human pathogens, Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp., giving a perspective of the research done up to now regarding biochemical, biological, and molecular characteristics of Phospholipases A(1) and A(2) and their contribution to pathogenesis.

Figure 1

Hydrolysis of phospholipids by phospholipases. Arrows indicate the sites of attack for hydrolytic cleavage of phospholipases type A₁, A₂, C, and D. The main products generated by their action are also shown. R1/R2: free fatty acids in sn-1 or sn-2 positions; X: choline, ethanolamine, serine, inositol, and so forth.

Figure 2

Multiple sequence alignment of trypanosome PLA₁. Alignment of the protein sequences of cloned T. brucei, T. cruzi, and L. braziliensis PLA₁ and T. congolense and T. vivax putatives PLA₁ was performed with NTI 10 Software (Invitrogen) using the Clustal W algorithm. The lipase consensus pattern is underlined. Letters indicate: identical (red), conserved (blue), similar (green), weakly similar (grey), and nonsimilar (black) amino acids. Leishmania braziliensis PLA₁ (TriTrypDB LbrM31_V2.2750), Trypanosoma brucei PLA₁ (TriTrypDB Tb.927.1.4830), Trypanosoma congolense putative PLA₁ (TriTrypDB TcIL3000.1.2010), Trypanosoma vivax putative PLA₁ (TriTrypDB TvY486_0102170), and Trypanosoma cruzi PLA₁ (TriTrypDB Tc00.1047053510679.100).