Peptidases in parasitic nematodes: A review

Abstract

The nematodes are, after the insects, the group of organisms with the largest number of species identified. They include members of great medical, veterinary and agricultural significance, making this group one of the most important animal parasites. However there are many gaps in our knowledge of them. For example, there is still not a single nematode species for which we have detailed knowledge of feeding, digestion and nutritional requirements, showing that there are still many aspects to be learned about nutrition in nematodes [1]. Our understanding of the process of protein digestion, a very important function in the biology of any organism, is still poor since our knowledge is composed of fragmentary data for different groups of nematodes. It is believed that peptidases are essential during the development process and in the most critical moments of parasite-host interactions, and are thus directly involved with the growth and survival of the parasite. Their identification and characterization are important for basic understanding of the biology of the parasite, and their relevance to parasitic nematodes as virulence factors is clear. Consequently, peptidases are currently viewed as potential targets for vaccines, drugs and serodiagnosis. Despite this, in most cases, the precise physiological functions of peptidases in parasites are not known [2]. Peptidases comprise a large class of hydrolytic enzymes in parasitic nematodes, participating in nutrition through digestion of host proteins [3]. They also act in the moulting and resorption of the cuticle by processing and activating proenzymes or prohormones [4], degrading proteins that anchor the epidermis to the underlying cuticle (apolysis) [5], or by digesting the cuticle for resorption or facilitating its shedding (ecdysis) [6]. They are also active during embryonic development of the egg [7]. Peptidases are important in host-parasite relationships, being important virulence factors in some parasites [8]. The pathogenicity of several species of nematode has been significantly correlated with their peptidase activity. These include Strongyloides stercoralis [9], Anisakis simplex [10], Onchocerca volvulus [11], Trichinella spiralis [12], and Ancylostoma caninum [13]. All major types of peptidases have been described in nematodes. Aspartic peptidases have been described primarily in functions related to the digestion of nutrients. In invertebrates it is thought that, along with the cysteine peptidases, these have the same role as aspartic and serine peptidases in vertebrates [14]. In parasitic nematodes, the cysteine peptidases may be the class for which we have most information, since, owing to their great diversity, they cover virtually all functions in which peptidases are involved in parasitic nematodes. Cathepsins B and L are types of cysteine peptidases belonging to the papain family, and have been comprehensively studied in nematodes [15]. High variability has been found among the cathepsins B from different species of nematodes regarding optimum temperature and pH, and substrate affinity. It is thought that their main role is to digest nutrients and that the high interspecific variability observed is due to the nematode adapting to the ecological niche it occupies [16]. Cathepsins L also seem to be involved in the digestion of nutrients, as well as in processes of embryogenesis and moulting [2]. Many of these cathepsins L have counterparts in the free living nematode Caenorhabditis elegans, suggesting that they may be involved in conserved functions in different species of nematodes, but little is known about their precise functions [7]. The metallopeptidases are involved in the invasion of host tissues by the parasite, as they are able to degrade the extracellular matrix, and are also involved in the process of ecdysis and digestion of nutrients. The serine peptidases are also present in nematodes, and, along with the metallopeptidases, are believed to play the largest part in the invasion of host tissues by the parasites [10].