Kinetoplastid Biology and Disease最新文献

This paper is a commentary on "Species concepts for trypanosomes: from morphological to molecular definitions?" by Wendy Gibson published in this journal 1. Taxonomy has been traditionally based on expert opinion which is influenced among other factors by the philosophical and educational background of the expert concerned. This has resulted in widely different criteria for species among the trypanosomatids when compared to the actual genetic diversity involved. Gibson's paper presents an example of this within the trypanosome sub-genera. Although attempts have been made to put taxonomy on a more objective basis expert opinion still appears to dominate in the actual classifications in use.

Members of the Trypanosomatidae family comprises species that are causative of important human diseases such as Chagas'disease, Leishmaniasis and sleeping sickness. A wealth of evidence has accumulated that illustrates the ability of these unicellular organisms to undergo, with or without induction (stress conditions), a cell death with some features resembling apoptosis-like phenomenon. However, despite the apparent phenotypic similarities between the apoptosis-like death of kinetoplastids and mammalian nucleated cell programmed cell death (PCD), the pathways seem to differ significantly. This review analyses some of the current data related to the cell death in trypanosomatids. Special attention is given to members of conserved protein families demonstrating remarkable diversity and plasticity of function [i.e. elongation factor-1 subunits alpha and gamma; and the Silent Information Regulator (SIR2)-related gene, showed to be associated with resistance to apoptosis-like death in Leishmania]. The elucidation of the molecular events which tightly regulated the processes of growth arrest, differentiation and death of Trypanosoma cruzi, Leishmania spp and African trypanosomes, might allow not only to define a more comprehensive view of the cell death machinery in term of evolutionary origin but may also be useful to identify new target molecules for chemotherapeutic drug development and therapeutic intervention.

The protozoan parasites Leishmania, Trypanosoma cruzi and Trypanosoma brucei show multiple features consistent with a form of programmed cell death (PCD). Despite some similarities with apoptosis of mammalian cells, PCD in trypanosomatid protozoans appears to be significantly different. In these unicellular organisms, PCD could represent an altruistic mechanism for the selection of cells, from the parasite population, that are fit to be transmitted to the next host. Alternatively, PCD could help in controlling the population of parasites in the host, thereby increasing host survival and favoring parasite transmission, as proposed by Seed and Wenk. Therefore, PCD in trypanosomatid parasites may represent a pathway involved both in survival and propagation of the species.

It is shown using mouse models that the African trypanosomes exert a significant drain upon their host's carbohydrate (energy) resources; and that the higher the parasitemia, the greater the energy demand. It is, therefore, hypothesized that the long slender (LS) to short stumpy (SS) transition evolved, in part, to help control the parasitemia and to increase host survival time. It is also suggested that the SS population is heterogeneous. One part of the population is tsetse infective, while a second older SS population is undergoing apoptotic-like events, which leads to their cell death and their stimulation of the host's immune response. This immune stimulation by the old dying SS forms would eliminate the major LS and SS variant antigen population, and produce the chronic relapsing infection. It is concluded that the SS stages during the apoptosis-like process are acting altruistically. They give their lives to insure the long-term survival of the host, and to insure renewed growth of the minor LS variants and new infective SS forms. This process is predicted to increase the probability for the successful transmission of the trypanosomes to a new host.

One of the major differences between protozoan differentiation and metazoan differentiation is that protozoan cells normally retain potency during differentiation, which need not, therefore, be considered altruistic. Altruism does, however, arise at the level of the organism and consequently, protozoons have the potential to evolve altruistic traits. This is particularly true when, as with Trypanosoma brucei parasitaemias, populations are genetically homogeneous. This essay argues that whilst reports of altruistic phenomena during the trypanosome life cycle remain controversial, the prospect of reagents able to instigate pathways of cell death or differentiation bears further investigation.

BACKGROUND: The protozoan pathogen, Trypanosoma brucei, undergoes complex cycles of differentiation and multiplication in its vector, the tsetse fly, genus Glossina. Flies are refractory to infection and resistance mechanisms operate at a number of levels and timepoints. Here we have used highly conspicuous green fluorescent trypanosomes to study the early events in establishment of infection in the fly midgut. RESULTS: Less than 10% of the bloodstream form trypanosomes in the infected feed differentiated into viable procyclics. Up to day 3, trypanosomes were found in the bloodmeal in every fly examined, and increased in number between days 1 and 3. Flies dissected on days 5 and 6 fell into 2 clearly distinct groups: those with high numbers of trypanosomes and those with undetectable infection. Trypanosomes were found in the ectoperitrophic space and proventriculus from 6 days following the infective feed. CONCLUSION: Trypanosomes that have undergone successful differentiation appear to experience an environment within the midgut suited to their unrestricted growth for the first 3 days. After this time, a process of attrition is evident in some flies, which leads to the complete elimination of infection. By day 5, flies fall into 2 groups according to the level of infection: high or undetectable. This timecourse coincides with lectin secretion, development of the PM and the digestion and movement of the bloodmeal along the gut. Further experiments are needed to discriminate between these factors.

BACKGROUND: Cutaneous leishmaniasis (CL) is endemic in the Middle Eastern countries. New cases are emerging in areas previously free of the disease. In Jordan, the diagnosis of cases during the 1960s and 1970s was mainly reported in military hospitals in Amman. Endemicity of the disease was ascertained after reporting a total of 524 cases during 1973-1978. RESULTS: Leishmania major and Leishmania tropica were isolated from seventy-six autochthonous and imported cases of CL, during eight-year period. The highest infection rates recorded were in the central part of Jordan (60.5%), in males (72.4%) and in the age group 21-30 years (30.5%). Lesions were on the exposed sites of the body, mainly on the face (40%). Both Leishmania spp. were isolated from all parts of the country, although L. major was the predominant species (75% of cases) in all areas except in the north part of Jordan. Isoenzyme characterization of the isolates identified four previously undescribed zymodemes (Z). Four Leishmania major zymodemes were found, one of which was a new zymodeme (ZMON-103 variant in GLUD220); L. major ZMON-103 was the most common zymodeme. Four Leishmania tropica zymodemes were identified, of which three were previously unreported. Of these, ZMON-54 var PGD96-97 was isolated from autochthonous cases, whereas ZMON-59 var MDH100 and ZMON-75 var FH110 were obtained from both autochthonous and imported cases, or from an imported CL case, respectively. CONCLUSION: The findings of this study indicate the emergence of the CL disease in new areas. New foci are reported, where the sporadic nature of the cases indicates recent spread of the disease to these areas and the urge for the implementation of control measures.

The taxonomic status of Trypanosoma rangeli as well as the tools for its molecular characterization is briefly commented.