scholarly journals A Lesson in Survival, by Giardia lamblia

2010 ◽  
Vol 10 ◽  
pp. 2019-2031 ◽  
Author(s):  
Andrea A. S. Rópolo ◽  
Maria C. Touz
Keyword(s):  
Giardia Lamblia ◽  
Drug Targets ◽  
Antigenic Variation ◽  
Protozoan Parasite ◽  
Arginine Deiminase ◽  
Multiple Roles ◽  
Variation Potential ◽  
Acquired Immune Responses ◽  
The One ◽  
Potential Drug Targets

In the relationships between host and parasites, there is a cross-talk that involves diverse mechanisms developed by two different genetic systems during years of evolution. On the one hand, immunocompetent hosts have developed effective innate and acquired immune responses that are used to restrict or avoid parasitism. On the other hand, parasites evade the immune response, expressing different antigens on their surface or by using other specific mechanisms, such as nutrient depletion. In this review, we analyze the survival mechanisms used by the protozoan parasiteGiardia lambliaduring infection. In particular, we examine the multiple roles played by the enzyme arginine deiminase during colonization of the gut, also involving the parasite's mechanism of antigenic variation. Potential drug targets for the treatment of giardiasis are also discussed.

scholarly journals Experimental Infections of Neonatal Mice with Cysts of Giardia lamblia Clone GS/M-83-H7 Are Associated with an Antigenic Reset of the Parasite

2004 ◽  
Vol 72 (8) ◽  
pp. 4763-4771 ◽  
Author(s):  
N. von Allmen ◽  
M. Bienz ◽  
A. Hemphill ◽  
N. Müller
Keyword(s):  
Giardia Lamblia ◽  
Antigenic Variation ◽  
Early Stage ◽  
Surface Protein ◽  
Protozoan Parasite ◽  
Simultaneous Increase ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Experimental Infections ◽  
Major Surface

ABSTRACT Transmission of the protozoan parasite Giardia lamblia from one to another host individuum occurs through peroral ingestion of cysts which, following excystation in the small intestine, release two trophozoites each. Many studies have focused on the major surface antigen, VSP (for variant surface protein), which is responsible for the antigenic variability of the parasite. By using trophozoites of G. lamblia clone GS/M-83-H7 (expressing VSP H7) and the neonatal mouse model for experimental infections, we quantitatively assessed the process of antigenic variation of the parasite on the transcriptional level. In the present study, variant-specific regions identified on different GS/M-83-H7 vsp sequences served as targets for quantitative reverse transcription-PCR to monitor alterations in vsp mRNA levels during infection. Respective results demonstrated that antigenic switching of both the duodenal trophozoite and the cecal cyst populations was associated with a massive reduction in vsp H7 mRNA levels but not with a simultaneous increase in transcripts of any of the subvariant vsp genes analyzed. Most importantly, we also explored giardial variant-type formation and vsp mRNA levels after infection of mice with cysts. This infection mode led to an antigenic reset of the parasite in that a VSP H7-negative inoculum “converted” into a population of intestinal trophozoites that essentially consisted of the original VSP H7 type. This antigenic reset appears to be associated with excystation rather than with a selective process which favors expansion of a residual population of VSP H7 types within the antigenically diversified cyst inoculum. Based on these findings, the VSP H7 type has to be regarded as a predominant variant of G. lamblia clone GS/M-83-H7 which (re-)emerges during early-stage infection and may contribute to an optimal establishment of the parasite within the intestine of the experimental murine host.

scholarly journals Genomewide Analysis of Mode of Action of the S-Adenosylmethionine Analogue Sinefungin in Leishmania infantum

mSystems ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Arijit Bhattacharya ◽  
Mansi Sharma ◽  
Charles Packianathan ◽  
Barry P. Rosen ◽  
Philippe Leprohon ◽  
...  
Keyword(s):  
Drug Targets ◽  
Protozoan Parasite ◽  
Cell Types ◽  
Biosynthetic Pathways ◽  
Potential Drug ◽  
Pathogenic Parasite ◽  
Potential Drug Targets ◽  
Chemotherapeutic Interventions

The two main cellular metabolic one-carbon donors are reduced folates and S-adenosylmethionine, whose biosynthetic pathways have proven highly effective in chemotherapeutic interventions in various cell types. Sinefungin, a nucleoside analogue of S-adenosylmethionine, was shown to have potent activity against the protozoan parasite Leishmania. Here, we studied resistance to sinefungin using whole-genome approaches as a way to further our understanding of the role of S-adenosylmethionine in this parasite and to reveal novel potential drug targets. These approaches allowed the characterization of novel features related to S-adenosylmethionine function in Leishmania which could further help in the development of sinefungin-like compounds against this pathogenic parasite.

Quantitative assessment of sense and antisense transcripts from genes involved in antigenic variation (vsp genes) and encystation (cwp 1 gene) of Giardia lamblia clone GS/M-83-H7

Parasitology ◽  
2004 ◽  
Vol 130 (4) ◽  
pp. 389-396 ◽  
Author(s):  
N. von ALLMEN ◽  
M. BIENZ ◽  
A. HEMPHILL ◽  
N. MÜLLER
Keyword(s):  
Giardia Lamblia ◽  
Antisense Rna ◽  
Antigenic Variation ◽  
Surface Protein ◽  
Protozoan Parasite ◽  
Relative Distribution ◽  
Intestinal Protozoan ◽  
Rna Molecules ◽  
First Time

Antigenic variation of the intestinal protozoan parasite Giardia lamblia is caused by an exchange of the parasite's variant surface protein (VSP) coat. Many investigations on antigenic variation were performed with G. lamblia clone GS/M-83-H7 which produces surface antigen VSP H7. To generate novel information on giardial vsp gene transcription, vsp RNA levels were assessed by quantitative reverse transcription-(RT)-PCR in both axenic VSP H7-type trophozoites and subvariants obtained after negative selection of GS/M-83-H7 trophozoites by treatment with a cytotoxic, VSP H7-specific monoclonal antibody. Our investigation was not restricted to the assessment of the sense vsp transcript levels but also included an approach aimed at the detection of complementary antisense vsp transcripts within the two trophozoite populations. We found that sense vsp H7 RNA predominated in VSP H7-type trophozoites while sense RNA from only one (vsp IVg) of 8 subvariant vsp genes totally analysed predominated in subvariant-type trophozoites. Interestingly, the two trophozoite populations exhibited a similar relative distribution regarding the vsp H7 and vsp IVg antisense RNA molecules. An analogous sense versus antisense RNA pattern was also observed when the transcripts of gene cwp 1 (encoding cyst wall protein 1) were investigated. Here, both types of RNA molecules only appeared after cwp 1 had been induced through in vitro encystation of the parasite. These findings for the first time demonstrated that giardial antisense RNA production did not occur in a constitutive manner but was directly linked to complementary sense RNA production after activation of the respective gene systems.

scholarly journals Antigenic variation in Giardia lamblia and the host's immune response

1997 ◽  
Vol 352 (1359) ◽  
pp. 1369-1375 ◽  
Author(s):  
Theodore E. Nash
Keyword(s):  
Giardia Lamblia ◽  
Antigenic Variation ◽  
Protozoan Parasite ◽  
Scid Mice ◽  
Surface Proteins ◽  
Mouse Strains ◽  
Post Inoculation ◽  
Immune Pressure ◽  
Selection Of

Giardia lamblia , a protozoan parasite of the small intestine of humans and other animals, undergoes surface antigenic variation. The antigens involved belong to a family of variant–specific surface proteins (VSPs), which are unique, cysteine–rich zinc finger proteins. The patterns of infection in humans and animals fail to show the expected cyclical waves of increasing and decreasing numbers of parasites expressing unique VSPs. Nevertheless, changes in VSP expression occur within the population in vivo owing to selection of VSPs by both immune and non–immune mechanisms. After inoculation of a single G. lamblia clone (able to persist in in the absence of immune pressure) expressing one VSP (greater than 90 per cent) into mice or humans, the original VSP continues to be expressed until 2 weeks post inoculation (p.i.), when many other VSPs gradually replace it. Selection by immune–mediated processes is suggested because switching occurs at the same time that humoral responses are first detected. In most mouse strains, switching also occurs at about two weeks. Almost all trophozoites are eliminated at three weeks (p.i.), but a barely detectable infection persists over months. In neonatal mice, apparent self–cure is delayed until the sixth or seventh week. Antigenic switching does not occur in adult or neonatal SCID mice, but does occur in neonatal nude mice, thus implicating B–cell–mediated mechanisms in immune switching. Not all VSPs are expressed to the same degree in vivo . Some VSPs appear to be preferentially selected whereas others are eliminated on a non–immune basis. In infections in which immunity does not play a role, such as in SCID mice, and during the first week of infection in immunocompetent mice or gerbils, persisting VSPs are preferentially expressed and maintained whereas non–persisting VSPs are replaced within the first week of infection. The purpose of antigenic variation may be presentation of a wide assortment of VSPs to hosts, increasing the chance of a successful initial infection or reinfection. Immune selection of variants comes into play following biological selection.

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