References

Lysosomal cysteine proteases more than scavengers. Biochim Biophys Acta 2. Berdowska I. Cysteine proteases as disease markers. Clin Chim Acta 2004 342(1-2) 41-69. 3. WHO. Amoebiasis. Weekly Epidemiological Record. Vol 72. Geneva 1997 97-100. 4. Lejeune M, Rybicka JM, Chadee K. Recent discoveries in the pathogenesis and immune response toward Entamoeba histolytica. Future Microbiol 2009 4 105-118. 5. Haque R, Huston CD, Hughes M et al. Amebiasis. N Engl J Med 2003 348(16)...

Properties Of Toxoplasma Gondii And Its Cathepsins

T. gondii is a ubiquitous apicomplexan parasite that infects a wide range of warm-blooded animals. It is estimated that almost one-third of the human population is infected by this parasite.24 Infection with Toxoplasma can lead to encephalitis, chorioretinitis and congenital birth defects. AIDS and immunocompromised patients are at especially high risk of developing toxoplasmosis. As an obligate intracellular parasite, T. gondii must invade host cells to survive and expand the infection. Unlike...

Saltzer 1999- Reference About Helminthes

Hotez PJ, Molyneux DH, Stillwaggon E et al. Neglected tropical diseases and HIV AIDS. Lancet 2006 2. Robinson M, Dalton JP. Zoonotic helminth infections with particular emphasis on fasciolosis and other trematodes. Philos Trans R Soc B Biol Sci 2009 364 2763-2776. 3. Engels D, Chitsulo L, Montresor A et al. The global epidemiological situation of schistosomiasis and new approaches to control and research. Acta Trop 2002 82 139-146. 4. Gryseels B, Polman K, Clerinx J et al. Human...

Drug Targets

The few drugs that are available to treat kinetoplastid diseases suffer from a variety of problems, including limited efficacy, toxicity, the need for parenteral administration and the establishment of drug resistance.1 New options for safe, effective and orally-administered treatments are urgently needed. Since the first proof-of-principle study in 1993,88 Family C1 peptidases have been validated as drug targets in many parasitic organisms, including kinetoplastids.89-91 At first, the idea...

Staphopain Activity And Its Relevance To Virulence

The elaborate and unusual mechanism of controlling proteolytic activity in S. aureus strongly suggests that extracellular proteases and staphopains in particular, are very important factors for growth and survival. Each step in releasing staphopain activity is strictly regulated, starting at the level of gene transcription, through to preproprotein secretion and folding and finally zymogen activation and control of mature enzyme activity by specific inhibitors. Such complicated mechanisms have...

Biological Roles Of Cruzain

Cruzain is expressed in all life-cycle stages and has been localized to the lysosome, the prelysosomal 'reservasome', the flagellar pocket and to the plasma membrane in both epimastigotes and amastogites.22'30'37-40 In addition to contributing to general protein turnover as well as nutrient processing, cruzain may play a number of additional essential roles. Cruzain's role in invasion was proposed as Fab fragments of antibodies that targeted cruzain markedly reduced the invasion...

Cruzain

In the mid to late 1970s, a number of protease activities, including cysteine protease (CP) activities, were described in crude T. cruzi extracts.7,8 By the 1980s, CPs had been localized to the lysosome and purified to homogeneity from parasite extracts.9-11 The last two decades have seen a progressive increase in the detailed molecular, biochemical, structural and drug-targeting of cruzain as evidenced by the publication output (Fig. 1). The enzyme was originally termed cruzipain as it was the...

The Pathogenic Potential Of S Aureus

Sar System Staphylococcus

Despite the progress in the disciplines of infectious medicine and pharmacology, S. aureus continues to be a major human pathogen. Infections caused by this micro-organism range from superficial lesions, such as wound infections and abscesses, to life-threatening syndromes, including bacteremia, endocarditis, meningitis and osteomyelitis. The increasing prevalence of antibiotic-resistant strains, especially methicillin resistant S. aureus (MRSA) and the emergence of vancomycin resistant S....

Expression And Activation Of S Aureus Extracellular Proteases

Staphylococcal proteolytic enzymes are expressed as preproproteins, with a large propeptide domain. Firstly, signal sequences target the polypeptide chains for translocation across the cell membrane. Subsequently, in the extracellular environment, the proproteins are folded into enzymatically inert zymogens, most likely in the vicinity of the bacterial cell surface. Figure 4. Diagrammatic representation of the posttranslational steps of activation of extracellular proteases of S. aureus. Broken...

Innate Immune Responses

Substantial evidence supports the view that cysteine proteases secreted by a range of pathogens specifically prevent cells of the innate immune response promoting Th1-adaptive immune responses.10,25-27 The mechanisms are varied and depend on the substrate specificity ofthe protease and ofthe location ofthe pathogen within the host. The innate immune system constitutes the first line ofhost defence during infection and plays a crucial role in the early recognition ofinvading pathogens. Unlike...

Peptidases Of Trichobilharzia

Trichobilharzia Spezies

Although members of the genus Trichobilharzia parasitize bird definitive hosts exclusively, their strategies of exploiting enzymatic equipment are, in general, similar to the well described human schistosomes, such as Schistosoma mansoni, S. japonicum Figure 2. Cercaria A and schistosomulum B of Trichobilharzia regenti. PG postacetabular glands stained by lithium carmine . G gut. Photo B taken by Katerina Blazova, MSc. Figure 2. Cercaria A and schistosomulum B of Trichobilharzia regenti. PG...

Modulation Of Cytokine Responses And Nitric Oxide Production

An intrinsic feature ofendogenous and parasite cystatins is the modification ofthe cytokine and nitric oxide NO production of APCs, such as macrophages.5 Thereby, the presence or absence of pro-inflammatory stimuli such as IFN-y and TNF-a or an anti-inflammatory mediator like IL-10 define the modulatory features of cystatins. Stimulation of IFN-y-primed peritoneal macrophages with chicken cystatin drastically increases NO production by a mechanism that is independent of the protease inhibitory...

About The Editors

DALTON is a Canada Research Chair in Infectious Diseases at the Institute of Parasitology, McGill University, Montreal, Canada. He is also a Professor in Biotechnology and Director of McGill's Graduate Program in Biotechnology. Before joining McGill, Dalton was Director of the Institute for the Biotechnology of Infectious Diseases IBID , University of Technology Sydney UTS , Australia. He was awarded the New South Wales Government BioFirst Award in Biotechnology from 2004-2008. Dalton...

The Structural Basis Of Cruzain Inhibition

Cysteinprotease Vinylsulfone

As described above, cruzain is a papain-family cysteine protease that is folded into two domains. One is predominantly alpha-helical and the other consists of extensive antiparallel beta sheet interactions. The active site is found in the cleft at the interface of the two domains and within this cleft is, expectedly, the catalytic triad of residues Cys 25, His159 and Asnra and extended substrate binding sites. Note cruzain numbering adheres to the numbering used in the original cruzain X-ray...

Host Defence And Amoeba Cysteine Proteases

Amoebae CPs are critical in invasion due their ability to dismantle both innate and adaptive host defence mechanisms Figs. 2 and 3 . EhCPs cleave a wide range of host molecules that result in de-polymerization of the mucus layer, destruction of the colonic epithelium with its accompanying tight junctions, inactivation of immunoglobulins and either activation or inactivation of components of the complement cascade. The intestinal mucus layer forms the first line of host defence against enteric...