Here we report that trypanosomatid flagellates of the genus Blastocrithidia possess catalase. This enzyme is not phylogenetically related to the previously characterized catalases in other monoxenous trypanosomatids, suggesting that their genes have been acquired independently. Surprisingly, Blastocrithidia catalase is less enzymatically active, compared to its counterpart from Leptomonas pyrrhocoris, posing an intriguing biological question why this gene has been retained in the evolution of trypanosomatids.

• Klíčová slova
• Catalase, Oxygen peroxide, Trypanosomatidae,
• MeSH
• fylogeneze MeSH
• katalasa chemie   genetika   metabolismus   MeSH
• molekulární evoluce MeSH
• peroxid vodíku chemie   metabolismus   MeSH
• protozoální proteiny chemie   genetika   metabolismus   MeSH
• sekvence aminokyselin MeSH
• sekvenční seřazení MeSH
• Trypanosomatina klasifikace   enzymologie   genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• katalasa MeSH
• peroxid vodíku MeSH
• protozoální proteiny MeSH

• Klíčová slova
• CATALASE/urine *,
• MeSH
• katalasa moč   MeSH
• lidé MeSH
• tělesné tekutiny * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• katalasa MeSH

• Klíčová slova
• CATALASE *, CEREBROSPINAL FLUID *,
• MeSH
• katalasa * MeSH
• lidé MeSH
• mozkomíšní mok * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• katalasa * MeSH

• Klíčová slova
• CATALASE/chemistry *, LIVER/chemistry *,
• MeSH
• játra chemie   MeSH
• katalasa chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• katalasa MeSH

Catalase is one of the most abundant enzymes on Earth. It decomposes hydrogen peroxide, thus protecting cells from dangerous reactive oxygen species. The catalase-encoding gene is conspicuously absent from the genome of most representatives of the family Trypanosomatidae. Here, we expressed this protein from the Leishmania mexicana Β-TUBULIN locus using a novel bicistronic expression system, which relies on the 2A peptide of Teschovirus A. We demonstrated that catalase-expressing parasites are severely compromised in their ability to develop in insects, to be transmitted and to infect mice, and to cause clinical manifestation in their mammalian host. Taken together, our data support the hypothesis that the presence of catalase is not compatible with the dixenous life cycle of Leishmania, resulting in loss of this gene from the genome during the evolution of these parasites.

• Klíčová slova
• Leishmania, catalase, dixeny, evolution, virulence,
• MeSH
• faktory virulence genetika   metabolismus   MeSH
• katalasa genetika   metabolismus   MeSH
• kultivované buňky MeSH
• Leishmania mexicana genetika   růst a vývoj   patogenita   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• protozoální proteiny genetika   MeSH
• Psychodidae parazitologie   MeSH
• stadia vývoje genetika   MeSH
• Teschovirus genetika   MeSH
• virulence MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• faktory virulence MeSH
• katalasa MeSH
• protozoální proteiny MeSH

Nearly all aerobic organisms are equipped with catalases, powerful enzymes scavenging hydrogen peroxide and facilitating defense against harmful reactive oxygen species. In trypanosomatids, this enzyme was not present in the common ancestor, yet it had been independently acquired by different lineages of monoxenous trypanosomatids from different bacteria at least three times. This observation posited an obvious question: why was catalase so "sought after" if many trypanosomatid groups do just fine without it? In this work, we analyzed subcellular localization and function of catalase in Leptomonas seymouri. We demonstrated that this enzyme is present in the cytoplasm and a subset of glycosomes, and that its cytoplasmic retention is H2O2-dependent. The ablation of catalase in this parasite is not detrimental in vivo, while its overexpression resulted in a substantially higher parasite load in the experimental infection of Dysdercus peruvianus. We propose that the capacity of studied flagellates to modulate the catalase activity in the midgut of its insect host facilitates their development and protects them from oxidative damage at elevated temperatures.

• Klíčová slova
• Catalase, Hydrogen peroxide, Trypanosomatids,
• MeSH
• cytoplazma MeSH
• katalasa * metabolismus   MeSH
• mikrotělíska metabolismus   MeSH
• peroxid vodíku * metabolismus   MeSH
• Trypanosomatina * enzymologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• katalasa * MeSH
• peroxid vodíku * MeSH

• Klíčová slova
• CATALASE/cerebrospinal fluid *,
• MeSH
• katalasa mozkomíšní mok   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• katalasa MeSH

The catalase gene is a virtually ubiquitous component of the eukaryotic genomes. It is also present in the monoxenous (i.e. parasitizing solely insects) trypanosomatids of the subfamily Leishmaniinae, which have acquired the enzyme by horizontal gene transfer from a bacterium. However, as shown here, the catalase gene was secondarily lost from the genomes of all Leishmania sequenced so far. Due to the potentially key regulatory role of hydrogen peroxide in the inter-stagial transformation of Leishmania spp., this loss seems to be a necessary prerequisite for the emergence of a complex life cycle of these important human pathogens. Hence, in this group of protists, the advantages of keeping catalase were uniquely outweighed by its disadvantages.

• Klíčová slova
• Catalase, Gene loss, Leishmania, Trypanosomatids,
• MeSH
• Bacteria genetika   MeSH
• delece genu * MeSH
• exprese genu MeSH
• fylogeneze MeSH
• genom * MeSH
• houby genetika   MeSH
• interakce hostitele a parazita MeSH
• katalasa genetika   MeSH
• Leishmania účinky léků   genetika   růst a vývoj   metabolismus   MeSH
• lidé MeSH
• peroxid vodíku metabolismus   farmakologie   MeSH
• Psychodidae parazitologie   MeSH
• signální transdukce MeSH
• stadia vývoje účinky léků   genetika   MeSH
• Trypanosomatina klasifikace   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• katalasa MeSH
• peroxid vodíku MeSH

Catalase is a widespread heme-containing enzyme, which converts hydrogen peroxide (H2 O2 ) to water and molecular oxygen, thereby protecting cells from the toxic effects of H2 O2 . Trypanosoma brucei is an aerobic protist, which conspicuously lacks this potent enzyme, present in virtually all organisms exposed to oxidative stress. To uncover the reasons for its absence in T. brucei, we overexpressed different catalases in procyclic and bloodstream stages of the parasite. The heterologous enzymes originated from the related insect-confined trypanosomatid Crithidia fasciculata and the human. While the trypanosomatid enzyme (cCAT) operates at low temperatures, its human homolog (hCAT) is adapted to the warm-blooded environment. Despite the presence of peroxisomal targeting signal in hCAT, both human and C. fasciculata catalases localized to the cytosol of T. brucei. Even though cCAT was efficiently expressed in both life cycle stages, the enzyme was active in the procyclic stage, increasing cell's resistance to the H2 O2 stress, yet its activity was suppressed in the cultured bloodstream stage. Surprisingly, following the expression of hCAT, the ability to establish the T. brucei infection in the tsetse fly midgut was compromised. In the mouse model, hCAT attenuated parasitemia and, consequently, increased the host's survival. Hence, we suggest that the activity of catalase in T. brucei is beneficial in vitro, yet it becomes detrimental for parasite's proliferation in both invertebrate and vertebrate hosts, leading to an inability to carry this, otherwise omnipresent, enzyme.

• Klíčová slova
• catalase, development, hydrogen peroxide, trypanosoma,
• MeSH
• hmyz účinky léků   růst a vývoj   metabolismus   MeSH
• katalasa metabolismus   MeSH
• peroxid vodíku farmakologie   MeSH
• Trypanosoma brucei brucei účinky léků   metabolismus   MeSH
• Trypanosoma účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• katalasa MeSH
• peroxid vodíku MeSH

The development of nanomedicines for the treatment of neurodegenerative disorders demands innovative nanoarchitectures for combined loading of multiple neuroprotective compounds. We report dual-drug loaded monoolein-based liquid crystalline architectures designed for the encapsulation of a therapeutic protein and a small molecule antioxidant. Catalase (CAT) is chosen as a metalloprotein, which provides enzymatic defense against oxidative stress caused by reactive oxygen species (ROS) such as hydrogen peroxide (H2O2). Curcumin (CU), solubilized in fish oil, is co-encapsulated as a chosen drug with multiple therapeutic activities, which may favor neuro-regeneration. The prepared self-assembled biomolecular nanoarchitectures are characterized by biological synchrotron small-angle X-ray scattering (BioSAXS) at multiple compositions of the lipid/co-lipid/water phase diagram. Constant fractions of curcumin (an antioxidant) and a PEGylated agent (TPEG1000) are included with regard to the lipid fraction. Stable cubosome architectures are obtained for several ratios of the lipid ingredients monoolein (MO) and fish oil (FO). The impact of catalase on the structural organization of the cubosome nanocarriers is revealed by the variations of the cubic lattice parameters deduced by BioSAXS. The outcome of the cellular uptake of the dual drug-loaded nanocarriers is assessed by performing a bioassay of catalase peroxidatic activity in lysates of nanoparticle-treated differentiated SH-SY5Y human cells. The obtained results reveal the neuroprotective potential of the in vitro studied cubosomes in terms of enhanced peroxidatic activity of the catalase enzyme, which enables the inhibition of H2O2 accumulation in degenerating neuronal cells.

• Klíčová slova
• BioSAXS, catalase, cubosome, curcumin, fish oil, liquid crystalline nanoparticles, peroxidatic activity of catalase,
• MeSH
• kapalné krystaly chemie   MeSH
• katalasa chemie   MeSH
• kurkumin chemie   MeSH
• lidé MeSH
• maloúhlový rozptyl MeSH
• nanostruktury chemie   MeSH
• peroxid vodíku chemie   MeSH
• polyethylenglykoly chemie   MeSH
• reaktivní formy kyslíku MeSH
• synchrotrony MeSH
• zobrazování trojrozměrné MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• katalasa MeSH
• kurkumin MeSH
• peroxid vodíku MeSH
• polyethylene glycol 1000 MeSH Prohlížeč
• polyethylenglykoly MeSH
• reaktivní formy kyslíku MeSH