Jaburetox: update on a urease-derived peptide

Abstract

Urease from Canavalia ensiformis seeds was the first enzyme ever to be crystallized, in 1926. These proteins, found in plants, bacteria and fungi, present different biological properties including catalytic hydrolysis of urea, and also enzyme-independent activities, such as induction of exocytosis, pro-inflammatory effects, neurotoxicity, antifungal and insecticidal properties. Urease is toxic to insects and fungi per se but part of this toxicity relies on an internal peptide (~11 kDa), which is released upon digestion of the protein by insect enzymes. A recombinant form of this peptide, called jaburetox (JBTX), was constructed using jbureII gene as a template. The peptide exhibits liposome disruption properties, and insecticidal and fungicidal activities. Here we review the known biological properties activities of JBTX, and comment on new ones not yet fully characterized. JBTX was able to cause mortality of Aedes aegypti larvae in a feeding assay whereas in a dose as low as of 0.1 μg it provoked death of Triatoma infestans bugs. JBTX (10−5–10−6 M) inhibits the growth of E. coli, P. aeruginosa and B. cereus after 24 h incubation. Multilamellar liposomes interacting with JBTX undergo reorganization of the membrane’s lipids as detected by small angle X-ray scattering (SAXS) studies. Encapsulating JBTX into lipid nanoparticles led to an increase of the peptide’s antifungal activity. Transgenic tobacco and sugarcane plants expressing the insecticidal peptide JBTX, showed increased resistance to attack of the insect pests Spodoptera frugiperda, Diatraea saccharalis and Telchin licus licus. Many questions remain unanswered; however, so far, JBTX has shown to be a versatile peptide that can be used against various insect and fungus species, and in new bacterial control strategies.

Jaburetox, a urease‐derived peptide: Effects on enzymatic pathways of the cockroach Nauphoeta cinerea

“…On the contrary, when R. prolixus and T. infestans were tested under similar doses, the triatomines had 100% of mortality after 72 hr or less (Fruttero et al, 2016; Galvani et al, 2015), confirming that they are susceptible to the Jbtx effects and N. cinerea is resistant. Jbtx causes harmful effects and death on several insect species, belonging to the orders Hemiptera ( Oncopeltus fasciatus, Dysdercus peruvianus ), Diptera ( Aedes aegypti ), Lepidoptera ( Spodoptera frugiperda and Helicoverpa armigera ; Becker‐Ritt, Portugal, & Carlini, 2017), and Blattodea ( Blattella germanica ; Carlini & Ligabue‐Braun, 2016). Species‐specific selectivity effects within the Blattodea order were already described for the spider venom tested on B. germanica and Periplaneta americana (Bende et al, 2015; Herzig et al, 2016).…”

Structure-Function Insights of Jaburetox and Soyuretox: Novel Intrinsically Disordered Polypeptides Derived from Plant Ureases

“…The percentage of phospholipids varied individually [106]. Interestingly, both microorganisms are susceptible to Jaburetox [60,61]. [77]; (4) Fruttero et al, [82]; (5) Coste Grahl et al, [83]; (6) Kappaun et al, [64]; (7) and (8) unpublished results; (9) Staniscuaski et al, [81].…”

“…Jaburetox is lethal to several insects susceptible to canatoxin (the cotton stainer bug D. peruvianus , the kissing bugs R. prolixus and Triatoma infestans ) and also kills insects that are resistant to intact ureases, such as lepidopterans (fall armyworm Spodoptora frugiperda , cotton bollworm Helicoverpa armigera ) and dipterans ( Aedes aegypti ) [ 57 , 60 ], because the hydrolysis of the protein to release the peptide is no longer required.…”

“…The antimicrobial activity of Jaburetox against some bacteria such as Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was observed in preliminary assays in the dose range of 0.25 μM to 13.5 μM [ 60 ]. As described earlier, Jaburetox was shown to permeabilize model membranes, as LUVs and PLBs, composed by different phospholipids and net charges; phosphatidylglycerol (PG) and phosphatidic acid (PA) with negative charges and the neutral phosphatidylethanolamine (PE), phosphatidylcholine (PC) and cholesterol (Ch) [ 66 , 76 ].…”

“…The percentage of phospholipids varied individually [ 106 ]. Interestingly, both microorganisms are susceptible to Jaburetox [ 60 , 61 ].…”