Abstract
Ascaris suum and Ascaris lumbricoides are two closely related geo-helminth parasites that ubiquitously infect pigs and humans, respectively. Ascaris suum infection in pigs is considered a good model for A. lumbricoides infection in humans because of a similar biology and tissue migration to the intestines. Ascaris lumbricoides infections in children are associated with malnutrition, growth and cognitive stunting, immune defects, and, in extreme cases, life-threatening blockage of the digestive tract and aberrant migration into the bile duct and peritoneum. Similar effects can be seen with A. suum infections in pigs related to poor feed efficiency and performance. New strategies to control Ascaris infections are needed largely due to reduced treatment efficacies of current anthelmintics in the field, the threat of resistance development, and the general lack of new drug development for intestinal soil-transmitted helminths for humans and animals. Here we demonstrate for the first time that A. suum expresses the receptors for Bacillus thuringiensis crystal protein and novel anthelmintic Cry5B, which has been previously shown to intoxicate hookworms and which belongs to a class of proteins considered non-toxic to vertebrates. Cry5B is able to intoxicate A. suum larvae and adults and triggers the activation of the p38 mitogen-activated protein kinase pathway similar to that observed with other nematodes. Most importantly, two moderate doses of 20 mg/kg body weight (143 nM/kg) of Cry5B resulted in a near complete cure of intestinal A. suum infections in pigs. Taken together, these results demonstrate the excellent potential of Cry5B to treat Ascaris infections in pigs and in humans and for Cry5B to work effectively in the human gastrointestinal tract.
Highlights
Ascaris lumbricoides, the large roundworm, is the most common parasitic nematode infection of humans with estimates of more than one billion people infected worldwide in mostly lesser developed countries [1]
Ascaris suum is an intestinal parasitic nematode of pigs that is very closely related to Ascaris lumbricoides, a major intestinal parasitic nematode of humans that infects more than one billion people worldwide
We test against A. suum infections the effectiveness of Cry5B, a nematode-killing protein made by the natural soil bacterium Bacillus thuringiensis and representing a promising new class of anthelmintics
Summary
The large roundworm, is the most common parasitic nematode infection of humans with estimates of more than one billion people infected worldwide in mostly lesser developed countries [1]. Chronic infections in humans are associated with growth and cognitive stunting, impaired nutritional status, and dysfunctional immune regulation related to a polarized Th2 immunity and altered protective antibody responses to bacterial vaccination [1,2,3,4]. Adverse effects in pigs are similar to those in humans and include migrating larvaeinduced liver scaring (white spots), pulmonary inflammation, reduced nutritional absorption and feed efficiency, altered responses to bacterial vaccination, and a polarized Th2 immunity [4,12,13,14,15]. Ascaris suum and A. lumbricoides are genetically similar and there is currently some evidence that they are the same species [16]
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