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by double-stranded RNA. Nature 2004,431(7006):343–349.PubMedCrossRef Competing interests The authors declare that they have no competing interests. Authors’ contributions Experiments were conceived by SM and KAH and performed by SM. Data was analyzed by SM and KAH. The manuscript was written by SM and KAH. All authors have read and #GDC-0449 nmr randurls[1|1|,|CHEM1|]# approved the final manuscript.”
“Background The gut epithelium and its associated selleck chemicals llc microorganisms provide an important barrier that protects animals from the external environment. This barrier serves both to prevent invasion by potential pathogens and limit the elicitation of host responses to the resident microbiota [1, 2]. Dysfunction of this barrier, which can occur as a result of alterations of the normal gut ecology, impairment of host immune defenses, or physical disruption of intestinal epithelia, may lead to pathological states [3–6]. To breach the gut barrier, many
enteric pathogens have evolved specific strategies such as production of toxins that physically disrupt cells of the gut epithelium [7–11]. B. thuringiensis kills insects through the production of
such toxins, designated insecticidal crystal proteins. Following ingestion of B. thuringiensis by susceptible larvae, these toxins initiate killing of insects through a multi-step process that includes the formation of pores and lysis of midgut epithelial cells [12–15]. Despite a detailed understanding of the mechanisms of toxin binding and disruption of the midgut epithelium, we know less about the subsequent events that cause larval mortality. Three mechanisms, which account for differences among host responses, have been suggested as the ultimate cause of larval death. The first, in which larvae die from toxin ingestion within hours or a day, is attributed to direct toxemia [13, 16, 17]. The second, DOK2 in which prolonged feeding on B. thuringiensis leads to developmental arrest and eventual death is thought to occur by starvation [18–20]. The third, and most commonly cited mechanism is sepsis due to the growth of B. thuringiensis in the hemocoel following translocation of spores from the toxin-damaged gut into the hemolymph [12, 13, 21, 22]. However, despite numerous reports of growth of B. thuringiensis in dead or moribund larvae [23–26], there is little evidence of B. thuringiensis proliferation in insect hemolymph prior to death. In addition, the proposed mechanism of death by B.