Abstract
The Common Krait (Bungarus caeruleus) shares a distribution range with many other ‘phenotypically-similar’ kraits across the Indian subcontinent. Despite several reports of fatal envenomings by other Bungarus species, commercial Indian antivenoms are only manufactured against B. caeruleus. It is, therefore, imperative to understand the distribution of genetically distinct lineages of kraits, the compositional differences in their venoms, and the consequent impact of venom variation on the (pre)clinical effectiveness of antivenom therapy. To address this knowledge gap, we conducted phylogenetic and comparative venomics investigations of kraits in Southern and Western India. Phylogenetic reconstructions using mitochondrial markers revealed a new species of krait, Romulus’ krait (Bungarus romulusi sp. nov.), in Southern India. Additionally, we found that kraits with 17 mid-body dorsal scale rows in Western India do not represent a subspecies of the Sind Krait (B. sindanus walli) as previously believed, but are genetically very similar to B. sindanus in Pakistan. Furthermore, venom proteomics and comparative transcriptomics revealed completely contrasting venom profiles. While the venom gland transcriptomes of all three species were highly similar, venom proteomes and toxicity profiles differed significantly, suggesting the prominent role of post-genomic regulatory mechanisms in shaping the venoms of these cryptic kraits. In vitro venom recognition and in vivo neutralisation experiments revealed a strong negative impact of venom variability on the preclinical performance of commercial antivenoms. While the venom of B. caeruleus was neutralised as per the manufacturer’s claim, performance against the venoms of B. sindanus and B. romulusi was poor, highlighting the need for regionally-effective antivenoms in India.
Highlights
By reconstructing species’ phylogenetic histories using mitochondrial markers (NADH-ubiquinone oxidoreductase chain 4 (ND4) and cytochrome b), we show that kraits with 17 dorsal scale rows (DSR) in Western India do not represent the subspecies B. sindanus walli as previously believed, but are genetically indistinguishable from the Sind krait (B. sindanus) in Pakistan
Through the use of comparative venom proteomics and venom gland transcriptomics, we show that the significant compositional differences in the venoms of cryptic kraits in Southern and Western India likely result from post-genomic regulatory mechanisms
Sequences from the 17-mid-body scale row krait from Maharashtra were found in the same clade as B. sindanus from Pakistan (BPP: 1; BS: 100)
Summary
The Common Krait (Bungarus caeruleus), one of the ‘big four’ medically most-important. Indian snakes, is well-known for causing numerous fatal envenomings in the country [1,2]. Considering the near countrywide distribution of this clinically important snake, B. caeruleus venoms are used for the manufacture of commercial Indian polyvalent antivenoms. Several reports of fatal envenomings by other superficially similar Bungarus species, which share a distribution range with B. caeruleus, have come to light [4,5]. Their venoms are not used for the manufacture of the life-saving antivenom, and the ‘big four’ antivenom is routinely used for the treatment of envenomings from such neglected species
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