Abstract
BackgroundThe king cobra (Ophiophagus hannah) is widely distributed throughout many parts of Asia. This study aims to investigate the complexity of Malaysian Ophiophagus hannah (MOh) venom for a better understanding of king cobra venom variation and its envenoming pathophysiology. The venom gland transcriptome was investigated using the Illumina HiSeq™ platform, while the venom proteome was profiled by 1D-SDS-PAGE-nano-ESI-LCMS/MS.ResultsTranscriptomic results reveal high redundancy of toxin transcripts (3357.36 FPKM/transcript) despite small cluster numbers, implying gene duplication and diversification within restricted protein families. Among the 23 toxin families identified, three-finger toxins (3FTxs) and snake-venom metalloproteases (SVMPs) have the most diverse isoforms. These 2 toxin families are also the most abundantly transcribed, followed in descending order by phospholipases A2 (PLA2s), cysteine-rich secretory proteins (CRISPs), Kunitz-type inhibitors (KUNs), and L-amino acid oxidases (LAAOs). Seventeen toxin families exhibited low mRNA expression, including hyaluronidase, DPP-IV and 5’-nucleotidase that were not previously reported in the venom-gland transcriptome of a Balinese O. hannah. On the other hand, the MOh proteome includes 3FTxs, the most abundantly expressed proteins in the venom (43 % toxin sbundance). Within this toxin family, there are 6 long-chain, 5 short-chain and 2 non-conventional 3FTx. Neurotoxins comprise the major 3FTxs in the MOh venom, consistent with rapid neuromuscular paralysis reported in systemic envenoming. The presence of toxic enzymes such as LAAOs, SVMPs and PLA2 would explain tissue inflammation and necrotising destruction in local envenoming. Dissimilarities in the subtypes and sequences between the neurotoxins of MOh and Naja kaouthia (monocled cobra) are in agreement with the poor cross-neutralization activity of N. kaouthia antivenom used against MOh venom. Besides, the presence of cobra venom factor, nerve growth factors, phosphodiesterase, 5’-nucleotidase, and DPP-IV in the venom proteome suggests its probable hypotensive action in subduing prey.ConclusionThis study reports the diversity and abundance of toxins in the venom of the Malaysian king cobra (MOh). The results correlate with the pathophysiological actions of MOh venom, and dispute the use of Naja cobra antivenoms to treat MOh envenomation. The findings also provide a deeper insight into venom variations due to geography, which is crucial for the development of a useful pan-regional antivenom.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1828-2) contains supplementary material, which is available to authorized users.
Highlights
The king cobra (Ophiophagus hannah) is widely distributed throughout many parts of Asia
From the Snake venom metalloproteinase (SVMP) transcript sequences of Malaysian Ophiophagus hannah (MOh), we identified the absence of the seventh cysteine residue in Domain M that takes part in the disulfide bond exchange for autolysis during secretion or formation of the biologically active DC domain, typical for Viperidae SVMP-PIIIs [52, 53]
Remarkable variations are noted within the Group I Phospholipase A2 (PLA2) among king cobra venoms of different origin: while we identified Group IA PLA2 from MOh, Huang et al [63] isolated only Group IB PLA2 from a Fujian Chinese sample; Vonk et al [20] identified two each for Group IA and Group IB from a Balinese sample; Vejayan et al [24] identified one each of Group IA and Group IB from a Malaysian sample; Danpaiboon et al [25] identified 2 Group IA and 1 Group IB PLA2 from a Thai sample
Summary
The king cobra (Ophiophagus hannah) is widely distributed throughout many parts of Asia. This study aims to investigate the complexity of Malaysian Ophiophagus hannah (MOh) venom for a better understanding of king cobra venom variation and its envenoming pathophysiology. Tan et al BMC Genomics (2015) 16:687 multiple isoforms within each major toxin family, resulting in diverse functional variations of venom proteins that have great impacts on medical management and toxinological research [4]. The phenomenon complicates snakebite management that relies heavily on the understanding of venom complexity and the availability of effective antivenom. Among the native snakes in Malaysia, the king cobra (Ophiophagus hannah) is a known cause of envenomation [6, 7], partly due to its popularity among snake hobbyists. King cobra bites cause neurotoxicty, paralysing respiratory muscles and leading to rapid death if untreated. The bites can result in extensive tissue necrosis and crippling deformity, adding to the heavy toll of human suffering in socioeconomically deprived countries
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