A Wolf in Another Wolf’s Clothing: Post-Genomic Regulation Dictates Venom Profiles of Medically-Important Cryptic Kraits in India

The Common Krait (<i>Bungarus caeruleus</i>) shares a distribution range with many other ‘phenotypically-similar’ kraits across the Indian subcontinent. Despite several reports of fatal envenomings by other <i>Bungarus</i> species, commercial Indian antivenoms are only manufa...

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Main Authors: Kartik Sunagar, Suyog Khochare, R. R. Senji Laxme, Saurabh Attarde, Paulomi Dam, Vivek Suranse, Anil Khaire, Gerard Martin, Ashok Captain
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/13/1/69
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author Kartik Sunagar
Suyog Khochare
R. R. Senji Laxme
Saurabh Attarde
Paulomi Dam
Vivek Suranse
Anil Khaire
Gerard Martin
Ashok Captain
author_facet Kartik Sunagar
Suyog Khochare
R. R. Senji Laxme
Saurabh Attarde
Paulomi Dam
Vivek Suranse
Anil Khaire
Gerard Martin
Ashok Captain
author_sort Kartik Sunagar
collection DOAJ
description The Common Krait (<i>Bungarus caeruleus</i>) shares a distribution range with many other ‘phenotypically-similar’ kraits across the Indian subcontinent. Despite several reports of fatal envenomings by other <i>Bungarus</i> species, commercial Indian antivenoms are only manufactured against <i>B. caeruleus</i>. 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 (<i>Bungarus romulusi</i> 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 (<i>B. sindanus walli</i>) as previously believed, but are genetically very similar to <i>B. sindanus</i> 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 <i>B. caeruleus</i> was neutralised as per the manufacturer’s claim, performance against the venoms of <i>B. sindanus</i> and <i>B. romulusi</i> was poor, highlighting the need for regionally-effective antivenoms in India.
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spelling doaj.art-e6021c0945a340d3b717e62be820f81e2023-12-03T13:44:18ZengMDPI AGToxins2072-66512021-01-011316910.3390/toxins13010069A Wolf in Another Wolf’s Clothing: Post-Genomic Regulation Dictates Venom Profiles of Medically-Important Cryptic Kraits in IndiaKartik Sunagar0Suyog Khochare1R. R. Senji Laxme2Saurabh Attarde3Paulomi Dam4Vivek Suranse5Anil Khaire6Gerard Martin7Ashok Captain8Evolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, Karnataka, IndiaEvolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, Karnataka, IndiaEvolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, Karnataka, IndiaEvolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, Karnataka, IndiaEvolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, Karnataka, IndiaEvolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, Karnataka, IndiaIndian Herpetological Society, 7/47, Pune Satara Road, Pune 411009, Maharashtra, IndiaThe Liana Trust, Survey #1418/1419 Rathnapuri, Hunsur 571189, Karnataka, India3/1 Boat Club Road, Pune 411001, Maharashtra, IndiaThe Common Krait (<i>Bungarus caeruleus</i>) shares a distribution range with many other ‘phenotypically-similar’ kraits across the Indian subcontinent. Despite several reports of fatal envenomings by other <i>Bungarus</i> species, commercial Indian antivenoms are only manufactured against <i>B. caeruleus</i>. 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 (<i>Bungarus romulusi</i> 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 (<i>B. sindanus walli</i>) as previously believed, but are genetically very similar to <i>B. sindanus</i> 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 <i>B. caeruleus</i> was neutralised as per the manufacturer’s claim, performance against the venoms of <i>B. sindanus</i> and <i>B. romulusi</i> was poor, highlighting the need for regionally-effective antivenoms in India.https://www.mdpi.com/2072-6651/13/1/69venom evolutionnew krait species from Indiaantivenom therapyvenom proteomicsvenom gland transcriptomicsRomulus’ krait
spellingShingle Kartik Sunagar
Suyog Khochare
R. R. Senji Laxme
Saurabh Attarde
Paulomi Dam
Vivek Suranse
Anil Khaire
Gerard Martin
Ashok Captain
A Wolf in Another Wolf’s Clothing: Post-Genomic Regulation Dictates Venom Profiles of Medically-Important Cryptic Kraits in India
Toxins
venom evolution
new krait species from India
antivenom therapy
venom proteomics
venom gland transcriptomics
Romulus’ krait
title A Wolf in Another Wolf’s Clothing: Post-Genomic Regulation Dictates Venom Profiles of Medically-Important Cryptic Kraits in India
title_full A Wolf in Another Wolf’s Clothing: Post-Genomic Regulation Dictates Venom Profiles of Medically-Important Cryptic Kraits in India
title_fullStr A Wolf in Another Wolf’s Clothing: Post-Genomic Regulation Dictates Venom Profiles of Medically-Important Cryptic Kraits in India
title_full_unstemmed A Wolf in Another Wolf’s Clothing: Post-Genomic Regulation Dictates Venom Profiles of Medically-Important Cryptic Kraits in India
title_short A Wolf in Another Wolf’s Clothing: Post-Genomic Regulation Dictates Venom Profiles of Medically-Important Cryptic Kraits in India
title_sort wolf in another wolf s clothing post genomic regulation dictates venom profiles of medically important cryptic kraits in india
topic venom evolution
new krait species from India
antivenom therapy
venom proteomics
venom gland transcriptomics
Romulus’ krait
url https://www.mdpi.com/2072-6651/13/1/69
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