Pyrethroid Resistance in Malaysian Populations of Dengue Vector Aedes aegypti Is Mediated by CYP9 Family of Cytochrome P450 Genes
Dengue control and prevention rely heavily on insecticide-based interventions. However, insecticide resistance in the dengue vector Aedes aegypti, threatens the continued effectiveness of these tools. The molecular basis of the resistance remains uncharacterised in many endemic countries including M...
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| Veröffentlicht in: | PLoS neglected tropical diseases 2017-01, Vol.11 (1), p.e0005302 |
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| creator | Ishak, Intan H Kamgang, Basile Ibrahim, Sulaiman S Riveron, Jacob M Irving, Helen Wondji, Charles S |
| description | Dengue control and prevention rely heavily on insecticide-based interventions. However, insecticide resistance in the dengue vector Aedes aegypti, threatens the continued effectiveness of these tools. The molecular basis of the resistance remains uncharacterised in many endemic countries including Malaysia, preventing the design of evidence-based resistance management. Here, we investigated the underlying molecular basis of multiple insecticide resistance in Ae. aegypti populations across Malaysia detecting the major genes driving the metabolic resistance.
Genome-wide microarray-based transcription analysis was carried out to detect the genes associated with metabolic resistance in these populations. Comparisons of the susceptible New Orleans strain to three non-exposed multiple insecticide resistant field strains; Penang, Kuala Lumpur and Kota Bharu detected 2605, 1480 and 425 differentially expressed transcripts respectively (fold-change>2 and p-value ≤ 0.05). 204 genes were commonly over-expressed with monooxygenase P450 genes (CYP9J27, CYP6CB1, CYP9J26 and CYP9M4) consistently the most up-regulated detoxification genes in all populations, indicating that they possibly play an important role in the resistance. In addition, glutathione S-transferases, carboxylesterases and other gene families commonly associated with insecticide resistance were also over-expressed. Gene Ontology (GO) enrichment analysis indicated an over-representation of GO terms linked to resistance such as monooxygenases, carboxylesterases, glutathione S-transferases and heme-binding. Polymorphism analysis of CYP9J27 sequences revealed a high level of polymorphism (except in Joho Bharu), suggesting a limited directional selection on this gene. In silico analysis of CYP9J27 activity through modelling and docking simulations suggested that this gene is involved in the multiple resistance in Malaysian populations as it is predicted to metabolise pyrethroids, DDT and bendiocarb.
The predominant over-expression of cytochrome P450s suggests that synergist-based (PBO) control tools could be utilised to improve control of this major dengue vector across Malaysia. |
| doi_str_mv | 10.1371/journal.pntd.0005302 |
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Genome-wide microarray-based transcription analysis was carried out to detect the genes associated with metabolic resistance in these populations. Comparisons of the susceptible New Orleans strain to three non-exposed multiple insecticide resistant field strains; Penang, Kuala Lumpur and Kota Bharu detected 2605, 1480 and 425 differentially expressed transcripts respectively (fold-change>2 and p-value ≤ 0.05). 204 genes were commonly over-expressed with monooxygenase P450 genes (CYP9J27, CYP6CB1, CYP9J26 and CYP9M4) consistently the most up-regulated detoxification genes in all populations, indicating that they possibly play an important role in the resistance. In addition, glutathione S-transferases, carboxylesterases and other gene families commonly associated with insecticide resistance were also over-expressed. Gene Ontology (GO) enrichment analysis indicated an over-representation of GO terms linked to resistance such as monooxygenases, carboxylesterases, glutathione S-transferases and heme-binding. Polymorphism analysis of CYP9J27 sequences revealed a high level of polymorphism (except in Joho Bharu), suggesting a limited directional selection on this gene. In silico analysis of CYP9J27 activity through modelling and docking simulations suggested that this gene is involved in the multiple resistance in Malaysian populations as it is predicted to metabolise pyrethroids, DDT and bendiocarb.
The predominant over-expression of cytochrome P450s suggests that synergist-based (PBO) control tools could be utilised to improve control of this major dengue vector across Malaysia.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0005302</identifier><identifier>PMID: 28114328</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aedes - drug effects ; Aedes - enzymology ; Aedes - genetics ; Animals ; Annotations ; Aquatic insects ; Biology ; Biology and Life Sciences ; Cytochrome ; Cytochrome P-450 Enzyme System - genetics ; Cytochrome P-450 Enzyme System - metabolism ; Dengue - transmission ; Detoxification ; Female ; Funding ; Genes ; Genetic polymorphisms ; Insect Proteins - genetics ; Insect Proteins - metabolism ; Insect Vectors - drug effects ; Insect Vectors - enzymology ; Insect Vectors - genetics ; Insecticide Resistance ; Insecticides ; Insecticides - pharmacology ; Investigations ; Malaysia ; Medicine ; Medicine and Health Sciences ; Metabolism ; Ontology ; Pesticides ; Polymorphism, Genetic ; Pyrethrins - pharmacology ; Pyrethroids ; Research and Analysis Methods ; Tropical diseases ; Vector-borne diseases ; Yellow fever mosquito ; Zika virus</subject><ispartof>PLoS neglected tropical diseases, 2017-01, Vol.11 (1), p.e0005302</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Is Mediated by CYP9 Family of Cytochrome P450 Genes. PLoS Negl Trop Dis 11(1): e0005302. doi:10.1371/journal.pntd.0005302</rights><rights>2017 Ishak et al 2017 Ishak et al</rights><rights>2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Is Mediated by CYP9 Family of Cytochrome P450 Genes. PLoS Negl Trop Dis 11(1): e0005302. doi:10.1371/journal.pntd.0005302</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-8f7f74c6b5735b700be83c364274098c33f7cb5d941bbdbf8a4722e79203c2e23</citedby><cites>FETCH-LOGICAL-c624t-8f7f74c6b5735b700be83c364274098c33f7cb5d941bbdbf8a4722e79203c2e23</cites><orcidid>0000-0003-0791-3673</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289618/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289618/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28114328$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Apperson, Charles</contributor><creatorcontrib>Ishak, Intan H</creatorcontrib><creatorcontrib>Kamgang, Basile</creatorcontrib><creatorcontrib>Ibrahim, Sulaiman S</creatorcontrib><creatorcontrib>Riveron, Jacob M</creatorcontrib><creatorcontrib>Irving, Helen</creatorcontrib><creatorcontrib>Wondji, Charles S</creatorcontrib><title>Pyrethroid Resistance in Malaysian Populations of Dengue Vector Aedes aegypti Is Mediated by CYP9 Family of Cytochrome P450 Genes</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Dengue control and prevention rely heavily on insecticide-based interventions. However, insecticide resistance in the dengue vector Aedes aegypti, threatens the continued effectiveness of these tools. The molecular basis of the resistance remains uncharacterised in many endemic countries including Malaysia, preventing the design of evidence-based resistance management. Here, we investigated the underlying molecular basis of multiple insecticide resistance in Ae. aegypti populations across Malaysia detecting the major genes driving the metabolic resistance.
Genome-wide microarray-based transcription analysis was carried out to detect the genes associated with metabolic resistance in these populations. Comparisons of the susceptible New Orleans strain to three non-exposed multiple insecticide resistant field strains; Penang, Kuala Lumpur and Kota Bharu detected 2605, 1480 and 425 differentially expressed transcripts respectively (fold-change>2 and p-value ≤ 0.05). 204 genes were commonly over-expressed with monooxygenase P450 genes (CYP9J27, CYP6CB1, CYP9J26 and CYP9M4) consistently the most up-regulated detoxification genes in all populations, indicating that they possibly play an important role in the resistance. In addition, glutathione S-transferases, carboxylesterases and other gene families commonly associated with insecticide resistance were also over-expressed. Gene Ontology (GO) enrichment analysis indicated an over-representation of GO terms linked to resistance such as monooxygenases, carboxylesterases, glutathione S-transferases and heme-binding. Polymorphism analysis of CYP9J27 sequences revealed a high level of polymorphism (except in Joho Bharu), suggesting a limited directional selection on this gene. In silico analysis of CYP9J27 activity through modelling and docking simulations suggested that this gene is involved in the multiple resistance in Malaysian populations as it is predicted to metabolise pyrethroids, DDT and bendiocarb.
The predominant over-expression of cytochrome P450s suggests that synergist-based (PBO) control tools could be utilised to improve control of this major dengue vector across Malaysia.</description><subject>Aedes - drug effects</subject><subject>Aedes - enzymology</subject><subject>Aedes - genetics</subject><subject>Animals</subject><subject>Annotations</subject><subject>Aquatic insects</subject><subject>Biology</subject><subject>Biology and Life Sciences</subject><subject>Cytochrome</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Dengue - transmission</subject><subject>Detoxification</subject><subject>Female</subject><subject>Funding</subject><subject>Genes</subject><subject>Genetic polymorphisms</subject><subject>Insect Proteins - genetics</subject><subject>Insect Proteins - metabolism</subject><subject>Insect Vectors - drug effects</subject><subject>Insect Vectors - enzymology</subject><subject>Insect Vectors - 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drug effects</topic><topic>Aedes - enzymology</topic><topic>Aedes - genetics</topic><topic>Animals</topic><topic>Annotations</topic><topic>Aquatic insects</topic><topic>Biology</topic><topic>Biology and Life Sciences</topic><topic>Cytochrome</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Dengue - transmission</topic><topic>Detoxification</topic><topic>Female</topic><topic>Funding</topic><topic>Genes</topic><topic>Genetic polymorphisms</topic><topic>Insect Proteins - genetics</topic><topic>Insect Proteins - metabolism</topic><topic>Insect Vectors - drug effects</topic><topic>Insect Vectors - enzymology</topic><topic>Insect Vectors - genetics</topic><topic>Insecticide Resistance</topic><topic>Insecticides</topic><topic>Insecticides - pharmacology</topic><topic>Investigations</topic><topic>Malaysia</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Ontology</topic><topic>Pesticides</topic><topic>Polymorphism, Genetic</topic><topic>Pyrethrins - 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However, insecticide resistance in the dengue vector Aedes aegypti, threatens the continued effectiveness of these tools. The molecular basis of the resistance remains uncharacterised in many endemic countries including Malaysia, preventing the design of evidence-based resistance management. Here, we investigated the underlying molecular basis of multiple insecticide resistance in Ae. aegypti populations across Malaysia detecting the major genes driving the metabolic resistance.
Genome-wide microarray-based transcription analysis was carried out to detect the genes associated with metabolic resistance in these populations. Comparisons of the susceptible New Orleans strain to three non-exposed multiple insecticide resistant field strains; Penang, Kuala Lumpur and Kota Bharu detected 2605, 1480 and 425 differentially expressed transcripts respectively (fold-change>2 and p-value ≤ 0.05). 204 genes were commonly over-expressed with monooxygenase P450 genes (CYP9J27, CYP6CB1, CYP9J26 and CYP9M4) consistently the most up-regulated detoxification genes in all populations, indicating that they possibly play an important role in the resistance. In addition, glutathione S-transferases, carboxylesterases and other gene families commonly associated with insecticide resistance were also over-expressed. Gene Ontology (GO) enrichment analysis indicated an over-representation of GO terms linked to resistance such as monooxygenases, carboxylesterases, glutathione S-transferases and heme-binding. Polymorphism analysis of CYP9J27 sequences revealed a high level of polymorphism (except in Joho Bharu), suggesting a limited directional selection on this gene. In silico analysis of CYP9J27 activity through modelling and docking simulations suggested that this gene is involved in the multiple resistance in Malaysian populations as it is predicted to metabolise pyrethroids, DDT and bendiocarb.
The predominant over-expression of cytochrome P450s suggests that synergist-based (PBO) control tools could be utilised to improve control of this major dengue vector across Malaysia.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28114328</pmid><doi>10.1371/journal.pntd.0005302</doi><orcidid>https://orcid.org/0000-0003-0791-3673</orcidid><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central Open Access; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Aedes - drug effects Aedes - enzymology Aedes - genetics Animals Annotations Aquatic insects Biology Biology and Life Sciences Cytochrome Cytochrome P-450 Enzyme System - genetics Cytochrome P-450 Enzyme System - metabolism Dengue - transmission Detoxification Female Funding Genes Genetic polymorphisms Insect Proteins - genetics Insect Proteins - metabolism Insect Vectors - drug effects Insect Vectors - enzymology Insect Vectors - genetics Insecticide Resistance Insecticides Insecticides - pharmacology Investigations Malaysia Medicine Medicine and Health Sciences Metabolism Ontology Pesticides Polymorphism, Genetic Pyrethrins - pharmacology Pyrethroids Research and Analysis Methods Tropical diseases Vector-borne diseases Yellow fever mosquito Zika virus |
| title | Pyrethroid Resistance in Malaysian Populations of Dengue Vector Aedes aegypti Is Mediated by CYP9 Family of Cytochrome P450 Genes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T09%3A37%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pyrethroid%20Resistance%20in%20Malaysian%20Populations%20of%20Dengue%20Vector%20Aedes%20aegypti%20Is%20Mediated%20by%20CYP9%20Family%20of%20Cytochrome%20P450%20Genes&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=Ishak,%20Intan%20H&rft.date=2017-01-23&rft.volume=11&rft.issue=1&rft.spage=e0005302&rft.pages=e0005302-&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0005302&rft_dat=%3Cgale_plos_%3EA493816556%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1869528915&rft_id=info:pmid/28114328&rft_galeid=A493816556&rft_doaj_id=oai_doaj_org_article_6d42b611a781469b93607815996eada4&rfr_iscdi=true |