Investigating the potential role of metabolic resistance genes in conferring cross-resistance to pyrethroids and polycyclic aromatic hydrocarbon pollutants in the major malaria vector Anopheles coluzzii.
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| Title: | Investigating the potential role of metabolic resistance genes in conferring cross-resistance to pyrethroids and polycyclic aromatic hydrocarbon pollutants in the major malaria vector Anopheles coluzzii. |
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| Authors: | Muhammad A; Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool , L3 5QA, United Kingdom. abdullahi.muhammad@lstmed.ac.uk.; Centre for Biotechnology Research Bayero University, Kano, PMB 3011, Nigeria. abdullahi.muhammad@lstmed.ac.uk.; LSTM Research Unit, Centre for Research in Infectious Diseases (CRID), Yaoundé, Cameroon. abdullahi.muhammad@lstmed.ac.uk., Ibrahim SS; Department of Biochemistry, Bayero University, Kano, PMB 3011, Nigeria.; LSTM Research Unit, Centre for Research in Infectious Diseases (CRID), Yaoundé, Cameroon., Ismail HM; Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool , L3 5QA, United Kingdom., Irving H; Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool , L3 5QA, United Kingdom., Paine MJI; Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool , L3 5QA, United Kingdom., Wondji CS; Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool , L3 5QA, United Kingdom.; LSTM Research Unit, Centre for Research in Infectious Diseases (CRID), Yaoundé, Cameroon. |
| Source: | BMC genomics [BMC Genomics] 2025 Nov 07; Vol. 26 (1), pp. 1018. Date of Electronic Publication: 2025 Nov 07. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: BioMed Central Country of Publication: England NLM ID: 100965258 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2164 (Electronic) Linking ISSN: 14712164 NLM ISO Abbreviation: BMC Genomics Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : BioMed Central, [2000- |
| MeSH Terms: | Anopheles*/genetics , Anopheles*/drug effects , Anopheles*/metabolism , Pyrethrins*/pharmacology , Polycyclic Aromatic Hydrocarbons*/pharmacology , Polycyclic Aromatic Hydrocarbons*/metabolism , Insecticide Resistance*/genetics , Mosquito Vectors*/genetics , Mosquito Vectors*/drug effects, Animals ; Cytochrome P-450 Enzyme System/metabolism ; Cytochrome P-450 Enzyme System/genetics ; Insecticides/pharmacology ; Malaria/transmission ; Microsomes/metabolism ; Microsomes/drug effects ; Environmental Pollutants ; Fluorenes/metabolism |
| Abstract: | Competing Interests: Declarations. Ethics approval and consent to participate: Not Applicable. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests. Background: Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous and recalcitrant environmental pollutants generated from petroleum activities and/or biological conversion of organic materials. Environmental exposure of mosquitoes to these pollutants can potentially select resistance to insecticides used in public health for vector control. To understand the cross-resistance potentials between PAHs and pyrethroid insecticides, microsomal fractions prepared from Anopheles coluzzii mosquitoes obtained from agricultural sites and a laboratory susceptible strain, Ngousso, were tested with three major PAHs - fluorene, fluoranthene and naphthalene. Recombinant P450s previously associated with pyrethroid resistance in Anopheles gambiae (CYPs 6M2, 6Z2, 6Z3, 9J5, 6P3, 6P4, 6P5, CYP9K1) and Anopheles funestus CYP6P9a were also used to investigate metabolism of the above PAHs alongside the microsome. Results: Microsomes prepared from pyrethroid-resistant Anopheles coluzzii significantly (P = 0.001, r = 0.99) depleted fluorene and fluoranthene with percentage depletions of 73%±0.5 and 43%0.0 ± 2.2, respectively. A Steady-state kinetic study demonstrated that the microsome has a high affinity for fluorene with a Km and turnover of 58.69 µM ± 20.47 and 37.016 min- 1 ± 3.67, respectively. On the other hand, significant metabolism of fluorene up to 47.9%±2.3 (P = 0.001, r = 0.99) and 52.8%±0.8 (P = 0.001, r = 0.97) depletions were observed with recombinant CYP6P3 and CYP6Z3, respectively. Other P450s showed little to no metabolism with fluorene. CYP6Z2 and CYP6Z3 metabolised fluoranthene with percentage depletions of 50.4%±4.9 (P = 0.003, r = 0.96) and 60.3% ±5.3 (P = 0.002, r = 0.84), respectively. However, no metabolism of naphthalene was observed with all the recombinant P450s used in this study. Conclusion: This study demonstrates that P450 monooxygenases from the malaria vectors can metabolise PAHs, highlighting the potential of these environmental pollutants selecting the P450s, driving insecticide resistance in field populations of major malaria vectors. (© 2025. The Author(s).) |
| References: | Heredity (Edinb). 2012 Dec;109(6):383-92. (PMID: 22948188) J Vector Borne Dis. 2007 Dec;44(4):241-4. (PMID: 18092529) Mol Biol Evol. 2017 May 1;34(5):1261-1275. (PMID: 28204524) Annu Rev Entomol. 2015 Jan 7;60:537-59. (PMID: 25564745) Philos Trans R Soc Lond B Biol Sci. 2013 Jan 06;368(1612):20120429. (PMID: 23297352) PLoS Genet. 2014 Mar 20;10(3):e1004236. (PMID: 24651294) Malar J. 2017 Feb 21;16(1):86. (PMID: 28222727) Curr Drug Metab. 2007 Dec;8(8):822-9. (PMID: 18220563) Infect Dis Poverty. 2019 Dec 3;8(1):100. (PMID: 31796068) Front Psychol. 2013 Nov 26;4:863. (PMID: 24324449) PLoS One. 2012;7(6):e39453. (PMID: 22745756) Curr Protoc Pharmacol. 2016 Sep 16;74:7.8.1-7.8.24. (PMID: 27636111) Drug Metab Lett. 2007 Jan;1(1):67-72. (PMID: 19356021) Xenobiotica. 2018 Jun;48(6):565-575. (PMID: 28648140) Insect Biochem Mol Biol. 2011 Jul;41(7):492-502. (PMID: 21324359) Arch Biochem Biophys. 1997 Sep 15;345(2):342-54. (PMID: 9308909) PLoS Negl Trop Dis. 2014 Jun 19;8(6):e2948. (PMID: 24945250) PLoS One. 2010 Jul 29;5(7):e11872. (PMID: 20686697) Malar J. 2007 Dec 03;6:159. (PMID: 18053173) Acta Trop. 2018 Dec;188:152-160. (PMID: 30179608) Nat Rev Microbiol. 2005 Jan;3(1):81-90. (PMID: 15608702) Int Rev Cytol. 2007;260:35-112. (PMID: 17482904) Anal Biochem. 1976 May 7;72:248-54. (PMID: 942051) Trends Parasitol. 2016 Mar;32(3):187-196. (PMID: 26826784) Genes (Basel). 2018 Mar 02;9(3):. (PMID: 29498712) BMC Infect Dis. 2014 Aug 15;14:441. (PMID: 25127882) Sci Rep. 2020 Oct 1;10(1):16232. (PMID: 33004954) PLoS Genet. 2015 Oct 30;11(10):e1005618. (PMID: 26517127) Parasit Vectors. 2021 Feb 18;14(1):115. (PMID: 33602297) Curr Opin Insect Sci. 2025 Aug;70:101384. (PMID: 40348056) J Biol Chem. 1964 Jul;239:2370-8. (PMID: 14209971) Sci Rep. 2017 Apr 18;7:46451. (PMID: 28417969) Curr Res Parasitol Vector Borne Dis. 2021 Jul 19;1:100041. (PMID: 35284893) Nat Commun. 2023 Aug 16;14(1):4946. (PMID: 37587104) Nat Protoc. 2009;4(9):1245-51. (PMID: 19661994) Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):252-7. (PMID: 23248325) PLoS Genet. 2023 Mar 27;19(3):e1010678. (PMID: 36972302) J Econ Entomol. 1989 Dec;82(6):1559-63. (PMID: 2607028) Insect Mol Biol. 2008 Apr;17(2):125-35. (PMID: 18353102) PLoS Pathog. 2010 Sep 16;6(9):e1001112. (PMID: 20862317) Gene. 2003 Oct 30;318:91-102. (PMID: 14585502) PLoS Genet. 2008 Nov;4(11):e1000286. (PMID: 19043575) Evol Appl. 2015 Apr;8(4):326-45. (PMID: 25926878) Malar J. 2014 Jan 25;13:28. (PMID: 24460952) Biochem J. 2013 Oct 1;455(1):75-85. (PMID: 23844938) Insect Biochem Mol Biol. 2016 Nov;78:50-57. (PMID: 27613592) Trop Med Infect Dis. 2020 Mar 01;5(1):. (PMID: 32121510) PLoS Biol. 2021 Jan 26;19(1):e3000796. (PMID: 33497373) Malar J. 2015 Nov 14;14:453. (PMID: 26573620) Eur J Biochem. 1978 Jul 17;88(1):37-47. (PMID: 27363) Comb Chem High Throughput Screen. 2008 Jul;11(6):469-76. (PMID: 18673274) Arch Insect Biochem Physiol. 1998;37(3):215-24. (PMID: 9465388) PLoS One. 2011;6(12):e28347. (PMID: 22162764) Malar J. 2018 May 18;17(1):204. (PMID: 29776357) Ecotoxicology. 2012 Mar;21(2):465-74. (PMID: 22037695) Insect Biochem Mol Biol. 2013 Apr;43(4):407-16. (PMID: 23123179) Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):25764-25772. (PMID: 31801878) Biomolecules. 2022 Jan 18;12(2):. (PMID: 35204652) Proc Natl Acad Sci U S A. 2018 May 1;115(18):4619-4624. (PMID: 29674455) Mol Ecol. 2022 Jul;31(13):3642-3657. (PMID: 35546741) BMC Genomics. 2014 Sep 27;15:817. (PMID: 25261072) Malar J. 2008 Aug 25;7:163. (PMID: 18724871) Aquat Toxicol. 2012 Jun 15;114-115:49-57. (PMID: 22406618) Arch Insect Biochem Physiol. 2002 Feb;49(2):71-9. (PMID: 11816022) Int J Mol Sci. 2024 Jul 25;25(15):. (PMID: 39125661) Pestic Biochem Physiol. 2019 Nov;161:61-67. (PMID: 31685198) Cell Rep. 2024 Aug 27;43(8):114566. (PMID: 39088320) |
| Grant Information: | (PTDF/17/PHD/ED/1113 Petroleum Technology Development Fund |
| Contributed Indexing: | Keywords: Anopheles coluzzii; Cross-resistance; Cytochrome P450; Insecticide; Malaria; Microsome; Polycyclic aromatic hydrocarbons |
| Substance Nomenclature: | 0 (Pyrethrins) 0 (Polycyclic Aromatic Hydrocarbons) 9035-51-2 (Cytochrome P-450 Enzyme System) 0 (Insecticides) 360UOL779Z (fluoranthene) 0 (Environmental Pollutants) 0 (Fluorenes) |
| Entry Date(s): | Date Created: 20251108 Date Completed: 20251108 Latest Revision: 20251110 |
| Update Code: | 20251110 |
| PubMed Central ID: | PMC12595617 |
| DOI: | 10.1186/s12864-025-12229-x |
| PMID: | 41204404 |
| Database: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstract: | Competing Interests: Declarations. Ethics approval and consent to participate: Not Applicable. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests.<br />Background: Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous and recalcitrant environmental pollutants generated from petroleum activities and/or biological conversion of organic materials. Environmental exposure of mosquitoes to these pollutants can potentially select resistance to insecticides used in public health for vector control. To understand the cross-resistance potentials between PAHs and pyrethroid insecticides, microsomal fractions prepared from Anopheles coluzzii mosquitoes obtained from agricultural sites and a laboratory susceptible strain, Ngousso, were tested with three major PAHs - fluorene, fluoranthene and naphthalene. Recombinant P450s previously associated with pyrethroid resistance in Anopheles gambiae (CYPs 6M2, 6Z2, 6Z3, 9J5, 6P3, 6P4, 6P5, CYP9K1) and Anopheles funestus CYP6P9a were also used to investigate metabolism of the above PAHs alongside the microsome.<br />Results: Microsomes prepared from pyrethroid-resistant Anopheles coluzzii significantly (P = 0.001, r = 0.99) depleted fluorene and fluoranthene with percentage depletions of 73%±0.5 and 43%0.0 ± 2.2, respectively. A Steady-state kinetic study demonstrated that the microsome has a high affinity for fluorene with a Km and turnover of 58.69 µM ± 20.47 and 37.016 min- <sup>1</sup> ± 3.67, respectively. On the other hand, significant metabolism of fluorene up to 47.9%±2.3 (P = 0.001, r = 0.99) and 52.8%±0.8 (P = 0.001, r = 0.97) depletions were observed with recombinant CYP6P3 and CYP6Z3, respectively. Other P450s showed little to no metabolism with fluorene. CYP6Z2 and CYP6Z3 metabolised fluoranthene with percentage depletions of 50.4%±4.9 (P = 0.003, r = 0.96) and 60.3% ±5.3 (P = 0.002, r = 0.84), respectively. However, no metabolism of naphthalene was observed with all the recombinant P450s used in this study.<br />Conclusion: This study demonstrates that P450 monooxygenases from the malaria vectors can metabolise PAHs, highlighting the potential of these environmental pollutants selecting the P450s, driving insecticide resistance in field populations of major malaria vectors.<br /> (© 2025. The Author(s).) |
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| ISSN: | 1471-2164 |
| DOI: | 10.1186/s12864-025-12229-x |