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Muhammad, Abdullahi (2022) Environmental pollution drives metabolic insecticide resistance in the major malaria vector Anopheles coluzzii in Nigeria, Thesis (Doctoral), Liverpool School of Tropical Medicine.
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A Muhammad - Thesis FINAL.pdf - Accepted Version Restricted to Repository staff only until 1 January 2025. Download (5MB) |
Abstract
Vector control tools rely heavily on the use of chemical insecticides in the forms of IRS and LLINs. Resistance has been reported to most of these insecticides in different parts of the globe. The resistance is said to evolve due to the intensive use of the insecticides in public health and agriculture thereby increasing the selection pressure. Environmental pollutants are also posing as additional selection pressures. The impact of agriculture on the evolution of resistance has been extensively studied while the environmental pollution has received little attention recently. Polycyclic aromatic hydrocarbons derived from the incomplete combustion of organic matter is one of the most recalcitrant environmental pollutants generated from oil and gas related activities. Oil pollution is a common problem in many countries with Nigeria having a larger share due to spillage, gas flaring, illegal refineries, operational accidents and pipeline vandals. The PAHs generally serve as ligands to the aryl hydrocarbon receptors involved in the regulation of xenobiotic metabolizing enzymes. Therefore, exposure of mosquito larvae to these pollutants could potentially lead to the overexpression of enzymes involved in insecticides resistance, thus leading to an evolution of cross-resistance if the selected genes are involved in resistance.
To understand the insecticide resistance profile and mechanism of Anopheles coluzzii population surviving in such polluted breeding sites, field population from Port Harcourt Nigeria was collected and characterized. The population was resistant to pyrethroids and DDT but susceptible to organophosphates and carbamates. The resistant mechanisms were a combination of target site and metabolic-based resistance through the overexpression of several candidate genes. Looking at the possible signatures of pollution in a genome-wide transcriptional analysis, two populations of An. coluzzii from polluted breeding sites and one from agricultural sites were compared using the laboratory susceptible strain as baseline control. The populations from polluted site tend to share a lot of transcriptional similarities, e.g. the massive overexpression of CYP9K1 and GSTe2, with signatures of recent selection activities. Many differences may also be attributed to the geography, for example the variations in immune response genes profiles. In addition, several other P450s and GSTs overexpressed in all the populations, CYP6AG2, CYP15B1, CYP6P2 and GSTD3 were overexpressed only in the polluted sites of both northern and southern regions of Nigeria.
Artificial section experiments using select PAH (naphthalene and fluorene) on the field resistant and laboratory susceptible strains of An. coluzzii showed generally an increase in susceptibility for both selected and non-selected lines but with significant differences in the case of DDT and deltamethrin, but not permethrin. Whole genome transcriptional analysis on all the lines revealed the overexpression of several key candidate genes earlier implicated in insecticide resistance. These include several P450s, GSTs, esterases, proteases, SAPs, and cuticular proteins. The most overexpressed of which include the CYP6M4, CYP4C27, and GSTE3. Higher expressions were also seen in genes overlapping known insecticide resistance loci.
Studies using pyrethroid associated recombinant P450s and mosquito microsomes also revealed the possibility of cross-resistance between the PAHs and pyrethroids. Significant metabolism of PAHs by pyrethroids associated P450s and microsomes of pyrethroid resistant strains
In conclusion, PAHs may drive resistance to pyrethroids in populations that survive in polluted breeding waters
| Item Type: | Thesis (Doctoral) | ||||||||||||||
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| Subjects: | QX Parasitology > Insects. Other Parasites > QX 515 Anopheles WA Public Health > Air pollution > WA 754 Pollution and pollutants (incl. tobacco pollution; passive smoking) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Disorders and Injuries of Environmental Origin > WD 600 General works |
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| Faculty: Department: | Biological Sciences > Vector Biology Department | ||||||||||||||
| Depositing User: | Lynn Roberts-Maloney | ||||||||||||||
| Date Deposited: | 10 Nov 2022 10:49 | ||||||||||||||
| Last Modified: | 28 Nov 2023 11:09 | ||||||||||||||
| URI: | https://archive.lstmed.ac.uk/id/eprint/21468 |
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