First report of AChE1 (G119S) mutation and multiple resistance mechanisms in Anopheles gambiae s.s. in nigeria ifeoluwa Kayode fagbohun 1 ✉ , emmanuel taiwo idowu 1 , olubunmi Adetoro otubanjo 1 & taiwo Samson Awolola 2 Susceptibility and PBO synergist bioassays were done using 3-5 days old female Anopheles mosquito collected from Lagos State, Nigeria with WHO test papers DDT (4%), permethrin (0.75%), Bendiocarb (1%) and PBO (4%) according to standard procedures. The activities of cytochrome P450s, glutathione S-transferase and carboxylesterases were determined using biochemical assays. the presence of kdr-w, kdr-e and Ace-1 R mutations were examined using molecular assays. Resistance to DDt and permethrin in An gambiae s.s from the four Local Government Areas (LGAs) was recorded while suspected resistance to bendiocarb was recorded in mosquitoes from Alimosho and Kosofe LGAs. PBO synergist reduced the knockdown time and also recorded significantly (P < 0.05) higher 24 hrs percentage mortality compared to non-synergized bioassays. Increased activities of detoxifying enzymes was recorded in wild mosquito compared to the insecticides susceptible laboratory strain and this was significant (P < 0.05) in P450s, esterase α and β. Kdr-w was detected in An. gambiae s.s from all the LGAs, kdr-e (L1014S) was detected in Alimosho, Kosofe and ibeju-Lekki, while the Ace-1 R gene was detected in Alimosho and Kosofe. Results from this study provide evidence for resistance of An. gambiae from Lagos State to multiple classes of neurotoxic insecticides with multiple resistance mechanisms to these insecticides.