The XylC-mediated aromatic metabolic network modulates the metabolic response of Pseudomonas aeruginosa to deltamethrin.

The widespread emergence of pyrethroid resistance represents a major challenge in pest and vector management. This study examined the function of the xylC-encoded benzaldehyde dehydrogenase in Pseudomonas aeruginosa under deltamethrin stress. The metabolic response of a ΔxylC mutant cultured with 50 mg/L deltamethrin was compared to the wild-type strain, and functional complementation was achieved by adding purified XylC protein. Integrated metabolomic and proteomic analyses were used to characterize the associated metabolic adaptations. Deltamethrin exposure inhibited the production of 3-(2-carboxyvinyl)-naphthalene-2-carboxylic acid whilst upregulated cbb3-type cytochrome c oxidase. The progressively increasing abundance of cbb3 oxidase from the NM to psd to knp groups revealed fundamental hypoxic response that maintain bioenergetic homeostasis during compound metabolic challenges. Following exposure to deltamethrin, P. aeruginosa exhibited accumulation of aromatic intermediates, including benzyl alcohol, benzoate esters, benzamide, 4-hydroxybenzoate, and 1,3-benzenediol, indicating a coordinated metabolic response to this synthetic pyrethroid. The xylC knockout disrupted aromatic compound degradation but activated alternative pathways, highlighting the organism's metabolic plasticity. Core metabolism routes were elucidated, revealing the transformation of toluene to benzoate via benzyl alcohol and benzaldehyde; the conversion of xylene to β-ketoadipate through methylbenzoate and 3-methylcatechol; and the pathway from benzoate to reductive ring cleavage involving benzoyl-CoA. As an insecticide with a diphenyl structure, deltamethrin induces broad changes in the aromatic hydrocarbon metabolism of P. aeruginosa. These metabolic alterations may help the bacterium adapt to deltamethrin stress and support the maintenance of redox balance under the resulting oxidative conditions.