| Summary: | Knowledge about resistance mechanisms can provide ideas for pesticide resistance management. Although several studies have unveiled the positive or negative impacts of gut microbes on host pesticide resistance, minimal research is available regarding the association between gut microbes and host phosphine resistance. To explore the influence of gut bacteria on host phosphine susceptibility and its molecular basis, mortality, fitness, redox responses, and immune responses of adult <i>Tribolium castaneum</i> were determined when it was challenged by phosphine exposure and/or gut bacteria inoculation. Five cultivable gut bacteria were excised from a population of phosphine-resistant <i>T</i>. <i>castaneum</i>. Among them, only <i>Enterococcus</i> sp. inoculation significantly promoted host susceptibility to phosphine, while inoculation of any other gut bacteria had no significant effect on host phosphine susceptibility. Furthermore, when <i>T</i>. <i>castaneum</i> was exposed to phosphine, <i>Enterococcus</i> sp. inoculation decreased the female fecundity, promoted host oxidative stress, and suppressed the expression and activity of host superoxide dismutase, catalase, and peroxidase. In the absence of phosphine, <i>Enterococcus</i> sp. inoculation also elicited overactive immune responses in <i>T</i>. <i>castaneum</i>, including the immune deficiency and Toll signaling pathways and the dual oxidase–reactive oxygen species system. These results indicate that <i>Enterococcus</i> sp. likely promotes host phosphine susceptibility by aggravating oxidative stress and fitness costs.
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