Objective Earlier, we have found that the enteropathogenicYersinia enterocoliticahave evolved the survival mechanisms that regulate the expression of laccase-encoding genes in the gut. The present study aims to characterize the purified recombinant laccase fromY. enterocoliticastrain 8081 biovar 1B and understand its effect on the midgut of cotton bollworm,Helicoverpa armigera(Hubner) larvae. Results The recombinant laccase protein showed high purity fold and low molecular mass (similar to 43 kDa).H. armigeralarvae fed with laccase protein showed a significant decrease in body weight and damage in the midgut. Further, transmission electron microscopy (TEM) studies revealed the negative effect of laccase protein on trachea, malpighian tubules, and villi of the insect. The proteome comparison between control and laccase-fed larvae of cotton bollworm showed significant expression of proteolytic enzymes, oxidoreductases, cytoskeletal proteins, ribosomal proteins; and proteins for citrate (TCA cycle) cycle, glycolysis, stress response, cell redox homeostasis, xenobiotic degradation, and insect defence. Moreover, it also resulted in the reduction of antioxidants, increased melanization (insect innate immune response), and enhanced free radical generation. Conclusions All these data collectively suggest thatH. armigera(Hubner) larvae can be used to study the effect of microbes and their metabolites on the host physiology, anatomy, and survival. [GRAPHICS] .