Few reports on tachyplesin I drug-resistence, and its recombination large-scale production has not been realized.As a cationic antimicrobial peptide, tachyplesin I demostrates potent and rapid activities against gram positive bacteria, gram negative bacteria, fungi, viruses, protozoa, microalgae, tumor and cancer cells, which promises great prospects for research and development of tachyplesin I in animal husbandry, food industry, pharmaceutical industry and environment protection.However, it leaves much room to be improved as far as commercialization of gene recombinant tachyplesin I is concerned.Mutual destruction between tachyplesin I and host cells has been a bottle-neck, hindering the efficient expression of gene of tachyplesin I.For example, previous research conducted by our team indicates that tachyplesin I is not compatible with its host with rather low production of tachyplesin I could be expressed by feed-grade Bacillus subtilis both Bs168 and Wb800 (Bs168 of eight protease gene deficient type) by means of secretion.Therefore, obtaining an appropriate host cell capable of enduring high concentration of tachyplesin I without degrading tachyplesin I is of great importance.In order to construct such an appropriate host cell capable of enduring high concentration of tachyplesin I without degrading tachyplesin I, both forage Bacillus subtilis Bs168 and Wb800 strains of high anti-tachyplesin I were obtained by long-term stress of tachyplesin I.Multiple omics technology were utilized to analyze the molecular basis in the new two strains to adapt to long-term stress of tachyplesin I.In Bs168 of high anti-tachyplesin I, transcription of six genes of aprE, bpr, △vpr, wprA, ywaD and ypwA rise significantly, which resulted in six kinds of corresponding proteolytic enzymes presented in proteome.And in Wb800 of high anti-tachyplesin I, transcription of two genes of ywaD and ypwA increased significantly, which resulted in two kinds of corresponding proteolytic enzymes levels improved significantly in proteome.It is suggested that six kinds of proteolytic enzymes (aprE, bpr, △vpr, wprA,ywaD andypwA) might help forage B.subtilis adapt to long-term stress oftachyplesin I.