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In this study, we investigated the adaptive resistance mechanism in <jats:italic>A. hydrophila<\/jats:italic> by multiple proteomic methods. Dimethyl labeling and label-free methods were performed to compare the differential expression of proteins in response to various doses of oxytetracycline (OXY). The results point to the conclusions that, in response to OXY stress, translational processes increase the abundance of these proteins whereas largely central metabolic pathways decrease their abundance. To confirm our hypothesis, various exogenous metabolites were compounded with OXY, and the resulting survival capabilities were measured. Results show that 7 metabolites (malic acid, serine, methionine, etc.) significantly decreased the survival capabilities of <jats:italic>A. hydrophila<\/jats:italic> in the presence of OXY, whereas 4 metabolites (arginine, lysine, tyrosine, etc.) did the opposite. Further investigation suggests that a compound comprising exogenous metabolites in combination with various antibiotics could have a significant bactericidal effect and might come into widespread use, especially together with tetracycline antibiotics. These findings may provide new clues to the antimicrobial treatment of <jats:italic>A. hydrophila<\/jats:italic> infection.<\/jats:p>","DOI":"10.1038\/srep39413","type":"journal-article","created":{"date-parts":[[2016,12,19]],"date-time":"2016-12-19T10:13:54Z","timestamp":1482142434000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Proteomic Analysis Reveals That Metabolic Flows Affect the Susceptibility of Aeromonas hydrophila to Antibiotics"],"prefix":"10.1038","volume":"6","author":[{"given":"Zujie","family":"Yao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feifei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxiong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangmin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,12,19]]},"reference":[{"key":"BFsrep39413_CR1","doi-asserted-by":"publisher","first-page":"2474","DOI":"10.1056\/NEJMp1311479","volume":"369","author":"A Hollis","year":"2013","unstructured":"Hollis, A. & Ahmed, Z. 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