title: Myo-inositol improves the host's ability to eliminate balofloxacin-resistant Escherichia coli.
abstract: Antibiotic-resistant mechanisms are associated with fitness costs. However, why antibiotic-resistant bacteria usually show increasing adaptation to hosts is largely unknown, especially from the host's perspective. The present study reveals the host's varied response to balofloxacin-resistant Escherichia coli (BLFX-R) using an integrated proteome and metabolome approach and identifies myo-inositol and phagocytosis-related proteins as crucial biomarkers. Originally, macrophages have an optimal attractive preference to BLFX-S due to more polarization of BLFX-S than BLFX-R, which renders faster elimination to BLFX-S than BLFX-R. The slower elimination to BLFX-R may be reversed by exogenous myo-inositol. Primarily, myo-inositol depolarizes macrophages, elevating adherence to both BLFX-S and BLFX-R. Since the altered adherence is equal to both strains, the myo-inositol-treated macrophages are free of the barrier to BLFX-R and thereby promote phagocytosis of BLFX-R. This work provides a novel strategy based on metabolic modulation for eliminating antibiotic-resistant bacteria with a high degree of host adaptation.
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Bio-Control, MOE Key Lab Aquat Food Safety, School of Life Sciences, Sun Yat-sen University, University City, Guangzhou 510006, People's Republic of China.
authors.forename: Xin-Hai
authors.initials: XH
authors.lastname: Chen
authors.affiliation: 1] Center for Proteomics and Metabolomics, State Key Laboratory of Bio-Control, MOE Key Lab Aquat Food Safety, School of Life Sciences, Sun Yat-sen University, University City, Guangzhou 510006, People's Republic of China [2] Drug Discovery Pipeline, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, Guangdong, People's Republic of China.
authors.forename: Bing-Wen
authors.initials: BW
authors.lastname: Zhang
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Bio-Control, MOE Key Lab Aquat Food Safety, School of Life Sciences, Sun Yat-sen University, University City, Guangzhou 510006, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Bio-Control, MOE Key Lab Aquat Food Safety, School of Life Sciences, Sun Yat-sen University, University City, Guangzhou 510006, People's Republic of China.
authors.forename: Xuan-Xian
authors.initials: XX
authors.lastname: Peng
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015415:Biomarkers; D019295:Computational Biology / Q000379:methods; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000378:metabolism* / Q000382:microbiology*; D024841:Fluoroquinolones / Q000494:pharmacology*; D054884:Host-Pathogen Interactions; D007294:Inositol / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008954:Models, Biological; D010587:Phagocytosis / Q000276:immunology; D040901:Proteomics / Q000379:methods; D015027:Zebrafish
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D024841:Fluoroquinolones; D007294:Inositol; C077155:balofloxacin