statistical metamodeling for revealing synergistic antimicrobial interactions统计元建模揭示协同抗菌作用.pdfVIP

Statistical Metamodeling for Revealing Synergistic Antimicrobial Interactions 1 2 3 4 5 1,6 Chia Hsiang Chen , Vincent Gau , Donna D. Zhang , Joseph C. Liao , Fei-Yue Wang , Pak Kin Wong * 1 Department of Aerospace and Mechanical Engineering, University of Arizona, Tucson, Arizona, United States of America, 2 GeneFluidics Inc., Monterey Park, California, United States of America, 3 Department of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona, United States of America, 4 Department of Urology, Stanford University, Stanford, California, United States of America, 5 The Key Laboratory for Complex Systems and Intelligence Science, The Institute of Automation, Chinese Academy of Sciences, Beijing, China, 6 Biomedical Engineering and Bio5 Institute, University of Arizona, Tucson, Arizona, United States of America Abstract Many bacterial pathogens are becoming drug resistant faster than we can develop new antimicrobials. To address this threat in public health, a metamodel antimicrobial cocktail optimization (MACO) scheme is demonstrated for rapid screening of potent antibiotic cocktails using uropathogenic clinical isolates as model systems. With the MACO scheme, only 18 parallel trials were required to determine a potent antimicrobial cocktail out of hundreds of possible combinations. In particular, trimethoprim and gentamicin were identified to work synergistically for inhibiting the bacterial growth. Sensitivity analysis indicated gentamicin functions as a synergist for trimethoprim, and reduces its minimum inhibitory concentration for 40-fold. Validatio