title: Studies of Antibiotic Resistance of Beta-Lactamase Bacteria under Different Nutrition Limitations at the Single-Cell Level.
abstract: Drug resistance involves many biological processes, including cell growth, cell communication, and cell cooperation. In the last few decades, bacterial drug resistance studies have made substantial progress. However, a major limitation of the traditional resistance study still exists: most of the studies have concentrated on the average behavior of enormous amounts of cells rather than surveying single cells with different phenotypes or genotypes. Here, we report our study of beta-lactamase bacterial drug resistance in a well-designed microfluidic device, which allows us to conduct more controllable experiments, such as controlling the nutrient concentration, switching the culture media, performing parallel experiments, observing single cells, and acquiring time-lapse images. By using GFP as a beta-lactamase indicator and acquiring time-lapse images at the single-cell level, we observed correlations between the bacterial heterogeneous phenotypes and their behavior in different culture media. The feedback loop between the growth rate and the beta-lactamase production suggests that the beta-lactamase bacteria are more resistant in a rich medium than in a relatively poor medium. In the poorest medium, the proportion of dormant cells may increase, which causes a lower death rate in the same generation. Our work may contribute to assaying the antibiotic resistance of pathogenic bacteria in heterogeneous complex media.
authors.affiliation: The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Ran
authors.affiliation: Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, China; Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ouyang
authors.affiliation: The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, China; Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
authors.forename: Chunxiong
authors.initials: C
authors.lastname: Luo
mesh_terms: D001419:Bacteria / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D003470:Culture Media / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D005453:Fluorescence; D007091:Image Processing, Computer-Assisted; D050296:Microbial Viability / Q000187:drug effects; D010641:Phenotype; D059010:Single-Cell Analysis; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D003470:Culture Media; D001618:beta-Lactamases