title: In vivoHost Environment AltersPseudomonas aeruginosaSusceptibility to Aminoglycoside Antibiotics.
abstract: During host infection,Pseudomonas aeruginosacoordinately regulates the expression of numerous genes to adapt to the host environment while counteracting host clearance mechanisms. As infected patients take antibiotics, the invading bacteria encounter antibiotics in the host milieu.P. aeruginosais highly resistant to antibiotics due to multiple chromosomally encoded resistant determinants. And numerousin vitrostudies have demonstrated the regulatory mechanisms of antibiotic resistance related genes in response to antibiotics. However, it is not well-known how host environment affects bacterial response to antibiotics. In this study, we found thatP. aeruginosacells directly isolated from mice lungs displayed higher susceptibility to tobramycin thanin vitrocultured bacteria.In vitroexperiments demonstrated that incubation with A549 and differentiated HL60 (dHL60) cells sensitizedP. aeruginosato tobramycin. Further studies revealed that reactive oxygen species produced by the host cells contributed to the increased bacterial susceptibility. At the same concentration of tobramycin, presence of A549 and dHL60 cells resulted in higher expression of heat shock proteins, which are known inducible by tobramycin. Further analyses revealed decreased membrane potential upon incubation with the host cells and modification of lipopolysaccharide, which contributed to the increased susceptibility to tobramycin. Therefore, our results demonstrate that contact with host cells increased bacterial susceptibility to tobramycin.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University Tianjin, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University Tianjin, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University Tianjin, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University Tianjin, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University Tianjin, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University Tianjin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy and Life Sciences, Nankai University Tianjin, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University Tianjin, China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University Tianjin, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai UniversityTianjin, China; Department of Molecular Genetics and Microbiology, College of Medicine, University of FloridaGainesville, FL, USA.
authors.forename: Shouguang
authors.initials: S
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University Tianjin, China.
authors.forename: Weihui
authors.initials: W
authors.lastname: Wu
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D008168:Lung / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000032:analysis; D014031:Tobramycin / Q000494:pharmacology
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D017382:Reactive Oxygen Species; D014031:Tobramycin
keywords: Pseudomonas aeruginosa; host cells; infection; membrane potential; neutrophil; tobramycin