Synchrotron-Based X-Ray Fluorescence Microscopy Reveals Accumulation of Polymyxins in Single Human Alveolar Epithelial Cells
Mohamad AK Azad, Shuo Zhang, Jiayao Li, Yeonuk Kim, Heidi H Yu, Alex J Fulcher, Daryl L Howard, Martin D de Jonge, Simon A James, Kade D Roberts, Tony Velkov, Jing Fu, Qi Tony Zhou, Jian Li
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | AMER SOC MICROBIOLOGY | Published : 2021
Intravenous administration of the last-line polymyxins results in poor drug exposure in the lungs and potential nephrotoxicity; while inhalation therapy offers better pharmacokinetics/pharmacodynamics for pulmonary infections by delivering the antibiotic to the infection site directly. However, polymyxin inhalation therapy has not been optimized and adverse effects can occur. This study aimed to quantitatively determine the intracellular accumulation and distribution of polymyxins in single human alveolar epithelial A549 cells. Cells were treated with an iodine-labeled polymyxin probe FADDI-096 (5.0 and 10.0 μM) for 1, 4, and 24 h. Concentrations of FADDI-096 in single A549 cells were determ..View full abstract
Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH)
Awarded by Australian National Health and Medical Research Council (NHMRC)
This study was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH; grants R01 AI132681 and R01 AI146160) and the Australian National Health and Medical Research Council (NHMRC; grant APP1104581). J.L. is an NHMRC Principal Research Fellow and T.V. is an NHMRC Industry Career Development Fellow.