Journal
ANALYTICAL CHEMISTRY
Volume 92, Issue 21, Pages 14459-14465Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.0c02489
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Funding
- NIH [R01AI141439, R35GM136223, R42CA224844, R44EB027018]
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We report rapid and sensitive phenotyping of bacterial response to antibiotic treatment at single-cell resolution by a Raman-integrated optical mid-infrared photothermal (MIP) microscope. The MIP microscope successfully detected biochemical changes of bacteria in specific to the acting mechanism of erythromycin with 1 h incubation. Compared to Raman spectroscopy, MIP spectroscopy showed a much larger signal-to-noise ratio at the fingerprint region at an acquisition speed as fast as 1 s per spectrum. The high sensitivity of MIP enabled detection of metabolic changes at antibiotic concentrations below minimum inhibitory concentration (MIC). Meanwhile, the single-cell resolution of the technique allowed observation of heteroresistance within one bacterial population, which is of great clinical relevance. This study showcases characterizing antibiotic response as one of the many possibilities of applying MIP microscopy to single-cell biology.
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