Single Cell Analysis of Drug Susceptibility of Mycobacterium Abscessus During Macrophage Infection

is an emerging health risk to immunocompromised individuals and to people with pre-existing pulmonary conditions. As possesses multiple mechanisms of drug resistance, treatments of are of poor efficacy. Therefore, there is an urgent need for new therapeutic strategies targeting . We describe an expe...

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Bibliographic Details
Published in:Antibiotics (Basel) 2020-10, Vol.9 (10), p.711
Main Authors: Brzostek, Joanna, Fatin, Amierah, Chua, Wen Hui, Tan, Hui Yi, Dick, Thomas, Gascoigne, Nicholas R J
Format: Article
Language:English
Subjects:
Amikacin
Antibiotics
Antiinfectives and antibacterials
Antimicrobial activity
Bacteria
Cell size
Cell viability
Clarithromycin
Control
Drug discovery
Drug resistance
drug screen
Flow cytometry
Gene expression
Health risks
Heterogeneity
Infections
Intracellular
Macrophages
Methods
Mycobacteria
Mycobacterium
Mycobacterium abscessus
Observations
Population
single cell analysis
Tuberculosis
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Summary:is an emerging health risk to immunocompromised individuals and to people with pre-existing pulmonary conditions. As possesses multiple mechanisms of drug resistance, treatments of are of poor efficacy. Therefore, there is an urgent need for new therapeutic strategies targeting . We describe an experimental system for screening of compounds for their antimicrobial activity against intracellular using flow cytometry and imaging flow cytometry. The assay allows simultaneous analysis of multiple parameters, such as proportion of infected host cells, bacterial load per host cell from the infected population, and host cell viability. We verified the suitability of this method using two antibiotics with known activity against : clarithromycin and amikacin. Our analysis revealed a high degree of infection heterogeneity, which correlated with host cell size. A higher proportion of the larger host cells is infected with as compared to smaller host cells, and infected larger cells have higher intracellular bacterial burden than infected smaller cells. Clarithromycin treatment has a more pronounced effect on smaller host cells than on bigger host cells, suggesting that heterogeneity within the host cell population has an effect on antibiotic susceptibility of intracellular bacteria.
ISSN:2079-6382
2079-6382
DOI:10.3390/antibiotics9100711