High-Resolution Bacterial Cytological Profiling Reveals Intrapopulation Morphological Variations upon Antibiotic Exposure
Issued Date
2023-02-01
Resource Type
ISSN
00664804
eISSN
10986596
Scopus ID
2-s2.0-85148240410
Pubmed ID
36625642
Journal Title
Antimicrobial Agents and Chemotherapy
Volume
67
Issue
2
Rights Holder(s)
SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy Vol.67 No.2 (2023)
Suggested Citation
Samernate T., Htoo H.H., Sugie J., Chavasiri W., Pogliano J., Chaikeeratisak V., Nonejuie P. High-Resolution Bacterial Cytological Profiling Reveals Intrapopulation Morphological Variations upon Antibiotic Exposure. Antimicrobial Agents and Chemotherapy Vol.67 No.2 (2023). doi:10.1128/aac.01307-22 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82425
Title
High-Resolution Bacterial Cytological Profiling Reveals Intrapopulation Morphological Variations upon Antibiotic Exposure
Other Contributor(s)
Abstract
Phenotypic heterogeneity is crucial to bacterial survival and could provide insights into the mechanism of action (MOA) of antibiotics, especially those with poly-pharmacological actions. Although phenotypic changes among individual cells could be detected by existing profiling methods, due to the data complexity, only population average data were commonly used, thereby overlooking the heterogeneity. In this study, we developed a high-resolution bacterial cytological profiling method that can capture morphological variations of bacteria upon antibiotic treatment. With an unprecedented single-cell resolution, this method classifies morphological changes of individual cells into known MOAs with an overall accuracy above 90%. We next showed that combinations of two antibiotics induce altered cell morphologies that are either unique or similar to that of an antibiotic in the combinations. With these combinatorial profiles, this method successfully revealed multiple cytological changes caused by a natural product-derived compound that, by itself, is inactive against Acinetobacter baumannii but synergistically exerts its multiple antibacterial activities in the presence of colistin. The findings have paved the way for future single-cell profiling in bacteria and have highlighted previously underappreciated intrapopulation variations caused by antibiotic perturbation.