Publication: Bacterial Cytological Profiling as a Tool To Study Mechanisms of Action of Antibiotics That Are Active against Acinetobacter baumannii
2
Issued Date
2019-04-01
Resource Type
ISSN
10986596
00664804
00664804
Other identifier(s)
2-s2.0-85063612049
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.63, No.4 (2019)
Suggested Citation
Htut Htut Htoo, Lauren Brumage, Vorrapon Chaikeeratisak, Hannah Tsunemoto, Joseph Sugie, Chanwit Tribuddharat, Joe Pogliano, Poochit Nonejuie Bacterial Cytological Profiling as a Tool To Study Mechanisms of Action of Antibiotics That Are Active against Acinetobacter baumannii. Antimicrobial Agents and Chemotherapy. Vol.63, No.4 (2019). doi:10.1128/AAC.02310-18 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/51773
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Title
Bacterial Cytological Profiling as a Tool To Study Mechanisms of Action of Antibiotics That Are Active against Acinetobacter baumannii
Abstract
Copyright © 2019 American Society for Microbiology. All Rights Reserved. An increasing number of multidrug-resistant Acinetobacter baumannii (MDR-AB) infections have been reported worldwide, posing a threat to public health. The establishment of methods to elucidate the mechanism of action (MOA) of A. baumannii-specific antibiotics is needed to develop novel antimicrobial therapeutics with activity against MDR-AB. We previously developed bacterial cytological profiling (BCP) to understand the MOA of compounds in Escherichia coli and Bacillus subtilis. Given how distantly related A. baumannii is to these species, it was unclear to what extent it could be applied. Here, we implemented BCP as an antibiotic MOA discovery platform for A. baumannii. We found that the BCP platform can distinguish among six major antibiotic classes and can also subclassify antibiotics that inhibit the same cellular pathway but have different molecular targets. We used BCP to show that the compound NSC145612 inhibits the growth of A. baumannii via targeting RNA transcription. We confirmed this result by isolating and characterizing resistant mutants with mutations in the rpoB gene. Altogether, we conclude that BCP provides a useful tool for MOA studies of antibacterial compounds that are active against A. baumannii.