Title |
Screening of small molecules attenuating biofilm formation of Acinetobacter baumannii by inhibition of ompA promoter activity |
Author |
Seok Hyeon Na1, Hyejin Jeon2, Man Hwan Oh3, Yoo Jeong Kim2, and Je Chul Lee2* |
Address |
1Division of Antimicrobial Resistance Research, Center for Infectious Diseases Research, National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju 28159, Republic of Korea, 2Department of Microbiology, School of Medicine, Kyungpook National University, Daegu 41566, Republic of Korea, 3Department of Microbiology, Dankook University, Cheonan 31116, Republic of Korea |
Bibliography |
Journal of Microbiology, 59(9),871-878, 2021,
|
DOI |
10.1007/s12275-021-1394-z
|
Key Words |
Acinetobacter baumannii, outer membrane protein
A, biofilm formation, HTS system, anti-virulence agent |
Abstract |
Anti-virulence therapeutic strategies are promising alternatives
against drug-resistant pathogens. Outer membrane
protein A (OmpA) plays a versatile role in the pathogenesis
and antimicrobial resistance of Acinetobacter baumannii.
Therefore, OmpA is an innovative target for anti-virulence
therapy against A. baumannii. This study aimed to develop
a high-throughput screening (HTS) system to discover small
molecules inhibiting the ompA promoter activity of A. baumannii
and screen chemical compounds using the bacterial
growth-based HTS system. The ompA promoter and open
reading frame of nptI fusion plasmids that controlled the
expression of nptI encoding resistance to kanamycin by the
ompA promoter were constructed and then transformed into
A. baumannii ATCC 17978. This reporter strain was applied
to screen small molecules inhibiting the ompA promoter
activity in a chemical library. Of the 7,520 chemical compounds,
15 exhibited ≥ 70% growth inhibition of the report
strain cultured in media containing kanamycin. Three compounds
inhibited the expression of ompA and OmpA in the
outer membrane of A. baumannii ATCC 17978, which subsequently
reduced biofilm formation. In conclusion, our reporter
strain is useful for large-scale screening of small molecules
inhibiting the ompA expression in A. baumannii. Hit
compounds identified by the HTS system are promising scaffolds
to develop novel therapeutics against A. baumannii. |