Screening of small molecules attenuating biofilm formation of Acinetobacter baumannii by inhibition of ompA promoter activity

Seok Hyeon Na; Hyejin Jeon; Man Hwan Oh; Yoo Jeong Kim; Je Chul Lee

doi:10.1007/s12275-021-1394-z

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Screening of small molecules attenuating biofilm formation of Acinetobacter baumannii by inhibition of ompA promoter activity: Seok Hyeon Na ¹, Hyejin Jeon ², Man Hwan Oh ³, Yoo Jeong Kim ², Je Chul Lee ²; Journal of Microbiology 2021;59(9):871-878.
DOI: https://doi.org/10.1007/s12275-021-1394-z
Published online: August 27, 2021

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

Corresponding author: Je Chul Lee , Tel: +82-53-420-4844,

Received: 21 July 2021 • Revised: 5 August 2021 • Accepted: 5 August 2021

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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.

Keywords: Acinetobacter baumannii, outer membrane protein A, biofilm formation, HTS system, anti-virulence agent

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Screening of small molecules attenuating biofilm formation of Acinetobacter baumannii by inhibition of ompA promoter activity

J. Microbiol. 2021;59(9):871-878. Published online August 27, 2021

DOI: https://doi.org/10.1007/s12275-021-1394-z

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