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.