Journal of Microbiology

Journal Article

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; 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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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.

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Research Support, Non-U.S. Gov't

Note] Identification of High-Specificity H-NS Binding Site in LEE5 Promoter of Enteropathogenic Esherichia coli (EPEC): Abhay Prasad Bhat , Minsang Shin , Hyon E. Choy; J. Microbiol. 2014;52(7):626-629. Published online March 7, 2014; DOI: https://doi.org/10.1007/s12275-014-3562-x

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Abstract

Histone-like nucleoid structuring protein (H-NS) is a small but abundant protein present in enteric bacteria and is involved in compaction of the DNA and regulation of the transcription. Recent reports have suggested that H-NS binds to a specific AT rich DNA sequence than to intrinsically curved DNA in sequence independent manner. We detected two high-specificity H-NS binding sites in LEE5 promoter of EPEC centered at -110 and -138, which were close to the proposed consensus H-NS binding motif. To identify H-NS binding sequence in LEE5 promoter, we took a random mutagenesis approach and found the mutations at around -138 were specifically defective in the regulation byH-NS. It was concluded that H-NS exertsmaximumrepression via the specific sequence at around -138 and ubsequently contacts α subunit of RNAP through oligomerization.

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Horizontally Acquired Homologs of Xenogeneic Silencers: Modulators of Gene Expression Encoded by Plasmids, Phages and Genomic Islands
Alejandro Piña-Iturbe, Isidora D. Suazo, Guillermo Hoppe-Elsholz, Diego Ulloa-Allendes, Pablo A. González, Alexis M. Kalergis, Susan M. Bueno
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Recent advances in genetic engineering tools based on synthetic biology
Jun Ren, Jingyu Lee, Dokyun Na
Journal of Microbiology.2020; 58(1): 1. CrossRef
Regulation of the Locus of Enterocyte Effacement in Attaching and Effacing Pathogens
R. Christopher D. Furniss, Abigail Clements, William Margolin
Journal of Bacteriology.2018;[Epub] CrossRef
Bacterial-Chromatin Structural Proteins Regulate the Bimodal Expression of the Locus of Enterocyte Effacement (LEE) Pathogenicity Island in Enteropathogenic Escherichia coli
Hervé Leh, Ahmad Khodr, Marie-Christine Bouger, Bianca Sclavi, Sylvie Rimsky, Stéphanie Bury-Moné, Susan Gottesman
mBio.2017;[Epub] CrossRef
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Vedran Milosavljevic, Pavlina Jelinkova, Ana Maria Jimenez Jimenez, Amitava Moulick, Yazan Haddad, Hana Buchtelova, Sona Krizkova, Zbynek Heger, Lukas Kalina, Lukas Richtera, Pavel Kopel, Vojtech Adam
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H-NS and RNA polymerase: a love–hate relationship?
Robert Landick, Joseph T Wade, David C Grainger
Current Opinion in Microbiology.2015; 24: 53. CrossRef
Effect of promoter-upstream sequence on σ38-dependent stationary phase gene transcription
Hyung-Ju Lim, Kwangsoo Kim, Minsang Shin, Jae-Ho Jeong, Phil Youl Ryu, Hyon E. Choy
Journal of Microbiology.2015; 53(4): 250. CrossRef

Role of chromatin structure in HMRE mediated transcriptional repression of the HSP82 heat shock gene: Lee, See Woo , Gross, Davis S.; J. Microbiol. 1996;34(1):40-48.

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Abstract: We have examined the chromatin structure of the HMRE/HSP82 and HMRa/HSP82 allels using three complementary approaches : DNase I chromating footprinting, micrococcal nuclease (MNase) nucleosome-protected ladder assay, and an in vivo E. coli dam methylase accessibility assay. The footprinting results indicate that the promoter and silencer sequences are assembled into nucleoprotein complexes which exhibit no detectable change in structure, despite a 70-fold range in expression levels. In addition, the promoter region of the HMRa/HSP82 allele is cleaved randomly by MNase in all cases, indicating the absence of anonical nucleosomes over this region irrespective of SIR4 or heat-shock. Finally, no discernible difference in the accessibility of the HMRE/HSP82 locus to dam methylase in SIR4 vs. sir4 cells was seen, which again suggests that the chromatin structure of HMRE/HSP82 allele is identical regardless of SIR4. Altogether, our results indicate that in contrast to other observations of the silent mating-type loci, no discernible structural alteration is detected at either HMR/HSP82 allele regardless of SIR genetic background or transcriptional state of the gene.

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