Biology subjects

Teng, C.-H.

Publications and source records attributed to Teng, C.-H..

2 recordsLinked to original sources

bioRxiv2023

Quinoclamine inhibits Shiga toxin production in enterohemorrhagic Escherichia coli

ObjectivesEnterohemorrhagic Escherichia coli (EHEC) is responsible for the most severe symptoms of E. coli infections, including hemorrhagic colitis and hemorrhagic uremic syndrome. Shiga toxin 2 (Stx2) plays a significant role as a major virulence factor. The genes encoding Stx2 locate in lambda-like prophage on the EHEC genome. Consequently, Stx2 is expressed when production of the phage is induced by the SOS response. Antibiotic treatment is not recommended for curing the bacterial infection, because it is associated with severe hemorrhagic uremic syndrome. If Stx2 production is prevented, EHEC pathogenicity significantly decreases, and antibiotics may be available to treat the infection. MethodsWe conducted two independent screenings to identify Stx2 production inhibitors for libraries from the RIKEN Natural Product Depository (NPDepo); namely, screening of the Authentic Library, and two-round screening of the Pilot and Analog Libraries. ResultsThe screening of Authentic Library identified niclosamide as a Stx2 production inhibitor. Besides, two naphthoquinoids were identified after the two-round of screening of the Pilot and Analog Libraries. Niclosamide, and quinoclamine, which has structure shared in the two naphthoquinoids, prevented cell lysis via the phage production and ceased Stx2 production in EHEC. The SOS reporter assay indicated that quinoclamine prevented the SOS response in E. coli, whereas niclosamide did not. ConclusionsThese findings suggest that quinoclamine inhibited Stx2 production by preventing the SOS response, whereas niclosamide was involved in phage propagation following the SOS response. These compounds can be a potential therapeutic option to treat EHEC infections.

microbiology↗

bioRxiv2019

Pathogenicity of urinary tract infection Escherichia coli in Caenorhabditis elegans

Uropathogenic Escherichia coli (UPEC) is a major bacterial pathogen that causes urinary tract infections (UTIs). Several virulence factors (VFs) in the bacteria have been associated with the pathogenicity. The mouse is an available UTI model for studying the pathogenicity; however, Caenorhabditis elegans represents as an alternative surrogate host for studying UPEC with the capacity for high-throughput analysis. Therefore, we established a simple assay for a UPEC infection model with C. elegans for large-scale screening. An E. coli culture to be tested and synchronized C. elegans were mixed in 96-well plates, and the pathogenicity was determined by comparison of the turbidity before and after incubation. A total of 133 clinically isolated E. coli strains, which included UTI-associated and fecal isolates, were applied to demonstrate the liquid pathogenicity assay. The E. coli isolates associated with UTIs showed higher pathogenicity in C. elegans than the fecal isolates, suggesting that the simple assay with C. elegans is useful as a UPEC infectious model. From the screening, VFs involved with iron acquisition (chuA, fyuA, and irp2) were significantly associated with high pathogenicity. C. elegans is a heme auxotroph, and iron homeostasis also serves innate immunity in C. elegans. We then evaluated whether the VFs in UPEC were involved in the pathogenicity. Mutants of E. coli UTI89 with defective iron acquisition systems were applied to a solid killing assay with C. elegans. As a result, the survival rate of C. elegans fed with the mutants significantly increased compared to when fed with the parent strain. To our knowledge, this is the first report of the involvement of iron acquisition in the pathogenicity of UPEC in a C. elegans model.

microbiology↗