Publications by authors named "Eun-Ik Koh"
Successful tuberculosis therapy requires treatment with an unwieldy multidrug combination for several months. Thus, there is a growing need to identify novel genetic vulnerabilities that can be leveraged to develop new, more effective antitubercular drugs. Consequently, recent efforts to optimize tuberculosis (TB) therapy have exploited (Mtb) chemical genetics to identify pathways influencing antibiotic efficacy, novel mechanisms of antibiotic action, and new targets for TB drug discovery.
View Article and Find Full Text PDFUnlabelled: Successful tuberculosis therapy requires treatment with an unwieldy multidrug combination for several months. Thus, there is a growing need to identify novel genetic vulnerabilities that can be leveraged to develop new, more effective antitubercular drugs. Consequently, recent efforts to optimize TB therapy have exploited Mtb chemical genetics to identify pathways influencing antibiotic efficacy, novel mechanisms of antibiotic action, and new targets for TB drug discovery.
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- * This study explored the relationship between Mtb's carbon metabolism and drug interactions by using gene knockdown mutants to analyze the effects of common antitubercular drugs, revealing that the bacterial metabolic state significantly influences drug efficacy.
- * The researchers identified ways to enhance rifampicin effectiveness when Mtb grows on cholesterol, providing insights that could help improve drug combinations and understanding of how laboratory results relate to real-world infection scenarios.
Article Synopsis
- - The text discusses chemical-genetics (C-G) experiments that identify the interactions between bacterial genes and inhibitory compounds, helping to reveal drug targets and related pathways by using a library of modified strains.
- - The methodology includes treating these strains with drugs and using high-throughput sequencing to measure how the relative abundance of different mutants changes, relying on the idea that specific genes may show greater fitness loss when exposed to both the drug and reduced protein levels.
- - A new statistical method called CGA-LMM is introduced to analyze data from C-G experiments more effectively, focusing on how gene abundance varies with drug concentration, and it has successfully identified known target genes in M. tuberculosis for most of the tested antibiotics.
Article Synopsis
- TB treatment is complicated by the need for long-term drug administration and the emergence of drug-resistant strains, which prompted a genetic study to identify bacterial genes affecting treatment efficacy.
- Researchers discovered several bacterial genes, particularly one related to glycerol catabolism, that influence antibiotic sensitivity and contribute to the survival of bacteria during treatment.
- The study also revealed that mutations in a specific gene region are linked to multidrug resistance, suggesting that variations in metabolic processes can lead to drug-tolerant bacterial clones and affect TB control efforts.
Invasive Gram-negative bacteria often express multiple virulence-associated metal ion chelators to combat host-mediated metal deficiencies. , , and isolates encoding the high pathogenicity island (HPI) secrete yersiniabactin (Ybt), a metallophore originally shown to chelate iron ions during infection. However, our recent demonstration that Ybt also scavenges copper ions during infection led us to question whether it might be capable of retrieving other metals as well.
View Article and Find Full Text PDFCopper plays a dual role as a nutrient and a toxin during bacterial infections. While uropathogenic Escherichia coli (UPEC) strains can use the copper-binding metallophore yersiniabactin (Ybt) to resist copper toxicity, Ybt also converts bioavailable copper to Cu(II)-Ybt in low-copper conditions. Although E.
View Article and Find Full Text PDFThe Yersinia high-pathogenicity island (HPI) is common to multiple virulence strategies used by Escherichia coli strains associated with urinary tract infection (UTI). Among the genes in this island are ybtP and ybtQ, encoding distinctive ATP binding cassette (ABC) proteins associated with iron(III)-yersiniabactin import in Yersinia pestis In this study, we compared the impact of ybtPQ on a model E. coli cystitis strain during in vitro culture and experimental murine infections.
View Article and Find Full Text PDFNumerous pathogenic microorganisms secrete small molecule chelators called siderophores defined by their ability to bind extracellular ferric iron, making it bioavailable to microbes. Recently, a siderophore produced by uropathogenic Escherichia coli, yersiniabactin, was found to also bind copper ions during human infections. The ability of yersiniabactin to protect E.
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- Uropathogenic Escherichia coli produce siderophores, like yersiniabactin, which help them acquire metals during urinary tract infections, notably binding to copper ions as well as iron.
- A mass spectrometric study revealed that yersiniabactin forms stable complexes with various metals, including nickel, cobalt, and chromium, in addition to iron and copper.
- The outer membrane importer FyuA facilitates the uptake of these metal complexes in a TonB-dependent manner, with copper(II)-yersiniabactin being structurally unique and not inhibiting the import of iron(III) yersiniabactin.
The Streptococcus pyogenes NAD(+) glycohydrolase (SPN) is secreted from the bacterial cell and translocated into the host cell cytosol where it contributes to cell death. Recent studies suggest that SPN is evolving and has diverged into NAD(+) glycohydrolase-inactive variants that correlate with tissue tropism. However, the role of SPN in both cytotoxicity and niche selection are unknown.
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