Discovery of Antimicrobial Agents Based on Structural and Functional Study of the <i>Klebsiella pneumoniae</i> MazEF Toxin-Antitoxin System

<i>Klebsiella pneumoniae</i> causes severe human diseases, but its resistance to current antibiotics is increasing. Therefore, new antibiotics to eradicate <i>K. pneumoniae</i> are urgently needed. Bacterial toxin-antitoxin (TA) systems are strongly correlated with physiologi...

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Main Authors: Chenglong Jin (Author), Sung-Min Kang (Author), Do-Hee Kim (Author), Yuno Lee (Author), Bong-Jin Lee (Author)
Format: Book
Published: MDPI AG, 2024-04-01T00:00:00Z.
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Summary:<i>Klebsiella pneumoniae</i> causes severe human diseases, but its resistance to current antibiotics is increasing. Therefore, new antibiotics to eradicate <i>K. pneumoniae</i> are urgently needed. Bacterial toxin-antitoxin (TA) systems are strongly correlated with physiological processes in pathogenic bacteria, such as growth arrest, survival, and apoptosis. By using structural information, we could design the peptides and small-molecule compounds that can disrupt the binding between <i>K. pneumoniae</i> MazE and MazF, which release free MazF toxin. Because the MazEF system is closely implicated in programmed cell death, artificial activation of MazF can promote cell death of <i>K. pneumoniae</i>. The effectiveness of a discovered small-molecule compound in bacterial cell killing was confirmed through flow cytometry analysis. Our findings can contribute to understanding the bacterial MazEF TA system and developing antimicrobial agents for treating drug-resistant <i>K. pneumoniae</i>.
Item Description:10.3390/antibiotics13050398
2079-6382