Going on offense against the gram-negative defense
| Autor: | Paul J. Hergenrother, Bryon S. Drown |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Multidisciplinary biology Pseudomonas aeruginosa medicine.drug_class Antibiotics biology.organism_classification medicine.disease_cause medicine.disease Enterobacteriaceae Bacterial cell structure Acinetobacter baumannii Microbiology 03 medical and health sciences 030104 developmental biology medicine Klebsiella pneumonia Escherichia coli Bacteria |
| Zdroj: | Proceedings of the National Academy of Sciences. 115:6530-6532 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1807278115 |
| Popis: | Bacterial infections resistant to antibiotics are becoming more common, posing a significant health risk (1). The CDC and WHO have identified gram-negative drug-resistant pathogens as being particularly dangerous, and such infections are resistant to nearly all available antibiotics in some cases (2, 3). The most concerning of these infections are three classes of nonfastidious gram-negative pathogens, Enterobacteriaceae (including Escherichia coli and Klebsiella pneumonia ), Pseudomonas aeruginosa , and Acinetobacter baumannii . As only nine classes of antibiotics (that engage five targets) are available for the treatment of these infections (4), the need for new classes of antibiotics effective against gram-negative bacteria is self-evident. In PNAS, Zhang et al. (5) present an innovative approach for discovering antibiotics that exploit previously untargeted components of lipopolysaccharide (LPS) biogenesis and use this screening platform to identify a lead compound that inhibits LPS biosynthetic machinery. Historically, there has been a heavy reliance on whole-cell toxicity assays for identification of new antibiotic classes, and, in fact, all classes of US Food and Drug Administration-approved antibiotics were initially discovered in these types of cell culture phenotypic screens (1). Unfortunately, this approach has rarely provided compelling lead compounds with activity against gram-negative bacteria; the quinolones are the most recently introduced class of broad-spectrum antibiotics, over 50 y ago (in 1968) (4). AstraZeneca, GlaxoSmithKline, and others have all published detailed accounts of their independent screening of a combined >8 million compounds in bacterial cell culture death assays; it is sobering to note that these experiments failed to produce any compounds with sufficient gram-negative activity to merit advancement (6⇓⇓–9). While biochemical … [↵][1]1To whom correspondence should be addressed. Email: hergenro{at}illinois.edu. [1]: #xref-corresp-1-1 |
| Databáze: | OpenAIRE |
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