期刊
ACS MEDICINAL CHEMISTRY LETTERS
卷 3, 期 8, 页码 668-672出版社
AMER CHEMICAL SOC
DOI: 10.1021/ml300128f
关键词
antibiotics; metalloprotease inhibitors; virulence factors; hydroxypyridinthiones
资金
- NIH [R01 AI077644, R01 GM098435]
Bacterial resistance coupled to our current arsenal of antibiotics presents us with a growing threat to public health, thus warranting the exploration of alternative antibacterial strategies. In particular, the targeting of virulence factors has been regarded as a second generation antibiotic approach. In Pseudomonas aeruginosa, a Zn2+ metalloprotease virulence factor, LasB or P. aeruginosa elastase, has been implicated in the development of P. aeruginosa-related keratitis, pneumonia, and burn infection. Moreover, the enzyme also plays a critical role in swarming and biofilm formation, both of which are processes that have been linked to antibiotic resistance. To further validate the importance of LasB in P. aeruginosa infection, we describe our efforts toward the discovery of nonpeptidic small molecule inhibitors of LasB. Using identified compounds, we have confirmed the role that LasB plays in P. aeruginosa swarming and demonstrate the potential for LasB-targeted small molecules in studying antimicrobial-resistant P. aeruginosa phenotypes.
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