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Open AccessArticle

Specific NDM-1 Inhibitor of Isoliquiritin Enhances the Activity of Meropenem against NDM-1-positive Enterobacteriaceae in vitro

1
College of Animal Science, Jilin University, Changchun 130062, Jilin, China
2
Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China
3
Qingdao Vland biological Limited co., LTD., Qingdao 266000, China
4
College of Veterinary Medicine, Xinjiang Agricultural University, Urmuqi 830052, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Environ. Res. Public Health 2020, 17(6), 2162; https://doi.org/10.3390/ijerph17062162 (registering DOI)
Received: 17 January 2020 / Revised: 23 March 2020 / Accepted: 23 March 2020 / Published: 24 March 2020
(This article belongs to the Section Environmental Microbiology)
NDM-1-positive Enterobacteriaceae have caused serious clinical infections, with high mortality rates. Carbapenem was the ultimate expectation for the treatment of such infections in clinical practice. However, since the discovery of plasmid-mediated New Delhi metallo-β-lactamase-1 (NDM-1), the efficient therapeutic effects of carbapenems have been increasingly restricted. Here, we identified isoliquiritin, a novel specific inhibitor of the NDM-1 enzyme that restored the activity of carbapenem against NDM-1-producing E. coli isolates and K. pneumoniae isolates without affecting the growth of bacteria. A checkerboard test, growth curve assays and time-kill assays confirmed the significant synergistic effect of isoliquiritin combined with meropenem in vitro. It is worth noting that isoliquiritin only inhibited the activity of NDM-1 and had no obvious inhibitory effect on other class B metallo-β-lactamases (VIM-1) or NDM-1 mutants (NDM-5). The FIC indices of meropenem with isoliquiritin on NDM-1-positive E. coli and K. pneumoniae were all less than 0.5. Isoliquiritin had no influences on the expression of NDM-1-positive strains at concentrations below 64 µg/mL. Collectively, our results show that isoliquiritin is a potential adjuvant therapy drug that could enhance the antibacterial effect of carbapenems, such as meropenem, on NDM-1-positive Enterobacteria and lay the foundation for subsequent clinical trials. View Full-Text
Keywords: NDM-1 inhibitor; isoliquiritin; meropenem; Enterobacteriaceae NDM-1 inhibitor; isoliquiritin; meropenem; Enterobacteriaceae
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Wang, Y.; Sun, X.; Kong, F.; Xia, L.; Deng, X.; Wang, D.; Wang, J. Specific NDM-1 Inhibitor of Isoliquiritin Enhances the Activity of Meropenem against NDM-1-positive Enterobacteriaceae in vitro. Int. J. Environ. Res. Public Health 2020, 17, 2162.

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