Journal ArticleDOI
Ten Years with New Delhi Metallo-β-lactamase-1 (NDM-1): From Structural Insights to Inhibitor Design.
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TLDR
The studies dedicated to the design and development of effective NDM-1 inhibitors are reported: the discussion for each agent moves from the employed design strategy to the ability of the identified inhibitor to synergize β-lactam antibiotics.Abstract:
The worldwide emergence of New Delhi metallo-β-lactamase-1 (NDM-1) as a carbapenemase able to hydrolyze nearly all available β-lactam antibiotics has characterized the past decade, endangering efficacious antibacterial treatments. No inhibitors for NDM-1 are available in therapy, nor are promising compounds in the pipeline for future NDM-1 inhibitors. We report the studies dedicated to the design and development of effective NDM-1 inhibitors. The discussion for each agent moves from the employed design strategy to the ability of the identified inhibitor to synergize β-lactam antibiotics. A structural analysis of NDM-1 mechanism of action based on selected X-ray complexes is also reported: the intrinsic flexibility of the binding site and the comparison between penicillin/cephalosporin and carbapenem mechanisms of hydrolysis are evaluated. Despite the valuable progress in terms of structural and mechanistic information, the design of a potent NDM-1 inhibitor to be introduced in therapy remains challenging....read more
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Journal ArticleDOI
Critical analysis of antibacterial agents in clinical development.
Ursula Theuretzbacher,Karen Bush,Stéphan Juergen Harbarth,Mical Paul,John H. Rex,Evelina Tacconelli,Guy E. Thwaites +6 more
TL;DR: There is a continued need for innovation and new-class antibacterial agents in order to provide effective therapeutic options against infections specifically caused by XDR and PDR Gram-negative bacteria.
Journal ArticleDOI
Discovery of Taniborbactam (VNRX-5133): A Broad-Spectrum Serine- And Metallo-β-lactamase Inhibitor for Carbapenem-Resistant Bacterial Infections
Bin Liu,Robert E. Lee Trout,G.-H. Chu,Mcgarry Daniel G,Randy W. Jackson,Jodie Hamrick,Denis M. Daigle,Susan M Cusick,Cecilia Pozzi,F. De Luca,M. Benvenuti,Stefano Mangani,Jean Denis Docquier,William J. Weiss,Daniel C. Pevear,Luigi Xerri,Christopher J. Burns +16 more
TL;DR: Taniborbactam is the first pan-spectrum β-lactamase inhibitor to enter clinical development and restored the activity of β- lactam antibiotics against carbapenem-resistant Pseudomonas aeruginosa and carbapanem- resistant Enterobacteriaceae.
Journal ArticleDOI
Carbapenemases: Transforming Acinetobacter baumannii into a Yet More Dangerous Menace.
TL;DR: The enzymes within the OXA, NDM, VIM, IMP, and KPC groups of carbapenemases and the coding genes found in A. baumannii clinical isolates are described.
Journal ArticleDOI
VNRX-5133 (Taniborbactam), a broad-spectrum inhibitor of serine- And metallo-β-lactamases, restores activity of cefepime in enterobacterales and Pseudomonas aeruginosa
Jodie Hamrick,Jean Denis Docquier,Tsuyoshi Uehara,Cullen L. Myers,David A. Six,Cassandra L Chatwin,Kaitlyn John,Salvador Vernacchio,Susan M Cusick,Robert E. Lee Trout,Cecilia Pozzi,Filomena De Luca,Manuela Benvenuti,Stefano Mangani,Bin Liu,Randy W. Jackson,Greg Moeck,Luigi Xerri,Christopher J. Burns,Daniel C. Pevear,Denis M. Daigle +20 more
TL;DR: Taniborbactam is a new cyclic boronate BLI that is in clinical development combined with cefepime for the treatment of infections caused by β-lactamase-producing CRE and CRPA, and is the first BLI with direct inhibitory activity against Ambler class A, B, C, and D enzymes.
Journal ArticleDOI
Fluorescent probes for the detection of disease-associated biomarkers.
Wei-Tao Dou,Hai Hao Han,Adam C. Sedgwick,Guo-Biao Zhu,Yinliang Zang,Xin Yang,Juyoung Yoon,Tony D. James,Jia Ji Li +8 more
TL;DR: Fluorescent probes have emerged as indispensable chemical tools to the field of chemical biology and medicine as discussed by the authors and have been used to detect a wide range of biologically important species in cells and in vivo.
References
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Carbapenemases: the versatile beta-lactamases.
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TL;DR: The characteristics, epidemiology, and detection of the carbapenemases found in pathogenic bacteria are updates and metallo-β-lactamases are detected primarily in Pseudomonas aeruginosa.
Journal ArticleDOI
Characterization of a New Metallo-β-Lactamase Gene, blaNDM-1, and a Novel Erythromycin Esterase Gene Carried on a Unique Genetic Structure in Klebsiella pneumoniae Sequence Type 14 from India
Dongeun Yong,Mark Toleman,Christian G. Giske,Hyun Sun Cho,Kristina Sundman,Kyungwon Lee,Timothy R. Walsh +6 more
TL;DR: A Swedish patient of Indian origin traveled to New Delhi, India, and acquired a urinary tract infection caused by a carbapenem-resistant Klebsiella pneumoniae strain that typed to the sequence type 14 complex, showing broad resistance carried on these plasmids.
Journal ArticleDOI
Updated Functional Classification of β-Lactamases
Karen Bush,George A. Jacoby +1 more
TL;DR: The functional classification scheme updated herein is based on the 1995 proposal and includes group 1 (class C) cephalosporinases; group 2 (classes A and D) broad-spectrum, inhibitor-resistant, and extended-spectrums β-lactamases and serine carbapenemases; and group 3 metallo-β-lacticamases.
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