6mkq
Carbapenemase VCC-1 bound to avibactam
Structural highlights
FunctionPublication Abstract from PubMedIn 2016 we identified a new class A carbapenemase, VCC-1, in nontoxigenic Vibrio cholerae that had been isolated from retail shrimp imported into Canada for human consumption. Shortly thereafter, seven additional VCC-1 producing V. cholerae were isolated along the German coastline. These isolates appear to have acquired the VCC-1 gene (bla VCC-1) independently from the Canadian isolate, suggesting bla VCC-1 is mobile and widely distributed. VCC-1 hydrolyzes penicillins, cephalothin, aztreonam, and carbapenems, and like the broadly disseminated class A carbapenemase KPC-2, is only weakly inhibited by clavulanic acid or tazobactam. Although VCC-1 has yet to observed in the clinic, its encroachment into aquaculture and other areas with human activity suggests the enzyme may be emerging as a public health threat. To pre-emptively address this threat, we examined the structural and functional biology of VCC-1 against the FDA approved non-beta-lactam-based inhibitor avibactam. We found that avibactam restored the in vitro sensitivity of V. cholerae to meropenem, impenem and ertapenem. Acylation efficiency was lower for VCC-1 as compared to KPC-2 and akin to that of Pseudomonas aeruginosa PAO1 AmpC (k2/Ki=3.0 x 10(3) M(-1)sec(-137)). The tertiary structure of VCC-1 is similar to that of KPC-2 and they bind avibactam similarly; however, our analyses suggest that VCC-1 may be unable to degrade avibactam as has been found for KPC-2. Based on our prior genomics-based surveillance, we were able to target VCC-1 for detailed molecular studies to gain early insights that could be used to combat this carbapenemse in the future. Molecular basis for the potent inhibition of the emerging carbapenemase VCC-1 by avibactam.,Mangat CS, Vadlamani G, Holicek V, Chu M, Larmour V, Vocadlo DJ, Mulvey MR, Mark BL Antimicrob Agents Chemother. 2019 Feb 19. pii: AAC.02112-18. doi:, 10.1128/AAC.02112-18. PMID:30782990[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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