Abstract:
:In 2016, we identified a new class A carbapenemase, VCC-1, in a nontoxigenic Vibrio cholerae strain that had been isolated from retail shrimp imported into Canada for human consumption. Shortly thereafter, seven additional VCC-1-producing V. cholerae isolates were recovered along the German coastline. These isolates appear to have acquired the VCC-1 gene (blaVCC-1) independently from the Canadian isolate, suggesting that blaVCC-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 be observed in the clinic, its encroachment into aquaculture and other areas with human activity suggests that the enzyme may be emerging as a public health threat. To preemptively address this threat, we examined the structural and functional biology of VCC-1 against the FDA-approved non-β-lactam-based inhibitor avibactam. We found that avibactam restored the in vitro sensitivity of V. cholerae to meropenem, imipenem, and ertapenem. The acylation efficiency was lower for VCC-1 than for KPC-2 and akin to that of Pseudomonas aeruginosa PAO1 AmpC (k2/Ki = 3.0 × 103 M-1 s-1). 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 carbapenemase in the future.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Mangat CS,Vadlamani G,Holicek V,Chu M,Larmour VLC,Vocadlo DJ,Mulvey MR,Mark BLdoi
10.1128/AAC.02112-18subject
Has Abstractpub_date
2019-03-27 00:00:00issue
4eissn
0066-4804issn
1098-6596pii
AAC.02112-18journal_volume
63pub_type
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01364-10
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.17.4.750
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00629-08
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abstract::The antimicrobial activity of cinoxacin, 1-ethyl-4(1H)-oxo-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid, previously reported as compound 64716, was determined and compared with other antimicrobial agents at a dosage of 12 mg/kg once daily in a descending pyelonephritis rat model with Escherichia coli and Proteus mir...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.6.4.432
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02831-15
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.4.594
更新日期:1986-04-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00602-18
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abstract::The in vitro activity of TR-700 (torezolid) was evaluated against a collection of 660 staphylococcal blood isolates. TR-700 showed excellent activity against all the staphylococci tested. The MIC(50) and MIC(90) values of TR-700, linezolid, daptomycin, and vancomycin against methicillin-resistant Staphylococcus aureus...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01653-09
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.10.2716-2722.2001
更新日期:2001-10-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.6.1905-1907.2001
更新日期:2001-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02535-14
更新日期:2014-08-01 00:00:00
abstract::We investigated ertapenem-susceptible and -resistant extended-spectrum beta-lactamase-producing Enterobacter cloacae isolates obtained from the same patient. Gene transcription of OmpD and OmpF was diminished in the ertapenem-resistant isolate. An efflux pump inhibitor decreased the MICs of ertapenem in the resistant ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01591-05
更新日期:2006-08-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00429-15
更新日期:2015-01-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
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pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00172-10
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.02326-17
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abstract::The carbapenem-hydrolyzing class D β-lactamase OXA-253 was identified in an Acinetobacter baumannii clinical isolate belonging to sequence type 113 (ST113) in Brazil. OXA-253 shares 93.8% amino acid identity with OXA-143. The blaOXA-253 gene is located on a ca. 20-kb plasmid. The genetic environment of the blaOXA-253 ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02640-13
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.5.1387-1393.2001
更新日期:2001-05-01 00:00:00
abstract::Pathogenic bacterial biofilms, such as those found in the lungs of patients with cystic fibrosis (CF), exhibit increased antimicrobial resistance, due in part to the inherent architecture of the biofilm community. The protection provided by the biofilm limits antimicrobial dispersion and penetration and reduces the ef...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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abstract::Data on the effectiveness of ceftazidime-avibactam (CAZ-AVI) in critically ill, mechanically ventilated patients are limited. The present retrospective observational cohort study, which was conducted in two general intensive care units (ICUs) in central Greece, compared critically ill, mechanically ventilated patients...
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