Novel VIM Metallo-β-Lactamase Variant from Clinical Isolates of Enterobacteriaceae from Algeria

The metallo-␤-lactamase VIM-4, mainly found in Pseudomonas aeruginosa or Acinetobacter baumannii, was produced in Escherichia coli and characterized by biochemical and X-ray techniques. A detailed kinetic study performed in the presence of Zn 2؉ at concentrations ranging from 0.4 to 100 M showed that VIM-4 exhibits a kinetic profile similar to the profiles of VIM-2 and VIM-1. However, VIM-4 is more active than VIM-1 against benzylpenicillin, cephalothin, nitrocefin, and imipenem and is less active than VIM-2 against ampicillin and meropenem. The crystal structure of the dizinc form of VIM-4 was solved at 1.9 Å. The sole difference between VIM-4 and VIM-1 is found at residue 228, which is Ser in VIM-1 and Arg in VIM-4. This substitution has a major impact on the VIM-4 catalytic efficiency compared to that of VIM-1. In contrast, the differences between VIM-2 and VIM-4 seem to be due to a different position of the flapping loop and two substitutions in loop 2. Study of the thermal stability and the activity of the holo-and apo-VIM-4 enzymes revealed that Zn 2؉ ions have a pronounced stabilizing effect on the enzyme and are necessary for preserving the structure.

Section: Discussionmentioning

confidence: 94%

Biochemical and Structural Characterization of the Subclass B1 Metallo-β-Lactamase VIM-4

Lassaux

Traore

Loisel

et al. 2011

“…In contrast to other countries, where the bla NDM gene has been identified mainly in Enterobacteriaceae, the bla NDM gene has been reported only in A. baumannii clinical isolates from Algeria (3, 7). However, other types of carbapenemase-acquiring isolates have been reported in Algeria, such as bla VIM in Enterobacteriaceae (8) and P. aeruginosa (9). The bla OXA-24 , bla OXA-23 , and bla OXA-58 genes have been also reported in Annaba and Tlemcen, Algeria (3, 10, 11).…”

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confidence: 99%

NDM-5 Carbapenemase-Encoding Gene in Multidrug-Resistant Clinical Isolates of Escherichia coli from Algeria

Sassi

Loucif

Gupta

et al. 2014

c Here, we report the first autochthonous cases of infections caused by bla NDM-5 New Delhi metallo-␤-lactamase-producing Escherichia coli strains recovered from urine and blood specimens of three patients from Algeria between January 2012 and February 2013. The three isolates belong to sequence type 2659 and they coexpress bla CTX-M-15 with the bla TEM-1 and bla aadA2 genes. Escherichia coli is one of the most common causative agents of infection in humans, and the emergence of resistance to thirdgeneration cephalosporins by extended-spectrum ␤-lactamases (ESBLs) has led to an increased use of carbapenem compounds (1). The growing incidence of resistance to carbapenems among Enterobacteriaceae is of major concern worldwide (1). Carbapenemase producers are mainly identified in Klebsiella pneumoniae and, to a lesser extent, in E. coli and other enterobacterial species. Carbapenemases are classified into three different classes (A, B, and D) and are now a serious problem due to their rapid spread in Enterobacteriaceae (1). Among the newly emerged ␤-lactamases in the world, New Delhi metallo-␤-lactamase (NDM) represents the latest threat for public health (2). It was first reported from K. pneumoniae and E. coli isolates recovered from a Swedish patient previously hospitalized in India (2). Since then, seven additional NDM variants have been described worldwide (2) (Fig. 1). New Delhi metallo-␤-lactamase 1 (NDM-1), which can be produced by different Enterobacteriaceae, has been reported worldwide, including recently in Acinetobacter baumannii clinical isolates in Algeria (3). In this report, we describe the first detection of bla NDM-5 -containing New Delhi metallo-␤-lactamase-producing E. coli clinical isolates in Algeria.A total of 105 consecutive and nonduplicate E. coli clinical isolates were recovered from hospitalized and nonhospitalized patients at the University Hospital of Annaba, Algeria, and were screened for carbapenem resistance between January 2012 and February 2013. During the study period, out of the 105 isolates, a total of 3 isolates harbored the bla NDM-5 gene. Out of these 3 bla NDM-5 -positive isolates, one was isolated from the blood of a 5-month-old child hospitalized in the pediatric ward, while two were isolated from urine samples from a 63-year-old man and a 75-year-old man. The isolates were identified using the Bruker Daltonics Microflex matrix-assisted laser desorption ionizationtime of flight (MALDI-TOF) mass spectrometer (Bremen, Germany), as previously described (3).These three isolates were resistant to all ␤-lactams, with an imipenem MIC of Ͼ32 g/ml and a high level of resistance to aminoglycosides and fluoroquinolones. They were susceptible only to tigecycline, fosfomycin, and colistin. Thus, NDM-5-harboring strains might be highly multidrug resistant, and a previous report on NDM-5-producing E. coli sequence type 648 (ST648) (GenBank accession no. JN104597) demonstrated that the strain was resistant to all available antimicrobials except tigecycline and colistin (4), and we obser...

“…MIC analysis showed that HSG398-V01 was more active than HSG398-DH5␣ against imipenem and ceftazidime, with 4-and 8-fold increases, respectively (Table 1), which suggested that this bla gene is functional in the three P. putida isolates. Phenotypic detection of metallo-␤-lactamases was performed on the three P. putida isolates according to the previous report (22), and synergy between imipenem and EDTA was observed for all three strains (data not shown).…”

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confidence: 99%

Presence of VIM-Positive Pseudomonas Species in Chickens and Their Surrounding Environment

Zhang

Liu

et al. 2017

Metallo-␤-lactamase gene bla VIM was identified on the chromosome of four Pseudomonas sp. isolates from a chicken farm, including one Pseudomonas aeruginosa isolate from a swallow (Yanornis martini), one Pseudomonas putida isolate from a fly, and two P. putida isolates from chickens. The four isolates shared two variants of bla VIM -carrying genomic contexts that resemble the corresponding regions of clinical metallo-␤-lactamase-producing Pseudomonas spp. Our study suggests that the surveillance of carbapenemase-producing bacteria in livestock and their surrounding environment is urgently needed.