Emergence of metallo- -lactamases GIM-1 and VIM in multidrug-resistant Pseudomonas aeruginosa in North Rhine-Westphalia, Germany

Rieber, Heime; Frontzek, André; Baum, Heike von; Pfeifer, Yvonne

doi:10.1093/jac/dkr579

Cited by 19 publications

(19 citation statements)

References 6 publications

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“…bla GIM-1 is embedded in a class 1 integron as a gene cassette and often is accompanied by various aminoglycoside resistance genes. Recent data show that bla GIM-1 has now moved into Enterobacteriaceae (11), and it has also been reported in different clones of multidrug-resistant P. aeruginosa isolates from Germany (12). The reported spread into Serratia marcescens indicates a potential transmission of mobile genetic elements carrying bla GIM-1 between different Gram-negative species.…”

mentioning

confidence: 92%

Crystal Structures of Pseudomonas aeruginosa GIM-1: Active-Site Plasticity in Metallo-β-Lactamases

Borra

Samuelsen

Spencer

et al. 2013

Antimicrob Agents Chemother

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Metallo-␤-lactamases (MBLs) have rapidly disseminated worldwide among clinically important Gram-negative bacteria and have challenged the therapeutic use of ␤-lactam antibiotics, particularly carbapenems. The bla GIM-1 gene, encoding one such enzyme, was first discovered in a Pseudomonas aeruginosa isolate from 2002 and has more recently been reported in Enterobacteriaceae. Here, we present crystal structures of GIM-1 in the apo-zinc (metal-free), mono-zinc (where Cys221 was found to be oxidized), and di-zinc forms, providing nine independently refined views of the enzyme. GIM-1 is distinguished from related MBLs in possessing a narrower active-site groove defined by aromatic side chains (Trp228 and Tyr233) at positions normally occupied by hydrophilic residues in other MBLs. Our structures reveal considerable flexibility in two loops (loop 1, residues 60 to 66; loop 2, residues 223 to 242) adjacent to the active site, with open and closed conformations defined by alternative hydrogen-bonding patterns involving Trp228. We suggest that this capacity for rearrangement permits GIM-1 to hydrolyze a wide range of ␤-lactams in spite of possessing a more constrained active site. Our results highlight the structural diversity within the MBL enzyme family.

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confidence: 92%

Crystal Structures of Pseudomonas aeruginosa GIM-1: Active-Site Plasticity in Metallo-β-Lactamases

Borra

Samuelsen

Spencer

et al. 2013

Antimicrob Agents Chemother

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“…Environmental sampling was conducted in the context of a protracted multispecies outbreak of GIM-1-producing bacteria, lasting over more than 10 years, in our hospital. This situation is unique, as GIM-1 is still locally restricted to Germany and rarely reported (10,(25)(26)(27)(28). Recently we were even able to describe a variant, GIM-2, in Düsseldorf (20).…”

Section: Discussionmentioning

confidence: 95%

“…We were also able to show the bla GIM-1 gene in a broad range of nonfermenter species typical of the aquatic environment: P. nitroreducens, P. oleovorans, A. bereziniae, A. hydrophila, and S. maltophilia. None of these species has been known to carry bla GIM-1 to date, as it has been described only in the nonfermenters P. aeruginosa, P. putida, and A. pittii (10,26,28). These bacteria have a lower clinical significance but may serve as a genetic reservoir of resistance.…”

Section: Discussionmentioning

confidence: 99%

Species Diversity of Environmental GIM-1-Producing Bacteria Collected during a Long-Term Outbreak

Wendel

Ressina

Kolbe-Busch

et al. 2016

Appl Environ Microbiol

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Reports of outbreaks concerning carbapenemase-producing Gram-negative bacteria in which the main source of transmission is the hospital environment are increasing. This study describes the results of environmental sampling in a protracted polyspecies metallo-beta-lactamase GIM-1 outbreak driven by plasmids and bacterial clones of Enterobacter cloacae and Pseudomonas aeruginosa in a tertiary care center. Environmental sampling targeting wet locations (especially sinks) was carried out on a surgical intensive care unit and on a medical ward on several occasions in 2012 and 2013. We were able to demonstrate 43 bla GIM-1 -carrying bacteria (mainly nonfermenters but also Enterobacteriaceae) that were either related or unrelated to clinical strains in 30 sinks and one hair washbasin. GIM-1 was found in 12 different species, some of which are described here as carriers of GIM-1. Forty out of 43 bacteria displayed resistance to carbapenems and, in addition, to various non-beta-lactam antibiotics. Colistin resistance was observed in two E. cloacae isolates with MICs above 256 mg/liter. The bla GIM-1 gene was harbored in 12 different class 1 integrons, some without the typical 3= end. The bla GIM-1 gene was localized on plasmids in five isolates. In vitro plasmid transfer by conjugation was successful in one isolate. The environment, with putatively multispecies biofilms, seems to be an important biological niche for multidrug-resistant bacteria and resistance genes. Biofilms may serve as a "melting pot" for horizontal gene transfer, for dissemination into new species, and as a reservoir to propagate future hospital outbreaks. IMPORTANCEIn Gram-negative bacteria, resistance to the clinically relevant broad-spectrum carbapenem antibiotics is a major public health concern. Major reservoirs for these resistant organisms are not only the gastrointestinal tracts of animals and humans but also the (hospital) environment. Due to the difficulty in eradicating biofilm formation in the latter, a sustained dissemination of multidrug-resistant bacteria from the environment can occur. In addition, horizontal transfer of resistance genes on mobile genetic elements within biofilms adds to the total "resistance gene pool" in the environment. To gain insight into the transmission pathways of a rare and locally restricted carbapenemases resistance gene (bla GIM-1 ), we analyzed the genetic background of the bla GIM-1 gene in environmental bacteria during a long-term polyspecies outbreak in a German hospital.

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“…Resistance to the β-lactam antibiotics is frequently observed in the clinical setting and is commonly due to the expression of enzymes that can hydrolyze these compounds, namely β-lactamases (645,743,(771)(772)(773). P. aeruginosa clinical isolates often harbor acquired β-lactamases particularly of the oxacillinase-(class D) and metallo-β-lactamase IMP-and VIM-types (class B) (549,608,610,614,747,748,774,775). Additionally, P. aeruginosa expresses a chromosomal cephalosporinase, AmpC, that provides intrinsic resistance and that can be expressed at high levels in the presence of β-lactams (711,712,776).…”

Section: Resultsmentioning

confidence: 99%

“…Subsequent reports identified more GIM-1-producing P. aeruginosa isolates in hospitals within a 40 km radius from the location of the original report (614). Although so far GIM-1 has not been reported outside of Germany, it has however, spread to a number of enterobacterial species including and Yersinia pestis (623), however, do not carry a chromosomal class C enzyme, although this does not preclude the possibility of carrying plasmid-borne AmpC.…”

Section: Molecular Class Bmentioning

confidence: 99%

Characterization of the poxAB Operon Encoding a Class D Carbapenemase in Pseudomonas aeruginosa,

Zincke¹

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Emergence of metallo- -lactamases GIM-1 and VIM in multidrug-resistant Pseudomonas aeruginosa in North Rhine-Westphalia, Germany

Cited by 19 publications

References 6 publications

Crystal Structures of Pseudomonas aeruginosa GIM-1: Active-Site Plasticity in Metallo-β-Lactamases

Crystal Structures of Pseudomonas aeruginosa GIM-1: Active-Site Plasticity in Metallo-β-Lactamases

Species Diversity of Environmental GIM-1-Producing Bacteria Collected during a Long-Term Outbreak

Characterization of the poxAB Operon Encoding a Class D Carbapenemase in Pseudomonas aeruginosa,

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