The NDM-1 carbapenemase has been identified in 2008 in Enterobacteriaceae. Since then, several reports have emphasized its rapid dissemination throughout the world. The spread of NDM carbapenemases ...involve several bla NDM gene variants associated with various plasmids among several Gram negative species.
A multidrug-resistant E. coli isolate recovered from urine of a patient who had travelled to Burma has been characterized genetically and biochemically.
E. coli COU was resistant to all antibiotics tested except amikacin, tigecycline, fosfomycin, and chloramphenicol. Analysis of the antibiotic resistance traits identified a metallo-ß-lactamase, a novel NDM variant, NDM-7. It differs from NDM-4 by a single amino acid substitution sharing an identical extended spectrum profile towards carbapenems. The bla NDM-7 gene was located on an untypeable conjugative plasmid and associated with a close genetic background similar to those described among the bla NDM-1 genes. The isolate also harbours bla CTXM-15 and bla OXA-1 genes and belonged to ST167.
This study highlights that spread of NDM producers correspond to spread of multiple bla NDM genes and clones and therefore will be difficult to control.
Beta-Lactamase Database (BLDB) is a comprehensive, manually curated public resource providing up-to-date structural and functional information focused on this superfamily of enzymes with a great ...impact on antibiotic resistance. All the enzymes reported and characterised in the literature are presented according to the class (A, B, C and D), family and subfamily to which they belong. All three-dimensional structures of β-lactamases present in the Protein Data Bank are also shown. The characterisation of representative mutants and hydrolytic profiles (kinetics) completes the picture and altogether these four elements constitute the essential foundation for a better understanding of the structure-function relationship within this enzymes family. BLDB can be queried using different protein- and nucleotide-based BLAST searches, which represents a key feature of particular importance in the context of the surveillance of the evolution of the antibiotic resistance. BLDB is available online at
http://bldb.eu
without any registration and supports all modern browsers.
The worldwide spread of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) isolates was reported to be caused by dissemination of 1 clonal complex (i.e., clonal group CG ...258, which includes sequence types STs 258 and 512). We conducted whole-genome sequencing and epidemiologic analysis of all KPC-Kp isolates in France in 2018 and found that new successful high-risk clones of ST147, ST307, ST231, and ST383 are now the main drivers of bla
genes. The bla
genes were mostly carried by Tn4401a and Tn4401d structures and a new non-Tn4401 element. Our epidemiologic investigations showed that the emergence of these non-CG258 KPC-Kp isolates in France was linked to dissemination of these clones from Portugal. Thus, KPC-Kp epidemiology has changed in Europe, at least in several non-KPC-endemic countries of western Europe, such as France and Portugal, where CG258 is not the most prevalent clone.
The current spread of the gene encoding the metallo-ß-lactamase NDM-1 in Enterobacteriaceae is linked to a variety of surrounding genetic structures and plasmid scaffolds.
The whole sequence of ...plasmid pGUE-NDM carrying the bla(NDM-1) gene was determined by high-density pyrosequencing and a genomic comparative analysis with other bla(NDM-1)-negative IncFII was performed.
Plasmid pGUE-NDM replicating in Escherichia coli confers resistance to many antibiotic molecules including β-lactams, aminoglycosides, trimethoprim, and sulfonamides. It is 87,022 bp in-size and carries the two β-lactamase genes bla(NDM-1) and bla(OXA-1), together with three aminoglycoside resistance genes aacA4, aadA2, and aacC2. Comparative analysis of the multidrug resistance locus contained a module encompassing the bla(NDM-1) gene that is actually conserved among different structures identified in other enterobacterial isolates. This module was constituted by the bla(NDM-1) gene, a fragment of insertion sequence ISAba125 and a bleomycin resistance encoding gene.
This is the first characterized bla(NDM-1)-carrying IncFII-type plasmid. Such association between the bla(NDM-1) gene and an IncFII-type plasmid backbone is extremely worrisome considering that this plasmid type is known to spread efficiently, as examplified with the worldwide dissemination of bla(CTX-M-15)-borne IncFII plasmids.
spp. are commensal Enterobacterales of the human digestive tract. At the same time,
is commonly involved in urinary tract infections (UTI).
is naturally resistant to several antibiotics including ...colistin and shows reduced susceptibility to imipenem. However higher levels of resistance to imipenem commonly occur in
isolates consecutively to the loss of porins, reduced expression of penicillin binding proteins (PBPs) PBP1a, PBP2, or acquisition of several antibiotic resistance genes, including carbapenemase genes. In addition, resistance to non-β-lactams is also frequently reported including molecules used for treating UTI infections (e.g., fluoroquinolones, nitrofurans). Emergence and spread of multidrug resistant
isolates, including those producing ESBLs, AmpC cephalosporinases and carbapenemases, are being more and more frequently reported. This review covers
spp. with a focus on the different genetic mechanisms involved in the acquisition of resistance genes to multiple antibiotic classes turning
into a dreadful pandrug resistant bacteria and resulting in difficult to treat infections.
The immunochromatographic assay, NG-test Carba 5 (NG Biotech), has been evaluated for detection of carbapenemase-producing
(CPE) from spiked blood cultures (
= 205). It detected and discriminated in ...less than 30 minutes KPC, IMP, VIM, NDM, and OXA-48-like producers with a sensitivity and specificity of 97.7% and 96.1%, respectively. Thus, it might help the rapid optimization of treatment of bloodstream infections due to CPE.
Antibiotic resistance is rapidly spreading via the horizontal transfer of resistance genes in mobile genetic elements. While plasmids are key drivers of this process, few integrative phages encode ...antibiotic resistance genes. Here, we find that phage-plasmids, elements that are both phages and plasmids, often carry antibiotic resistance genes. We found 60 phage-plasmids with 184 antibiotic resistance genes, providing resistance for broad-spectrum-cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and colistin. These genes are in a few hot spots, seem to have been cotranslocated with transposable elements, and are often in class I integrons, which had not been previously found in phages. We tried to induce six phage-plasmids with resistance genes (including four with resistance integrons) and succeeded in five cases. Other phage-plasmids and integrative prophages were coinduced in these experiments. As a proof of concept, we focused on a P1-like element encoding an extended spectrum β-lactamase, blaCTX-M-55. After induction, we confirmed that it is capable of infecting and converting four other E. coli strains. Its reinduction led to the further conversion of a sensitive strain, confirming that it is a fully functional phage. This study shows that phage-plasmids carry a large diversity of clinically relevant antibiotic resistance genes that they can transfer across bacteria. As plasmids, these elements seem plastic and capable of acquiring genes from other plasmids. As phages, they may provide novel paths of transfer for resistance genes because they can infect bacteria that are distant in time and space from the original host. As a matter of alarm, they may also mediate transfer to other types of phages. IMPORTANCE The dissemination of antimicrobial resistance is a major threat to global health. Here, we show that a group of temperate bacterial viruses (phages), termed phage-plasmids, commonly encode different and multiple types of resistance genes of high clinical importance, often in integrons. This is unexpected, as phages typically do not carry resistance genes and, hence, do not confer upon their hosts resistance via infection and genome integration. Our experiments with phage-plasmids isolated from clinical settings confirmed that they infect sensitive strains and render them antibiotic resistant. The spread of antibiotic resistance genes by phage-plasmids is worrisome because it dispenses cell-to-cell contact, which is necessary for canonical plasmid transfer (conjugation). Furthermore, their integrons become genetic platforms for the acquisition of novel resistance genes.
With the dissemination of extremely drug resistant bacteria, colistin is now considered as the last-resort therapy for the treatment of infection caused by Gram-negative bacilli (including ...carbapenemase producers). Unfortunately, the increase use of colistin has resulted in the emergence of resistance as well. In A. baumannii, colistin resistance is mostly caused by the addition of phosphoethanolamine to the lipid A through the action of a phosphoethanolamine transferase chromosomally-encoded by the pmrC gene, which is regulated by the two-component system PmrA/PmrB. In A. baumannii clinical isolate the main resistance mechanism to colistin involves mutations in pmrA, pmrB or pmrC genes leading to the overexpression of pmrC. Although, rapid detection of resistance is one of the key issues to improve the treatment of infected patient, detection of colistin resistance in A. baumannii still relies on MIC determination through microdilution, which is time-consuming (16-24 h). Here, we evaluated the performance of a recently described MALDI-TOF-based assay, the MALDIxin test, which allows the rapid detection of colistin resistance-related modifications to lipid A (i.e phosphoethanolamine addition). This test accurately detected all colistin-resistant A. baumannii isolates in less than 15 minutes, directly on intact bacteria with a very limited sample preparation prior MALDI-TOF analysis.
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