Clonal emergence of Klebsiella pneumoniae ST14 co-producing OXA-48-type and NDM carbapenemases with high rate of colistin resistance in Dubai, United Arab Emirates

© 2018 Elsevier Ltd Few studies have addressed the molecular epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) isolates in the Arabian Peninsula, and such investigations have been missing from Dubai, a major economical, tourism and medical centre of the region. The antibiotic susceptibility, the carbapenemase type produced, and the clonality of 89 CRE strains isolated in five major Dubai hospitals in June 2015 to June 2016 were determined. Thirty-three percent of the collection of 70 Klebsiella pneumoniae, 13 Escherichia coli and 6 other Enterobacteriaceae were extremely drug resistant, 27% were resistant to colistin, and 4.5% (4 K. pneumoniae isolates) were resistant to all antibiotics tested. The colistin resistance rate in K. pneumoniae was 31.4%. None of the isolates carried mobile colistin resistance genes. Seventy-seven isolates produced carbapenemase: 53.3% OXA-48-like, 24.7% NDM and 22.1% both OXA-48-like and NDM, respectively. Pulsed-field gel electrophoresis clustered 50% of K. pneumoniae into a 35-membered group, which showed significant association with double carbapenemase production, with extreme drug resistance, and with being isolated from Emirati patients. Members of the cluster belonged to sequence type ST14. The rate of colistin resistance in K. pneumoniae ST14 was 37.1% vs. 27.1% of K. pneumoniae isolates outside of the cluster. Two of the panresistant K. pneumoniae isolates also belonged to ST14, whereas the other two were ST15 and ST231, respectively. In conclusion, beyond the overall high colistin resistance rate in CRE, the emergence of a highly resistant clone of K. pneumoniae ST14 in all Dubai hospitals investigated is a serious problem requiring immediate attention

Early Years of Carbapenem-Resistant <i>Enterobacterales</i> Epidemic in Abu Dhabi

Recent studies showed that the current endemic of carbapenem-resistant Enterobacterales (CRE) in the Emirate of Abu Dhabi is dominated by highly resistant Klebsiella pneumoniae clones ST14, ST231, and CC147, respectively. In the absence of continuous, molecular typing-based surveillance, it remained unknown whether they lately emerged and rapidly became dominant, or they had been present from the early years of the endemic. Therefore, antibiotic resistance, the presence of carbapenemase and 16S methylase genes, and the sequence types of CRE strains collected between 2009 and 2015 were compared with those collected between 2018 and 2019. It was found that members of these three clones, particularly those of the most prevalent ST14, started dominating already in the very early years of the CRE outbreak. Furthermore, while severely impacting the overall antibiotic resistance patterns, the effect of these clones was not exclusive: for example, increasing trends of colistin or decreasing rates of tigecycline resistance were also observed among nonclonal isolates. The gradually increasing prevalence of few major, currently dominating clones raises the possibility that timely, systematic, molecular typing-based surveillance could have provided tools to public health authorities for an early interference with the escalation of the local CRE epidemic

Molecular Characterization of MCR-1 Producing Enterobacterales Isolated in Poultry Farms in the United Arab Emirates

Data on the prevalence of MCR-producing Enterobacterales of animal origin are scarce from the Arabian Peninsula. We investigated the presence and variety of such strains from fecal specimens of poultry collected in four farms in the United Arab Emirates. Colonies from ten composite samples per farm grown on colistin-supplemented plates were PCR-screened for alleles of the mcr gene. Thirty-nine isolates selected based on species, colony morphology, and plasmid profile were subjected to whole genome sequencing. The panel of their resistance and virulence genes, MLST and cgMLST were established. Transferability and incompatibility types of the MCR-plasmids were determined. mcr-1.1 positive strains were identified in 36 of the 40 samples. Thirty-four multi-drug resistant Escherichia coli of 16 different sequence types, two Escherichia albertii, two Klebsiella pneumoniae and one Salmonella minnesota were identified. Beyond various aminoglycoside, tetracycline, and co-trimoxazole resistance genes, seven of them also carried ESBL genes and one blaCMY-2. Six IncHI2, 26 IncI2 and 4 IncX4 MCR-plasmids were mobilized, in case of the IncHI2 plasmids co-transferring ampicillin, chloramphenicol and tetracycline resistance. The diversity of mcr-1 positive strains suggest a complex local epidemiology calling for a coordinated surveillance including animals, retail meat and clinical cases

The secondary structure of the 5′ end of the FIV genome reveals a long-range interaction between R/U5 and gag sequences, and a large, stable stem–loop

Feline immunodeficiency virus (FIV) is a lentivirus that infects cats and is related to human immunodeficiency virus (HIV). Although it is a common worldwide infection, and has potential uses as a human gene therapy vector and as a nonprimate model for HIV infection, little detail is known of the viral life cycle. Previous experiments have shown that its packaging signal includes two or more regions within the first 511 nucleotides of the genomic RNA. We have undertaken a secondary structural analysis of this RNA by minimal free-energy structural prediction, biochemical mapping, and phylogenetic analysis, and show that it contains five conserved stem–loops and a conserved long-range interaction between heptanucleotide sequences 5′-CCCUGUC-3′ in R/U5 and 5′-GACAGGG-3′ in gag. This long-range interaction is similar to that seen in primate lentiviruses where it is thought to be functionally important. Along with strains that infect domestic cats, this heptanucleotide interaction can also occur in species-specific FIV strains that infect pumas, lions, and Pallas' cats where the heptanucleotide sequences involved vary. We have analyzed spliced and genomic FIV RNAs and see little structural change or sequence conservation within single-stranded regions of the 5′ UTR that are important for viral packaging, suggesting that FIV may employ a cotranslational packaging mechanism

Diversity of carbapenem-resistant Klebsiella pneumoniae ST14 and emergence of a subgroup with KL64 capsular locus in the Arabian Peninsula

To understand the reasons of successful spread of carbapenem-resistant Klebsiella pneumoniae ST14 (CRKP-ST14) in countries of the Arabian Peninsula, the resistome, capsular locus, carbapenemase carrying plasmid types, and core genome of isolates from the region were compared to global isolates. Thirty-nine CRKP-ST14 strains isolated from 13 hospitals in the United Arab Emirates, Bahrain, and Saudi Arabia were selected for whole genome sequencing on Illumina MiSeq platform based on the variety of carbapenemase genes carried and plasmids bearing these genes. Their resistome, capsular locus, and core genome MLST were compared to 173 CRKP-ST14 genomes available in public databases. The selected 39 CRKP-ST14 produced either NDM-1, OXA-48, OXA-162, OXA-232, KPC-2, or co-produced NDM-1 and an OXA-48-like carbapenemase. cgMLST revealed three clusters: 16 isolates from five UAE cities (C1), 11 isolates from three UAE cities and Bahrain (C2), and 5 isolates from Saudi Arabia (C3), respectively, and seven singletons. Resistance gene profile, carbapenemase genes, and their plasmid types were variable in both C1 and C2 clusters. The majority of CRKP-ST14 had KL2, but members of the C2 cluster and two further singletons possessed KL64 capsular locus. Based on cgMLST comparison of regional and global isolates, CRKP-ST14 with KL64 from four continents formed a distinct cluster, suggesting a recent emergence and spread of this variant. Our findings confirmed clonal transmission coupled with likely horizontal gene transfer in carbapenem-resistant Klebsiella pneumoniae ST14. Dissemination of this genetically flexible, highly resistant clone warrants further monitoring