<i>In Silico</i>
            Typing and Comparative Genomic Analysis of IncFII
            <sub>K</sub>
            Plasmids and Insights into the Evolution of Replicons, Plasmid Backbones, and Resistance Determinant Profiles

Bi, Dexi; Zheng, Jiayi; Li, Junjie; Sheng, Zhonghua; Zhu, Xingchen; Ou, Hong‐Yu; Li, Qianyu; Wei, Qing

doi:10.1128/aac.00764-18

Cited by 31 publications

(21 citation statements)

References 43 publications

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“…RND-and AcrAB-type efflux pumps that increase resistance to antimicrobial agents have been recently reported and are also involved in colistin and b-lactam resistance. 17,27,28 The strain G4 chromosome encodes seven efflux pumps, including SmeDEF, SmeMN, SmeGH, SmeP, SmeW, SmeZ, and OqxAB (Table 2). In Stenotrophomonas species phylogenetically related to strain G4, the overproduction of efflux pumps, such as SmeDEF, confers highlevel antibiotic resistance; moreover, antibiotic extrusion and colonization are both likely related to SmeDEF.…”

Section: Fig 3 Phylogenetic Relationships Ofmentioning

confidence: 99%

Co-Occurrence of Colistin and Meropenem Resistance Determinants in a Stenotrophomonas Strain Isolated from Sewage Water

Liu

et al. 2019

Microbial Drug Resistance

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Development of antibiotic resistance can be achieved either by mutation or by acquiring a resistance gene from foreign sources, with some resistance genes likely originating in microbial populations to counteract antibiotics present in natural ecosystems. In this study, we describe the first report of a strain of nonclinical multidrugresistant Stenotrophomonas sp. strain G4 with high-level resistance to colistin and meropenem, phylogenetically distinct from well-studied multiple drug-resistant species of Stenotrophomonas maltophilia. As the high-level colistin resistance of this strain was of great concern, the genome of this strain was completely sequenced. Only one chromosome was identified, and no plasmids were found. Chromosomal gene variants and other potential genetic determinants conferring resistance to colistin and meropenem were comparatively analyzed, and results showed that strain G4 harbored two putative colistin resistance determinants (named mcr-5.3 and mcr-8.2) and four extended-spectrum b-lactamase genes. In addition, 12 genes potentially encoding seven different types of efflux pumps were identified, which may have a major role in acquisition/transfer of colistin resistance. Our discovery of multiple antibiotic resistance determinants in this environmental strain extensively expands our understanding of the extent of dissemination of colistin and meropenem resistance.

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Section: Fig 3 Phylogenetic Relationships Ofmentioning

confidence: 99%

Co-Occurrence of Colistin and Meropenem Resistance Determinants in a Stenotrophomonas Strain Isolated from Sewage Water

Liu

et al. 2019

Microbial Drug Resistance

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“…The dominant plasmid identified in the present investigation belongs to the IncFII K group, found to be prevalent in K. pneumoniae but sparse in other Enterobacterales (9). The IncFIIK group of plasmids share common features, including an F-like conjugation module enabling horizontal transfer and the presence of additional replicons.…”

Section: Discussionmentioning

confidence: 68%

“…The IncFIIK group of plasmids share common features, including an F-like conjugation module enabling horizontal transfer and the presence of additional replicons. Most often, IncFII K plasmids are of narrow host range when carrying other IncF replicons (9).…”

Section: Discussionmentioning

confidence: 99%

Horizontal Plasmid Transfer among Klebsiella pneumoniae Isolates Is the Key Factor for Dissemination of Extended-Spectrum β-Lactamases among Children in Tanzania

Pedersen

Tellevik

Kommedal

et al. 2020

mSphere

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Increased knowledge about the role of horizontal gene transfer is key to improve our understanding of the spread of antimicrobial resistance (AMR) in human populations. We therefore studied the dissemination of the blaCTX-M-15 extended-spectrum-β-lactamase (ESBL) gene in Klebsiella pneumoniae isolates obtained from stool samples from hospitalized children and healthy controls below 2 years of age in Dar es Salaam, Tanzania, from August 2010 to July 2011. We performed Illumina whole-genome sequencing (WGS) to characterize resistance genes, multilocus sequence type (MLST), plasmid incompatibility group (Inc), and plasmid MLST of 128 isolates of K. pneumoniae with blaCTX-M-15 recovered from both healthy and hospitalized children. We assessed the phylogenetic relationship using single nucleotide polymorphism (SNP)-based analysis and resolved the sequences of five reference plasmids by Oxford Nanopore technology to investigate plasmid dissemination. The WGS analyses revealed the presence of a blaCTX-M-15-positive IncFIIK5/IncR plasmid with a highly conserved backbone in 70% (90/128) of the isolates. This plasmid, harboring genes encoding resistance to most β-lactams, aminoglycosides, trimethoprim-sulfamethoxazole, and chloramphenicol, was present in phylogenetically very diverse K. pneumoniae strains (48 different MLSTs) carried by both hospitalized and healthy children. Our data strongly suggest widespread horizontal transfer of this ESBL-carrying plasmid both in hospitals and in the general population. IMPORTANCE Horizontal spread of plasmids carrying multiple resistance genes is considered an important mechanism behind the global health problem caused by multidrug-resistant bacteria. Nevertheless, knowledge about spread of plasmids in a community is limited. Our detailed molecular analyses of K. pneumoniae isolated from hospitalized and healthy children in Tanzania disclosed an epidemic spread of a resistance plasmid. In this study population, we revealed horizontal plasmid transfer among K. pneumoniae as the key factor for dissemination of ESBLs. Traditional outbreak investigation and surveillance focus on the spread of bacterial clones, and short-read sequencing can result in erroneous plasmid composition. Our approach using long-read sequencing reveals horizontal gene transfer of antimicrobial resistance, and therefore has a potential impact on outbreak investigations and approaches to limit spread of AMR.

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“…In addition to their plasticity, the plasmids identified frequently harboured AMR genes other than bla KPC which might offer a selective advantage, alongside heavy metal resistance genes, and plasmid toxin-antitoxin addiction systems. The plasticity and association of IncFII K plasmids with resistance genes and IncFIB replicons has been supported by findings of a recent analysis of IncFII K plasmids(29).…”

Section: Discussionmentioning

confidence: 72%

Genomic epidemiology of a complex, multi-species plasmid-borne bla_KPC carbapenemase outbreak in Enterobacterales in the UK, 2009-2014

Stoesser

Phan

Seale

et al. 2019

Preprint

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Carbapenem resistance in Enterobacterales is a public health threat. Klebsiella pneumoniae carbapenemase (encoded by alleles of the blaKPC family) is one of the commonest transmissible carbapenem resistance mechanisms worldwide. The dissemination of blaKPC has historically been associated with distinct K. pneumoniae lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn4401). In the UK, blaKPC has caused a large-scale, persistent outbreak focused on hospitals in North-West England. This outbreak has evolved to be polyclonal and poly-species, but the genetic mechanisms underpinning this evolution have not been elucidated in detail; this study used short-read whole genome sequencing of 604 blaKPC-positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterisation. We observed the dissemination of blaKPC (predominantly blaKPC-2; 573/604 [95%] isolates) across eight species and more than 100 known sequence types. Although there was some variation at the transposon level (mostly Tn4401a, 584/604 (97%) isolates; predominantly with ATTGA-ATTGA target site duplications, 465/604 [77%] isolates), blaKPC spread appears to have been supported by highly fluid, modular exchange of larger genetic segments amongst plasmid populations dominated by IncFIB (580/604 isolates), IncFII (545/604 isolates) and IncR replicons (252/604 isolates). The subset of reconstructed plasmid sequences also highlighted modular exchange amongst non-blaKPC and blaKPC plasmids, and the common presence of multiple replicons within blaKPC plasmid structures (>60%). The substantial genomic plasticity observed has important implications for our understanding of the epidemiology of transmissible carbapenem resistance in Enterobacterales, for the implementation of adequate surveillance approaches, and for control.IMPORTANCEAntimicrobial resistance is a major threat to the management of infections, and resistance to carbapenems, one of the “last line” antibiotics available for managing drug-resistant infections, is a significant problem. This study used large-scale whole genome sequencing over a five-year period in the UK to highlight the complexity of genetic structures facilitating the spread of an important carbapenem resistance gene (blaKPC) amongst a number of bacterial species that cause disease in humans. In contrast to a recent pan-European study from 2012-2013(1), which demonstrated the major role of spread of clonal blaKPC-Klebsiella pneumoniae lineages in continental Europe, our study highlights the substantial plasticity in genetic mechanisms underpinning the dissemination of blaKPC. This genetic flux has important implications for: the surveillance of drug resistance (i.e. making surveillance more difficult); detection of outbreaks and tracking hospital transmission; generalizability of surveillance findings over time and for different regions; and for the implementation and evaluation of control interventions.

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In Silico Typing and Comparative Genomic Analysis of IncFII _K Plasmids and Insights into the Evolution of Replicons, Plasmid Backbones, and Resistance Determinant Profiles

Cited by 31 publications

References 43 publications

Co-Occurrence of Colistin and Meropenem Resistance Determinants in a Stenotrophomonas Strain Isolated from Sewage Water

Co-Occurrence of Colistin and Meropenem Resistance Determinants in a Stenotrophomonas Strain Isolated from Sewage Water

Horizontal Plasmid Transfer among Klebsiella pneumoniae Isolates Is the Key Factor for Dissemination of Extended-Spectrum β-Lactamases among Children in Tanzania

Genomic epidemiology of a complex, multi-species plasmid-borne bla_KPC carbapenemase outbreak in Enterobacterales in the UK, 2009-2014

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In Silico Typing and Comparative Genomic Analysis of IncFII K Plasmids and Insights into the Evolution of Replicons, Plasmid Backbones, and Resistance Determinant Profiles

Cited by 31 publications

References 43 publications

Co-Occurrence of Colistin and Meropenem Resistance Determinants in a Stenotrophomonas Strain Isolated from Sewage Water

Co-Occurrence of Colistin and Meropenem Resistance Determinants in a Stenotrophomonas Strain Isolated from Sewage Water

Horizontal Plasmid Transfer among Klebsiella pneumoniae Isolates Is the Key Factor for Dissemination of Extended-Spectrum β-Lactamases among Children in Tanzania

Genomic epidemiology of a complex, multi-species plasmid-borne blaKPC carbapenemase outbreak in Enterobacterales in the UK, 2009-2014

Contact Info

Product

Resources

About

In Silico Typing and Comparative Genomic Analysis of IncFII _K Plasmids and Insights into the Evolution of Replicons, Plasmid Backbones, and Resistance Determinant Profiles

Genomic epidemiology of a complex, multi-species plasmid-borne bla_KPC carbapenemase outbreak in Enterobacterales in the UK, 2009-2014