Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp in Klebsiella pneumoniae populations

Lam, Margaret M C; Wick, Ryan R.; Wyres, Kelly L.; Gorrie, Claire L.; Judd, Louise M.; Jenney, Adam; Brisse, Sylvain; Holt, Kathryn E.

doi:10.1099/mgen.0.000196

Cited by 223 publications

(346 citation statements)

References 54 publications

(54 reference statements)

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“…We detected no evidence of the Kp virulence plasmid [21], but a minority of genomes (n=12, 12.6%) harboured the yersiniabactin siderophore locus located within three distinct chromosomally integrated ICEKp variants. The distribution of ICEKp insertions on the ST307 core genome tree indicated >4 independent acquisitions with limited expansion of recipient sublineages (Figure 2), consistent with the patterns recently reported for ST258 and other common MDR Kp clones [19]. Unlike those other clones [17,22], all ST307 shared the same capsule (KL107) and O antigen (O2v2) loci.…”

Section: St307 Virulence and Antimicrobial Resistance Genessupporting

confidence: 87%

“…We used Kleborate [19] to investigate the prevalence of acquired AMR and virulence determinants and Kaptive [20] to investigate capsule (K) and lipopolysaccharide (O) locus diversity. We detected no evidence of the Kp virulence plasmid [21], but a minority of genomes (n=12, 12.6%) harboured the yersiniabactin siderophore locus located within three distinct chromosomally integrated ICEKp variants.…”

Section: St307 Virulence and Antimicrobial Resistance Genesmentioning

confidence: 99%

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Emergence and rapid global dissemination of CTX-M-15-associated Klebsiella pneumoniae strain ST307

Wyres

Hawkey

Hetland

et al. 2018

Preprint

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Recent reports indicate the emergence of a new carbapenemase producing Klebsiella pneumoniae clone, ST307. Here we show that ST307 emerged in the mid--1990s (nearly 20 years prior to its first report), is already globally distributed and is intimately associated with a conserved plasmid harbouring the bla CTX--M--15 extended-spectrum beta--lactamase (ESBL) gene plus other antimicrobial resistance determinants. Our findings support the need for enhanced surveillance of this widespread ESBL clone in which carbapenem resistance is now emerging.

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Section: St307 Virulence and Antimicrobial Resistance Genessupporting

confidence: 87%

Section: St307 Virulence and Antimicrobial Resistance Genesmentioning

confidence: 99%

Emergence and rapid global dissemination of CTX-M-15-associated Klebsiella pneumoniae strain ST307

Wyres

Hawkey

Hetland

et al. 2018

Preprint

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“…Inspection of the most common K. pneumoniae virulence-associated mobile genetic element, ICE Kp , revealed that all strains belonging to ST11 carried an ICE Kp3 associated with a yersiniabactin operon ybt 9, while all ST258 and the ST1199 strain carried an ICE Kp2 associated with a yersiniabactin operon ybt 13, a combination usually only found in clade 1 isolates (Fig. 1) (clade 2 isolates most commonly being associated with ICE Kp10 with ybt 17) (41).…”

Section: Resultsmentioning

confidence: 99%

K. pneumoniaeST258 genomic variability and bacteriophage susceptibility

Venturini

Zakour

Bowring

et al. 2019

Preprint

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24Multidrug resistant carbapenemase-producing Klebsiella pneumoniae capable of causing 25 severe disease in humans is classified as an urgent threat by health agencies worldwide. 26 Bacteriophages are being actively explored as potential therapeutics against these multidrug 27 resistant pathogens. We are currently developing bacteriophage therapy against carbepenem-28 resistant K. pneumoniae belonging to the genetically diverse, globally disseminated clonal 29 group CG258. In an effort to define a robust experimental approach for effective selection of 30 lytic viruses for therapy, we have fully characterized the bacterial genomes of 18 target 31 strains, tested them against novel lytic bacteriophages, and generated phage-susceptibility 32 profiles. The genomes of K. pneumoniae isolates carrying blaNDM and blaKPC were sequenced 33 and isolates belonging to CG258 were selected for susceptibility testing using a panel of lytic 34 bacteriophages (n=65). The local K. pneumoniae CG258 population was dominated by 35 isolates belonging to sequence type ST258 clade 1 (86%). The primary differences between 36 ST258 genomes were variations in the capsular locus (cps) and in prophage content. We 37 showed that CG258-specific lytic phages primarily target the capsule, and that successful 38 infection is blocked in many, post-adsorption, by immunity conferred by existing prophages. 39Five bacteriophages specifically active against K. pneumoniae ST258 clade 1 (n=5) 40 belonging to the Caudovirales order were selected for further characterization. Our findings 41 show that effective control of K. pneumoniae CG258 with phage will require mixes of 42 diverse lytic viruses targeting all relevant cps variants and allowing for variable prophage 43 content. These insights will facilitate identification and selection of therapeutic phage 44 candidates against this serious pathogen. 45 46 47 48 Importance 49Bacteriophages are natural agents that exclusively and selectively kill bacteria and have the 50 potential to be useful in the treatment of multidrug resistant infections. K. pneumoniae 51 CG258 is a main agent of life-threatening sepsis that is often resistant to last-line antibiotics. 52Our work highlights some key requirements for developing bacteriophage preparations 53 targeting this pathogen. By defining the genomic profile of our clinical K. pneumoniae 54 CG258 population and matching it with bacteriophage susceptibility patterns, we found that 55 bacteriophage ability to lyse each strain correlates well with K. pneumoniae CG258 structural 56 subtypes (capsule variants). This indicates that preparation of bacteriophage therapeutics 57 targeting this pathogen should aim at including phages against each bacterial capsular 58 subtype. This necessitates a detailed understanding of the diversity of circulating isolates in 59 different geographical areas in order to make rational therapeutic choices. 60 61 62 Klebsiella pneumoniae is an important ubiquitous Gram-negative species capable of causing 63 disease in both humans an...

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“…and Citrobacter sp. 24 . Interestingly, no such genes related to secretion systems were observed in the intermediate region for Escherichia sp .…”

Section: Mainmentioning

confidence: 99%

Pangenome Analysis of Enterobacteria Reveals Richness of Secondary Metabolite Gene Clusters and their Associated Gene Sets

Mohite¹,

Lloyd²,

Monk³

et al. 2019

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13The growing number of sequenced genomes enables the study of secondary metabolite 14 biosynthetic gene clusters (BGC) in phyla beyond well-studied soil bacteria. We mined 2627 15 enterobacterial genomes to detect 8604 BGCs, including nonribosomal peptide synthetases, 16 siderophores, polyketide-nonribosomal peptide hybrids, and 60 other BGC types, with an 17 average of around 3.3 BGCs per genome. These BGCs represented 212 distinct BGC families, of 18 which only 20 have associated products in the MIBiG standard database with functions such as 19 siderophores, antibiotics, and genotoxins. Pangenome analysis identified genes associated with a 20 specific BGC encoding for colon cancer-related colibactin. In one example, we associated genes 21 involved in the type VI secretion system with the presence of a colibactin BGC in Escherichia. 22This richness of BGCs in enterobacteria opens up the possibility to discover novel secondary 23 metabolites, their physiological roles and provides a guide to identify and understand PKS 24 associated gene sets. 25 Main 26Secondary metabolites produced by a range of microorganisms display medicinally and 27 industrially important properties, as well as mediate microbe-host and microbe-microbe 28 interactions. Secondary metabolite biosynthesis often involves mega-enzymes such as polyketide 29 synthases (PKS) and non-ribosomal peptide synthetases (NRPS) that are encoded by large 30 biosynthetic gene clusters (BGCs). Recent advances in genome sequencing technology and 31 genome mining tools revealed an unexplored richness and diversity of BGCs encoding secondary 32 2 metabolites 1-4 . In addition, the availability of a large number of genomes from the same species 33 allowed for pangenome analysis revealing intra-species diversity, such as metabolic capabilities 34 5,6 . The focus of many genome mining based studies have been well-established secondary 35 metabolite producers, such as bacilli, actinobacteria, or myxobacteria 7,8 . In comparison with many 36 of the popular secondary metabolite producers, Escherichia coli or other enterobacteria have larger 37 availability of sequenced genomes, higher quality of genome annotations, comprehensive curated 38 databases, and extensive tools for data analysis. With the exception of Photorhabdus, Xenorhabdus 39 and related genera, which are known to produce a diverse range of secondary metabolites 9,10 , 40 enterobacteria are known to produce few secondary metabolites. These include metal ion chelators 41 like enterobactin, yersiniabactin 11,12 , colon cancer-related genotoxin colibactin 13,14 , antibiotic 42 althiomycin 15 , red pigment prodigiosin and biosurfactant serrawettin W1 16 . Here, we aim to 43

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Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp in Klebsiella pneumoniae populations

Cited by 223 publications

References 54 publications

Emergence and rapid global dissemination of CTX-M-15-associated Klebsiella pneumoniae strain ST307

Emergence and rapid global dissemination of CTX-M-15-associated Klebsiella pneumoniae strain ST307

K. pneumoniaeST258 genomic variability and bacteriophage susceptibility

Pangenome Analysis of Enterobacteria Reveals Richness of Secondary Metabolite Gene Clusters and their Associated Gene Sets

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