Genomic Characteristics of NDM-Producing Enterobacteriaceae Isolates in Australia and Their
            <i>bla</i>
            <sub>NDM</sub>
            Genetic Contexts

Wailan, Alexander M.; Paterson, David L.; Kennedy, Karina; Ingram, Paul R.; Bursle, Evan; Sidjabat, Hanna E.

doi:10.1128/aac.01243-15

Cited by 73 publications

(64 citation statements)

References 42 publications

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“…However, we were unable to establish such a link. pKpN01-NDM7 is an IncX3 plasmid; IncX3 plasmids are usually self-transferable and have been associated with the spread of several antimicrobial-resistant genes, including carbapenemase genes, such as bla NDM (33)(34)(35)(36)(37), bla KPC (38), and bla OXA-181 (39,40). A BLAST search against the GenBank sequence database revealed that pKpN01-NDM7 is highly similar to other bla NDMharboring IncX3 plasmids, including pNDM-HN380 (bla NDM-1 ) (36), p112298-NDM (bla NDM-1 ; GenBank accession number KP987216), pEc1929 (bla NDM-5 ; GenBank accession number KT824791), pNDM_MGR194 (bla NDM-5 ) (34), pJEG027 (bla NDM-4 ) (35), and pOM26-1 (bla NDM-7 ; GenBank accession number KP776609) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Molecular Characterization by Using Next-Generation Sequencing of Plasmids Containing bla _NDM-7 in Enterobacteriaceae from Calgary, Canada

Chen

Peirano

Lynch

et al. 2016

Antimicrob Agents Chemother

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g Enterobacteriaceae with bla NDM-7 are relatively uncommon and had previously been described in Europe, India, the United States, and Japan. This study describes the characteristics of Enterobacteriaceae (Klebsiella pneumoniae Epidemiological and molecular studies are required to better understand the dynamics of transmission, the risk factors, and the reservoirs for bacteria harboring bla NDM-7 . To the best of our knowledge, this is the first report of S. marcescens and E. hormaechei with bla NDM-7 .

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Section: Resultsmentioning

confidence: 99%

Molecular Characterization by Using Next-Generation Sequencing of Plasmids Containing bla _NDM-7 in Enterobacteriaceae from Calgary, Canada

Chen

Peirano

Lynch

et al. 2016

Antimicrob Agents Chemother

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“…The NDM-5-encoding gene bla was first identified in an Escherichia coli strain recovered from a patient in the United Kingdom in 2011 (3). Since then, bla was identified in many countries, such as Algeria (4)(5)(6), the United States (7), Australia (8), China (9)(10)(11)(12), Denmark (13), Japan (14), India (15), and the United Kingdom (3). The widespread occurrence of NDM-5 in recent years should arouse our attention.…”

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confidence: 99%

Various Sequence Types of Escherichia coli Isolates Coharboring bla _NDM-5 and mcr-1 Genes from a Commercial Swine Farm in China

Kong

Lei

et al. 2017

Antimicrob Agents Chemother

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Sixteen different sequence types (STs) of Escherichia coli isolates from a commercial swine farm in China were confirmed to coharbor the carbapenem resistance gene bla and the colistin resistance gene mcr-1. Whole-genome sequencing revealed that bla NDM-5 and mcr-1 were located on a 46-kb IncX3 plasmid and a 32-kb IncX4 plasmid, respectively. The two plasmids can transfer together with a low fitness cost, which might explain the presence of various STs of E. coli coharboring bla NDM-5 and mcr-1.KEYWORDS Escherichia coli, carbapenems, bla NDM-5 , colistin, mcr-1, fitness cost C arbapenemase-producing Enterobacteriaceae has become a major public health threat around the world (1). The recently identified carbapenemase New Delhi metallo-␤-lactamase confers resistance to all ␤-lactam antimicrobials except monobactam (2). The NDM-5-encoding gene bla NDM-5 was first identified in an Escherichia coli strain recovered from a patient in the United Kingdom in 2011 (3). Since then, bla was identified in many countries, such as Algeria (4-6), the United States (7), Australia (8), China (9-12), Denmark (13), Japan (14), India (15), and the United Kingdom (3). The widespread occurrence of NDM-5 in recent years should arouse our attention. Colistin is a critically important medication for humans in the treatment of carbapenemaseproducing Enterobacteriaceae, and it has been widely used in veterinary medicine in China (16,17). The first plasmid-mediated colistin resistance gene, mcr-1, was reported in E. coli in 2015 (18). In a short period, colistin-resistant E. coli carrying the mcr-1 gene were reported worldwide (19,20). Recently, mcr-1 was reported to coexist with bla NDM (21-23) and bla CTX-M (24), which brought great challenges for the treatment of bacterial infection. In the present study, we are the first to report the presence of isolates of various sequence types of E. coli coharboring bla NDM-5 and mcr-1 genes from a commercial pig farm in China.A total of 105 anal swabs samples from swine were collected from a commercial pig farm on 1 October 2015 in Sichuan province. E. coli strains were selected by eosinmethylene blue agar, and only 1 isolate was picked up from each sample. All 105 isolates were identified by BD Phoenix 100 diagnostic systems (Sparks, MD). Sixty-four strains were nonsusceptible to imipenem and polymyxin B, identified by the agar dilution method according to Clinical and Laboratory Standards Institute guidelines (25). Isolates were divided into 16 different clones by pulsed-field gel electrophoresis after XbaI digestion according to the standard PulseNet conditions (26) (Fig. 1). Phy-

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“…Limited studies have described the plasmid features and genetic contexts of NDM-producers from Australia (22,75,227).…”

Section: Acknowledgmentsmentioning

confidence: 99%

“…Treatment options for these infections are diminishing with isolates frequently reported as resistant to major last-line antimicrobials, such as carbapenems and colistin (22,23). The genes conferring resistance to major classes of antimicrobials are often carried on extrachromosomal DNA elements, known as plasmids, which can act to disseminate these genes amongst the broader bacterial population (2,39,40,198).…”

Section: Introductionmentioning

confidence: 99%

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The genetic analysis of Enterobacteriaceae plasmids to provide insights into the acquisition and spread of the blaNDM gene

Wailan¹

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Treatment options for infections caused by pathogenic Gram-negative bacteria, especially those of the Enterobacteriaceae family, are becoming limited with the increase of antimicrobial resistance (AMR). β-lactamases are a major mechanism for AMR within the Enterobacteriaeae. The most problematic β-lactamases are carbapenemases, which confer resistance to carbapenems, the major last-line antimicrobial. A recently emerged carbapenemase that has globally disseminated is the NDM carbapenemase, provided by blaNDM genes. These blaNDM genes (and other AMR genes) are able to transmit between strains when inserted on extrachromosomal self-replicating DNA molecules known as 'plasmids'. AMR genes within Enterobacteriacae are frequently associated with specific bacterial species, clonal lineage, plasmid Incompatibility (Inc) types or transposable elements. The blaNDM genes however do not have this association when oberserved in the Enterobacteriaceae family. To address and characterise this new paradigm presented by blaNDM genes, this thesis presents the bioinformatic analysis of plasmids associated with the Enterobacteriaceae to provide insights into the acquisition and spread of the blaNDM gene and an epidemiological approach to assess its plasmid-mediated dissemination between genetically unrelated species.Specifically these aims were achieved by; firstly, the establishment of a recent account of the blaNDM gene from an epidemiological perspective using a novel genetic/molecular approach. This would identify the spread of individual plasmids carrying blaNDM across multiple species and patients, both within a single facility and across multiple national facilities. The approach combined in-depth bioinformatic analysis of blaNDM genetic contexts (NGCs) with common molecular epidemiology techniques. IncN2 (n=4) and IncA/C (n=3) were identified as the most common plasmids types carrying blaNDM across four patients within a Pakistani military hospital. These patients harboured between two and four NDM-1 producing Gram-negative bacilli of different ii species coresident in their stool samples. IncFII-types (n=7) and IncX3 (n=4) were the most common plasmid types carrying blaNDM amongst 12 Enterobacteriaceae isolates, each from different patients across multiple Australian healthcare facilities. These isolates each carried one plasmid harbouring blaNDM but only five different blaNDM genetic contexts were identified, indicating five particular plasmids with a specific NGC had disseminated amongst these 12 isolates.Secondly, to investigate transposable elements involved for insertion of the blaNDM gene into different plasmid types, the complete sequence of four plasmids carrying blaNDM (two IncA/C2 and two IncFIIY) was bioinformatically analysed. These plasmids were from four different clinical samples of four patients, comprised of Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli. Each plasmid was observed to acquire blaNDM by different mechanisms on very similar plasmid backbones. Transposable elements ...

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Genomic Characteristics of NDM-Producing Enterobacteriaceae Isolates in Australia and Their bla _NDM Genetic Contexts

Cited by 73 publications

References 42 publications

Molecular Characterization by Using Next-Generation Sequencing of Plasmids Containing bla _NDM-7 in Enterobacteriaceae from Calgary, Canada

Molecular Characterization by Using Next-Generation Sequencing of Plasmids Containing bla _NDM-7 in Enterobacteriaceae from Calgary, Canada

Various Sequence Types of Escherichia coli Isolates Coharboring bla _NDM-5 and mcr-1 Genes from a Commercial Swine Farm in China

The genetic analysis of Enterobacteriaceae plasmids to provide insights into the acquisition and spread of the blaNDM gene

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Genomic Characteristics of NDM-Producing Enterobacteriaceae Isolates in Australia and Their bla NDM Genetic Contexts

Cited by 73 publications

References 42 publications

Molecular Characterization by Using Next-Generation Sequencing of Plasmids Containing bla NDM-7 in Enterobacteriaceae from Calgary, Canada

Molecular Characterization by Using Next-Generation Sequencing of Plasmids Containing bla NDM-7 in Enterobacteriaceae from Calgary, Canada

Various Sequence Types of Escherichia coli Isolates Coharboring bla NDM-5 and mcr-1 Genes from a Commercial Swine Farm in China

The genetic analysis of Enterobacteriaceae plasmids to provide insights into the acquisition and spread of the blaNDM gene

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Product

Resources

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Genomic Characteristics of NDM-Producing Enterobacteriaceae Isolates in Australia and Their bla _NDM Genetic Contexts

Molecular Characterization by Using Next-Generation Sequencing of Plasmids Containing bla _NDM-7 in Enterobacteriaceae from Calgary, Canada

Molecular Characterization by Using Next-Generation Sequencing of Plasmids Containing bla _NDM-7 in Enterobacteriaceae from Calgary, Canada

Various Sequence Types of Escherichia coli Isolates Coharboring bla _NDM-5 and mcr-1 Genes from a Commercial Swine Farm in China