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Attributes of carbapenemase encoding conjugative plasmid pNDM-SAL from an extensively drug-resistant Salmonella enterica Serovar Senftenberg.

ABSTRACT: A carbapenem resistant Salmonella enterica serovar Senftenberg isolate BCH 2406 was isolated from a diarrheal child attending an outpatient unit of B.C. Roy Hospital in Kolkata, India. This isolate was positive for the bla NDM-1 in the PCR assay, which was confirmed by amplicon sequencing. Except for tetracycline, this isolate was resistant to all the tested antimicrobials. The bla NDM-1 was found to be located on a 146.13-kb mega plasmid pNDM-SAL, which could be conjugally transferred into Escherichia coli and other enteric pathogens such as Vibrio cholerae O1 Ogawa and Shigella flexneri 2a. However, the expression of ?-lactam resistance is not the same in different bacteria. The whole genome sequence of pNDM-SAL was determined and compared with other pNDM plasmids available in public domain. This plasmid is an IncA/C incompatibility type composed of 155 predicted coding sequences and shares homology with plasmids of E. coli pNDM-1_Dok01, Klebsiella pNDM-KN, and Citrobacter pNDM-CIT. In pNDM-SAL, gene cluster containing bla NDM-1 was located between IS26 and IS4321 elements. Between the IS26 element and the bla NDM-1, a truncated ISAba125 insertion sequence was identified. Downstream of the bla NDM-1, other genes, such as ble MBL, trpF, tat, and an ISCR1 element with class 1 integron containing aac(6')-Ib were detected. Another ?-lactacamase gene, bla CMY -4 was found to be inserted in IS1 element within the type IV conjugative transfer loci of the plasmid. This gene cluster had blc and sugE downstream of the bla CMY -4. From our findings, it appears that the strain S. Senftenberg could have acquired the NDM plasmid from the other members of Enterobacteriaceae. Transfer of NDM plasmids poses a danger in the management of infectious diseases.

SUBMITTER: Sarkar A

PROVIDER: S-EPMC4569734 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Attributes of carbapenemase encoding conjugative plasmid pNDM-SAL from an extensively drug-resistant Salmonella enterica Serovar Senftenberg.

Sarkar Anirban A Pazhani Gururaja P GP Chowdhury Goutam G Ghosh Amit A Ramamurthy Thandavarayan T

Frontiers in microbiology 20150915

A carbapenem resistant Salmonella enterica serovar Senftenberg isolate BCH 2406 was isolated from a diarrheal child attending an outpatient unit of B.C. Roy Hospital in Kolkata, India. This isolate was positive for the bla NDM-1 in the PCR assay, which was confirmed by amplicon sequencing. Except for tetracycline, this isolate was resistant to all the tested antimicrobials. The bla NDM-1 was found to be located on a 146.13-kb mega plasmid pNDM-SAL, which could be conjugally transferred into Esch ...[more]

PMID: 26441902

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Project description:Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel S Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant (XDR). Over 300 XDR typhoid cases have emerged in Sindh, Pakistan, since November 2016. Additionally, a single case of travel-associated XDR typhoid has recently been identified in the United Kingdom. Whole-genome sequencing of over 80 of the XDR isolates revealed remarkable genetic clonality and sequence conservation, identified a large number of resistance determinants, and showed that these isolates were of haplotype H58. The XDR S Typhi clone encodes a chromosomally located resistance region and harbors a plasmid encoding additional resistance elements, including the blaCTX-M-15 extended-spectrum β-lactamase, and carrying the qnrS fluoroquinolone resistance gene. This antibiotic resistance-associated IncY plasmid exhibited high sequence identity to plasmids found in other enteric bacteria isolated from widely distributed geographic locations. This study highlights three concerning problems: the receding antibiotic arsenal for typhoid treatment, the ability of S Typhi to transform from MDR to XDR in a single step by acquisition of a plasmid, and the ability of XDR clones to spread globally.IMPORTANCE Typhoid fever is a severe disease caused by the Gram-negative bacterium Salmonella enterica serovar Typhi. Antibiotic-resistant S Typhi strains have become increasingly common. Here, we report the first large-scale emergence and spread of a novel extensively drug-resistant (XDR) S Typhi clone in Sindh, Pakistan. The XDR S Typhi is resistant to the majority of drugs available for the treatment of typhoid fever. This study highlights the evolving threat of antibiotic resistance in S Typhi and the value of antibiotic susceptibility testing and whole-genome sequencing in understanding emerging infectious diseases. We genetically characterized the XDR S Typhi to investigate the phylogenetic relationship between these isolates and a global collection of S Typhi isolates and to identify multiple genes linked to antibiotic resistance. This S Typhi clone harbored a promiscuous antibiotic resistance plasmid previously identified in other enteric bacteria. The increasing antibiotic resistance in S Typhi observed here adds urgency to the need for typhoid prevention measures.

Dataset Information

Attributes of carbapenemase encoding conjugative plasmid pNDM-SAL from an extensively drug-resistant Salmonella enterica Serovar Senftenberg.

Publications

Attributes of carbapenemase encoding conjugative plasmid pNDM-SAL from an extensively drug-resistant Salmonella enterica Serovar Senftenberg.

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