Emergence of an Extensively Drug-Resistant <italic toggle="yes">Salmonella enterica</italic> Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins

ABSTRACT 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...

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Autores principales:	Elizabeth J. Klemm, Sadia Shakoor, Andrew J. Page, Farah Naz Qamar, Kim Judge, Dania K. Saeed, Vanessa K. Wong, Timothy J. Dallman, Satheesh Nair, Stephen Baker, Ghazala Shaheen, Shahida Qureshi, Mohammad Tahir Yousafzai, Muhammad Khalid Saleem, Zahra Hasan, Gordon Dougan, Rumina Hasan
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	antibiotic resistance Salmonella Typhi typhoid Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/83d1da76553346da82eb5ef1f2ae6c0b
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spelling	oai:doaj.org-article:83d1da76553346da82eb5ef1f2ae6c0b2021-11-15T15:53:26ZEmergence of an Extensively Drug-Resistant <italic toggle="yes">Salmonella enterica</italic> Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins10.1128/mBio.00105-182150-7511https://doaj.org/article/83d1da76553346da82eb5ef1f2ae6c0b2018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00105-18https://doaj.org/toc/2150-7511ABSTRACT 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.Elizabeth J. KlemmSadia ShakoorAndrew J. PageFarah Naz QamarKim JudgeDania K. SaeedVanessa K. WongTimothy J. DallmanSatheesh NairStephen BakerGhazala ShaheenShahida QureshiMohammad Tahir YousafzaiMuhammad Khalid SaleemZahra HasanGordon DouganRumina HasanAmerican Society for Microbiologyarticleantibiotic resistanceSalmonellaTyphityphoidMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibiotic resistance Salmonella Typhi typhoid Microbiology QR1-502
spellingShingle	antibiotic resistance Salmonella Typhi typhoid Microbiology QR1-502 Elizabeth J. Klemm Sadia Shakoor Andrew J. Page Farah Naz Qamar Kim Judge Dania K. Saeed Vanessa K. Wong Timothy J. Dallman Satheesh Nair Stephen Baker Ghazala Shaheen Shahida Qureshi Mohammad Tahir Yousafzai Muhammad Khalid Saleem Zahra Hasan Gordon Dougan Rumina Hasan Emergence of an Extensively Drug-Resistant <italic toggle="yes">Salmonella enterica</italic> Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins
description	ABSTRACT 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.
format	article
author	Elizabeth J. Klemm Sadia Shakoor Andrew J. Page Farah Naz Qamar Kim Judge Dania K. Saeed Vanessa K. Wong Timothy J. Dallman Satheesh Nair Stephen Baker Ghazala Shaheen Shahida Qureshi Mohammad Tahir Yousafzai Muhammad Khalid Saleem Zahra Hasan Gordon Dougan Rumina Hasan
author_facet	Elizabeth J. Klemm Sadia Shakoor Andrew J. Page Farah Naz Qamar Kim Judge Dania K. Saeed Vanessa K. Wong Timothy J. Dallman Satheesh Nair Stephen Baker Ghazala Shaheen Shahida Qureshi Mohammad Tahir Yousafzai Muhammad Khalid Saleem Zahra Hasan Gordon Dougan Rumina Hasan
author_sort	Elizabeth J. Klemm
title	Emergence of an Extensively Drug-Resistant <italic toggle="yes">Salmonella enterica</italic> Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins
title_short	Emergence of an Extensively Drug-Resistant <italic toggle="yes">Salmonella enterica</italic> Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins
title_full	Emergence of an Extensively Drug-Resistant <italic toggle="yes">Salmonella enterica</italic> Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins
title_fullStr	Emergence of an Extensively Drug-Resistant <italic toggle="yes">Salmonella enterica</italic> Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins
title_full_unstemmed	Emergence of an Extensively Drug-Resistant <italic toggle="yes">Salmonella enterica</italic> Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins
title_sort	emergence of an extensively drug-resistant <italic toggle="yes">salmonella enterica</italic> serovar typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third-generation cephalosporins
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/83d1da76553346da82eb5ef1f2ae6c0b
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Emergence of an Extensively Drug-Resistant <italic toggle="yes">Salmonella enterica</italic> Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins

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