Emergence of <italic toggle="yes">mcr-9.1</italic> in Extended-Spectrum-β-Lactamase-Producing Clinical <italic toggle="yes">Enterobacteriaceae</italic> in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome, and Mobilome

ABSTRACT Extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae are critical-priority pathogens that cause substantial fatalities. With the emergence of mobile mcr genes mediating resistance to colistin in Enterobacteriaceae, clinicians are now left with few therapeutic options. Eleven cl...

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Autores principales:	John Osei Sekyere, Nontuthuko E. Maningi, Lesedi Modipane, Nontombi Marylucy Mbelle
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	ESBLs Enterobacteriaceae mcr-9.1 South Africa critical pathogens colistin resistance Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bc30c5954be84a7b9ec03f15f70fa197
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spelling	oai:doaj.org-article:bc30c5954be84a7b9ec03f15f70fa1972021-12-02T19:47:39ZEmergence of <italic toggle="yes">mcr-9.1</italic> in Extended-Spectrum-β-Lactamase-Producing Clinical <italic toggle="yes">Enterobacteriaceae</italic> in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome, and Mobilome10.1128/mSystems.00148-202379-5077https://doaj.org/article/bc30c5954be84a7b9ec03f15f70fa1972020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00148-20https://doaj.org/toc/2379-5077ABSTRACT Extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae are critical-priority pathogens that cause substantial fatalities. With the emergence of mobile mcr genes mediating resistance to colistin in Enterobacteriaceae, clinicians are now left with few therapeutic options. Eleven clinical Enterobacteriaceae strains with resistance to cephems and/or colistin were genomically analyzed to determine their resistomes, mobilomes, and evolutionary relationships to global strains. The global phylogenomics of mcr genes and mcr-9.1-bearing genomes were further analyzed. Ten isolates were ESBL positive. The isolates were multidrug resistant and phylogenetically related to global clones but distant from local strains. Multiple resistance genes, including blaCTX-M-15 blaTEM-1, and mcr-9.1, were found in single isolates; ISEc9, IS19, and Tn3 transposons bracketed blaCTX-M-15 and blaTEM-1. Common plasmid types included IncF, IncH, and ColRNAI. mcr-9 was of close sequence identity to mcr-3, mcr-5, mcr-7, mcr-8, and mcr-10. Genomes bearing mcr-9.1 clustered into six main phyletic groups (A to F), with those of this study belonging to clade B. Enterobacter species and Salmonella species are the main hosts of mcr-9.1 globally, although diverse promiscuous plasmids disseminate mcr-9.1 across different bacterial species. Emergence of mcr-9.1 in ESBL-producing Enterobacteriaceae in South Africa is worrying, due to the restricted therapeutic options. Intensive One Health molecular surveillance might discover other mcr alleles and inform infection management and antibiotic choices. IMPORTANCE Colistin is currently the last-resort antibiotic for difficult-to-treat bacterial infections. However, colistin resistance genes that can move from bacteria to bacteria have emerged, threatening the safe treatment of many bacterial infections. One of these genes, mcr-9.1, has emerged in South Africa in bacteria that are multidrug resistant, further limiting treatment options for clinicians. In this work, we show that this new gene is disseminating worldwide through Enterobacter and Salmonella species through multiple plasmids. This worrying observation requires urgent action to prevent further escalation of this gene in South Africa and Africa.John Osei SekyereNontuthuko E. ManingiLesedi ModipaneNontombi Marylucy MbelleAmerican Society for MicrobiologyarticleESBLsEnterobacteriaceaemcr-9.1South Africacritical pathogenscolistin resistanceMicrobiologyQR1-502ENmSystems, Vol 5, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	ESBLs Enterobacteriaceae mcr-9.1 South Africa critical pathogens colistin resistance Microbiology QR1-502
spellingShingle	ESBLs Enterobacteriaceae mcr-9.1 South Africa critical pathogens colistin resistance Microbiology QR1-502 John Osei Sekyere Nontuthuko E. Maningi Lesedi Modipane Nontombi Marylucy Mbelle Emergence of <italic toggle="yes">mcr-9.1</italic> in Extended-Spectrum-β-Lactamase-Producing Clinical <italic toggle="yes">Enterobacteriaceae</italic> in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome, and Mobilome
description	ABSTRACT Extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae are critical-priority pathogens that cause substantial fatalities. With the emergence of mobile mcr genes mediating resistance to colistin in Enterobacteriaceae, clinicians are now left with few therapeutic options. Eleven clinical Enterobacteriaceae strains with resistance to cephems and/or colistin were genomically analyzed to determine their resistomes, mobilomes, and evolutionary relationships to global strains. The global phylogenomics of mcr genes and mcr-9.1-bearing genomes were further analyzed. Ten isolates were ESBL positive. The isolates were multidrug resistant and phylogenetically related to global clones but distant from local strains. Multiple resistance genes, including blaCTX-M-15 blaTEM-1, and mcr-9.1, were found in single isolates; ISEc9, IS19, and Tn3 transposons bracketed blaCTX-M-15 and blaTEM-1. Common plasmid types included IncF, IncH, and ColRNAI. mcr-9 was of close sequence identity to mcr-3, mcr-5, mcr-7, mcr-8, and mcr-10. Genomes bearing mcr-9.1 clustered into six main phyletic groups (A to F), with those of this study belonging to clade B. Enterobacter species and Salmonella species are the main hosts of mcr-9.1 globally, although diverse promiscuous plasmids disseminate mcr-9.1 across different bacterial species. Emergence of mcr-9.1 in ESBL-producing Enterobacteriaceae in South Africa is worrying, due to the restricted therapeutic options. Intensive One Health molecular surveillance might discover other mcr alleles and inform infection management and antibiotic choices. IMPORTANCE Colistin is currently the last-resort antibiotic for difficult-to-treat bacterial infections. However, colistin resistance genes that can move from bacteria to bacteria have emerged, threatening the safe treatment of many bacterial infections. One of these genes, mcr-9.1, has emerged in South Africa in bacteria that are multidrug resistant, further limiting treatment options for clinicians. In this work, we show that this new gene is disseminating worldwide through Enterobacter and Salmonella species through multiple plasmids. This worrying observation requires urgent action to prevent further escalation of this gene in South Africa and Africa.
format	article
author	John Osei Sekyere Nontuthuko E. Maningi Lesedi Modipane Nontombi Marylucy Mbelle
author_facet	John Osei Sekyere Nontuthuko E. Maningi Lesedi Modipane Nontombi Marylucy Mbelle
author_sort	John Osei Sekyere
title	Emergence of <italic toggle="yes">mcr-9.1</italic> in Extended-Spectrum-β-Lactamase-Producing Clinical <italic toggle="yes">Enterobacteriaceae</italic> in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome, and Mobilome
title_short	Emergence of <italic toggle="yes">mcr-9.1</italic> in Extended-Spectrum-β-Lactamase-Producing Clinical <italic toggle="yes">Enterobacteriaceae</italic> in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome, and Mobilome
title_full	Emergence of <italic toggle="yes">mcr-9.1</italic> in Extended-Spectrum-β-Lactamase-Producing Clinical <italic toggle="yes">Enterobacteriaceae</italic> in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome, and Mobilome
title_fullStr	Emergence of <italic toggle="yes">mcr-9.1</italic> in Extended-Spectrum-β-Lactamase-Producing Clinical <italic toggle="yes">Enterobacteriaceae</italic> in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome, and Mobilome
title_full_unstemmed	Emergence of <italic toggle="yes">mcr-9.1</italic> in Extended-Spectrum-β-Lactamase-Producing Clinical <italic toggle="yes">Enterobacteriaceae</italic> in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome, and Mobilome
title_sort	emergence of <italic toggle="yes">mcr-9.1</italic> in extended-spectrum-β-lactamase-producing clinical <italic toggle="yes">enterobacteriaceae</italic> in pretoria, south africa: global evolutionary phylogenomics, resistome, and mobilome
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/bc30c5954be84a7b9ec03f15f70fa197
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Emergence of <italic toggle="yes">mcr-9.1</italic> in Extended-Spectrum-β-Lactamase-Producing Clinical <italic toggle="yes">Enterobacteriaceae</italic> in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome, and Mobilome

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