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Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-associated infection, but there is growing awareness of the emergence of multidrug-resistant lineages in community settings around the world. One such lineage is ST772-MRSA-V, which has disseminated globally...

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Autores principales: Steinig, Eike J, Andersson, Patiyan, Harris, Simon R, Sarovich, Derek S, Manoharan, Anand, Coupland, Paul, Holden, Matthew TG, Parkhill, Julian, Bentley, Stephen D, Robinson, D Ashley, Tong, Steven YC
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432960/
https://www.ncbi.nlm.nih.gov/pubmed/25981586
http://dx.doi.org/10.1186/s12864-015-1599-9
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author Steinig, Eike J
Andersson, Patiyan
Harris, Simon R
Sarovich, Derek S
Manoharan, Anand
Coupland, Paul
Holden, Matthew TG
Parkhill, Julian
Bentley, Stephen D
Robinson, D Ashley
Tong, Steven YC
author_facet Steinig, Eike J
Andersson, Patiyan
Harris, Simon R
Sarovich, Derek S
Manoharan, Anand
Coupland, Paul
Holden, Matthew TG
Parkhill, Julian
Bentley, Stephen D
Robinson, D Ashley
Tong, Steven YC
author_sort Steinig, Eike J
collection PubMed
description BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-associated infection, but there is growing awareness of the emergence of multidrug-resistant lineages in community settings around the world. One such lineage is ST772-MRSA-V, which has disseminated globally and is increasingly prevalent in India. Here, we present the complete genome sequence of DAR4145, a strain of the ST772-MRSA-V lineage from India, and investigate its genomic characteristics in regards to antibiotic resistance and virulence factors. RESULTS: Sequencing using single-molecule real-time technology resulted in the assembly of a single continuous chromosomal sequence, which was error-corrected, annotated and compared to nine draft genome assemblies of ST772-MRSA-V from Australia, Malaysia and India. We discovered numerous and redundant resistance genes associated with mobile genetic elements (MGEs) and known core genome mutations that explain the highly antibiotic resistant phenotype of DAR4145. Staphylococcal toxins and superantigens, including the leukotoxin Panton-Valentinin Leukocidin, were predominantly associated with genomic islands and the phage φ-IND772PVL. Some of these mobile resistance and virulence factors were variably present in other strains of the ST772-MRSA-V lineage. CONCLUSIONS: The genomic characteristics presented here emphasize the contribution of MGEs to the emergence of multidrug-resistant and highly virulent strains of community-associated MRSA. Antibiotic resistance was further augmented by chromosomal mutations and redundancy of resistance genes. The complete genome of DAR4145 provides a valuable resource for future investigations into the global dissemination and phylogeography of ST772-MRSA-V. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1599-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-44329602015-05-16 Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus Steinig, Eike J Andersson, Patiyan Harris, Simon R Sarovich, Derek S Manoharan, Anand Coupland, Paul Holden, Matthew TG Parkhill, Julian Bentley, Stephen D Robinson, D Ashley Tong, Steven YC BMC Genomics Research Article BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-associated infection, but there is growing awareness of the emergence of multidrug-resistant lineages in community settings around the world. One such lineage is ST772-MRSA-V, which has disseminated globally and is increasingly prevalent in India. Here, we present the complete genome sequence of DAR4145, a strain of the ST772-MRSA-V lineage from India, and investigate its genomic characteristics in regards to antibiotic resistance and virulence factors. RESULTS: Sequencing using single-molecule real-time technology resulted in the assembly of a single continuous chromosomal sequence, which was error-corrected, annotated and compared to nine draft genome assemblies of ST772-MRSA-V from Australia, Malaysia and India. We discovered numerous and redundant resistance genes associated with mobile genetic elements (MGEs) and known core genome mutations that explain the highly antibiotic resistant phenotype of DAR4145. Staphylococcal toxins and superantigens, including the leukotoxin Panton-Valentinin Leukocidin, were predominantly associated with genomic islands and the phage φ-IND772PVL. Some of these mobile resistance and virulence factors were variably present in other strains of the ST772-MRSA-V lineage. CONCLUSIONS: The genomic characteristics presented here emphasize the contribution of MGEs to the emergence of multidrug-resistant and highly virulent strains of community-associated MRSA. Antibiotic resistance was further augmented by chromosomal mutations and redundancy of resistance genes. The complete genome of DAR4145 provides a valuable resource for future investigations into the global dissemination and phylogeography of ST772-MRSA-V. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1599-9) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-16 /pmc/articles/PMC4432960/ /pubmed/25981586 http://dx.doi.org/10.1186/s12864-015-1599-9 Text en © Steinig et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Steinig, Eike J
Andersson, Patiyan
Harris, Simon R
Sarovich, Derek S
Manoharan, Anand
Coupland, Paul
Holden, Matthew TG
Parkhill, Julian
Bentley, Stephen D
Robinson, D Ashley
Tong, Steven YC
Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus
title Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus
title_full Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus
title_fullStr Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus
title_full_unstemmed Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus
title_short Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus
title_sort single-molecule sequencing reveals the molecular basis of multidrug-resistance in st772 methicillin-resistant staphylococcus aureus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432960/
https://www.ncbi.nlm.nih.gov/pubmed/25981586
http://dx.doi.org/10.1186/s12864-015-1599-9
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