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

Eike Steinig; Patiyan Andersson; Simon Harris; Derek Sarovich; Anand Manoharan; Paul Coupland; Matthew Holden; Julian Parkhill; Stephen Bentley; D Ashley Robinson; Steven Tong

doi:10.1186/s12864-015-1599-9

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

Eike Steinig, Patiyan Andersson, Simon Harris, Derek Sarovich, Anand Manoharan, Paul Coupland, Matthew Holden, Julian Parkhill, Stephen Bentley, D Ashley Robinson, Steven Tong

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Abstract

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 ? -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.

Original language	English
Pages (from-to)	1-10
Number of pages	10
Journal	BMC Genomics
Volume	16
Issue number	388
DOIs	https://doi.org/10.1186/s12864-015-1599-9
Publication status	Published - 16 May 2015

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Steinig, E., Andersson, P., Harris, S., Sarovich, D., Manoharan, A., Coupland, P., Holden, M., Parkhill, J., Bentley, S., Robinson, D. A., & Tong, S. (2015). Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus. BMC Genomics, 16(388), 1-10. https://doi.org/10.1186/s12864-015-1599-9

Steinig, Eike ; Andersson, Patiyan ; Harris, Simon ; Sarovich, Derek ; Manoharan, Anand ; Coupland, Paul ; Holden, Matthew ; Parkhill, Julian ; Bentley, Stephen ; Robinson, D Ashley ; Tong, Steven. / Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus. In: BMC Genomics. 2015 ; Vol. 16, No. 388. pp. 1-10.

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

abstract = "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 ? -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. ",

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author = "Eike Steinig and Patiyan Andersson and Simon Harris and Derek Sarovich and Anand Manoharan and Paul Coupland and Matthew Holden and Julian Parkhill and Stephen Bentley and Robinson, {D Ashley} and Steven Tong",

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Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus. / Steinig, Eike; Andersson, Patiyan; Harris, Simon; Sarovich, Derek; Manoharan, Anand; Coupland, Paul; Holden, Matthew; Parkhill, Julian; Bentley, Stephen; Robinson, D Ashley; Tong, Steven.

In: BMC Genomics, Vol. 16, No. 388, 16.05.2015, p. 1-10.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus

AU - Steinig, Eike

AU - Andersson, Patiyan

AU - Harris, Simon

AU - Sarovich, Derek

AU - Manoharan, Anand

AU - Coupland, Paul

AU - Holden, Matthew

AU - Parkhill, Julian

AU - Bentley, Stephen

AU - Robinson, D Ashley

AU - Tong, Steven

PY - 2015/5/16

Y1 - 2015/5/16

N2 - 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 ? -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.

AB - 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 ? -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.

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KW - bacterial strain

KW - bacterial virulence

KW - controlled study

KW - gene sequence

KW - genomic island

KW - India

KW - Malaysia

KW - methicillin resistant Staphylococcus aureus

KW - mobile genetic element

KW - molecular genetics

KW - molecular model

KW - multidrug resistance

KW - mutational analysis

KW - nonhuman

KW - nucleotide sequence

KW - Staphylococcus phage

KW - Staphylococcus aureus

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