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

BMC Genomics

Steven YC Tong³  D Ashley Robinson⁴  Stephen D Bentley¹  Julian Parkhill¹  Matthew TG Holden⁵  Paul Coupland¹  Anand Manoharan²  Derek S Sarovich³  Simon R Harris¹  Patiyan Andersson³  Eike J Steinig³ 

[1] Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK;Pushpagiri Research Center, Pushpagiri Institute of Medical Sciences and Research Center, Thiruvalla, India;Menzies School of Health Research, Darwin, Northern Territory, Australia;Department of Microbiology, University of Mississippi Medical Center, Jackson, MS, USA;School of Medicine, University of St. Andrews, St. Andrews, UK

关键词: India;    DAR4145;    Complete genome;    Mobile genetic elements;    Antibiotic resistance;    ST772;    MRSA;    Staphylococcus aureus;   

Others  :  1203935
DOI  :  10.1186/s12864-015-1599-9

 received in 2015-01-22, accepted in 2015-04-28,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Steinig et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

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