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Genomic characterisation of early UK MRSA isolates

ABSTRACT: Genomic characterisation of early UK MRSA isolates

PROVIDER: PRJEB2812 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	CFIK01.dat.gz	Other
	CFIK01.fasta.gz	Fasta.gz
	CFIK01.master.dat	Other
	CFNL01.dat.gz	Other
	CFNL01.fasta.gz	Fasta.gz

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Genetic Variation in Spatio-Temporal Confined USA300 Community-Associated MRSA Isolates: A Shift from Clonal Dispersion to Genetic Evolution?

Project description:Introduction Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are increasingly isolated, with USA300-0114 being the predominant clone in the USA. Comparative whole genome sequencing of USA300 isolates collected in 2002, 2003 and 2005 showed a limited number of single nucleotide polymorphisms and regions of difference. This suggests that USA300 has undergone rapid clonal expansion without great genomic diversification. However, whole genome comparison of CA-MRSA has been limited to isolates belonging to USA300. The aim of this study was to compare the genetic repertoire of different CA-MRSA clones with that of HA-MRSA from the USA and Europe through comparative genomic hybridization (CGH) to identify genetic clues that may explain the successful and rapid emergence of CA-MRSA. Materials and Methods Hierarchical clustering based on CGH of 48 MRSA isolates from the community and nosocomial infections from Europe and the USA revealed dispersed clustering of the 19 CA-MRSA isolates. This means that these 19 CA-MRSA isolates do not share a unique genetic make-up. Only the PVL genes were commonly present in all CA-MRSA isolates. However, 10 genes were variably present among 14 USA300 isolates. Most of these genes were present on mobile elements. Conclusion The genetic variation present among the 14 USA300 isolates is remarkable considering the fact that the isolates were recovered within one month and originated from a confined geographic area, suggesting continuous evolution of this clone. Data is also available from <ahref=http://bugs.sgul.ac.uk/E-BUGS-108 target=_blank>BuG@Sbase</a>

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Human DNA methylation signatures differentiate persistent from resolving MRSA bacteremia

Project description:Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is life-threatening and occurs in up to 30% of MRSA bacteremia cases despite appropriate antimicrobial therapy. Isolates of MRSA that cause antibiotic-persistent MRSA bacteremia (APMB) typically have in vitro antibiotic susceptibilities equivalent to those causing antibiotic-resolving MRSA bacteremia (ARMB). Thus, persistence reflects host-pathogen interactions occurring uniquely in context of antibiotic therapy in vivo. However, host factors and mechanisms involved in APMB remain unclear. We compared DNA methylomes in circulating immune cells from patients experiencing APMB vs. ARMB. Overall, methylation signatures diverged in the distinct patient cohorts. Differentially methylated sites intensified proximate to transcription factor binding sites, primarily in enhancer regions. In APMB patients, significant hypo-methylation was observed in binding sites for CCAAT enhancer binding protein (C/EBP) and signal transducer / activator of transcription 1 (STAT1). In contrast, hypo-methylation in ARMB patients localized to glucocorticoid receptor and histone acetyltransferase p300 binding sites. These distinct methylation signatures were enriched in neutrophils and achieved a mean area under the curve of 0.85 when used to predict APMB using a classification model. These findings differentiate epigenotypes in patients experiencing APMB vs. ARMB, and suggest a risk stratification strategy for antibiotic persistence in patients treated for MRSA bacteremia.

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