Bacterial cultures in the NCTC collection reflect the history of clinical bacterial infections stretching back over 100 years. The collection began at the end of the 19th century and additions to the collection have been made consistently ever since. Deposits come from a variety of sources including individual collections, the research community, PHE reference laboratories, and from national collections from around the world. These strains can be used as a biological resource to map microbial biodiversity and to study similarities and differences between historical and modern strains from different geographical regions.
One such study recently undertook whole genome sequencing (WGS) of over 500 Enterococcus faecium isolates, including 11 NCTC strains, to compare genomic characterisation with multilocus sequence typing (MLST). E. faecium forms part of the natural gut flora, and is also an important cause of healthcare associated infection particularly where vancomycin resistance has been acquired.
In this study three of the NCTC strains used were vancomycin resistant and eight were vancomycin sensitive; all strains had been isolated prior to 1997. Two of the resistant strains were historically important isolates from the first clinical case-report of vancomycin resistant E. faecium in the UK. Reference strains such as these can be used in research as benchmarks for mapping microbial genetic drift and gene acquisition over time.
The clinical isolates tested originated from bloodstream samples from patients the UK and Ireland between 2001 and 2011. In 17% of isolates, major discrepancies between the two methods of characterisation were found. Isolates identified as the same sequence type by MLST were shown to be genetically distinct by WGS.
Figure 1 – Concordance between MLST and WGS data
Traditionally, E. faecium has been split into to three groups; hospital-associated (Clade A1), animal-associated (Clade A2) and community-associated (Clade B). Analysis of the genomes generated in the study supported the distinction between the hospital and community-associated groups; however, there was little difference genetically between Clade A1 and A2 the hospital and animal-associated groups. WGS was therefore shown to be superior to MLST for both typing and evolutionary analysis.
Figure 2 - Population structure of E. faecium
In addition, the study showed that isolates carrying the vanA gene, which confers vancomycin resistance, were genetically indistinguishable from vancomycin sensitive isolates at the core genome level. VanA was also identified in a community-associated isolate, indicating that resistance can occur outside of the hospital-associated group. Furthermore, results indicated that there was frequent movement of E. faecium (vancomycin resistant and sensitive) between regions and countries.
The results of this study clearly indicate that the use of WGS may be of benefit in outbreak investigations to effectively monitor the spread of infection and inform infection control. The use of reference strains in research such as this assists interpretation of results by placing the microbial genomic information in temporal and geographical context.
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Raven K E, Reuter S, Reynolds R, Brodrick H J, Russell J E, Török M E, Parkhill J, Peacock S J. A decade of genomic history for healthcare-associated Enterococcus faecium in the United Kingdom and Ireland. Genome Res. 2016 Aug 15. pii: gr.204024.116. [Epub ahead of print]
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