Revolutionary strategy for control and prevention of hospital
1 February 2010
For the first time, researchers have shown how transmission of
MRSA from one person to another can be precisely tracked in a hospital
A research team from the Wellcome Trust Sanger Institute, Bath
University Cambridge University and Mahidol University, Bangkok have
developed a remarkable new method that can ‘zoom’ from large-scale
inter-continental transmission events to the much finer detail of
person-to-person infection of MRSA within a single hospital .
The ability to track strains in this way will enable researchers to
understand how strains can spread so rapidly, and should lead to novel
infection control strategies, not only for MRSA but also for other
The team used new very high-throughput DNA sequencing technologies to
compare individual MRSA isolates from patients to precisely show their
genetic relatedness. Very quickly they were able to spot single-letter
changes in the genetic code and to identify differences between even the
most closely related of MRSA isolates.
“We looked at two very different sets of samples,” explains Dr Simon
Harris, from the Wellcome Trust Sanger Institute and co-lead author on
the study. “We have 42 samples taken from people across the globe, who
became infected with MRSA between 1982 and 2003. The second set is from
a single hospital in northeast Thailand, and consists of 20 samples from
patients who developed MRSA infection within 7 months of each other, all
possibly linked by a chain of person-to-person transmission”
“We wanted to test whether our method could successfully zoom in and
out to allow us to track infection on a global scale – from
continent-to-continent, and also on the smallest scale – from
The team sequenced the whole genomes of all the samples using a
next-generation DNA sequencing technology. This technique reveals the
minutiae of single-letter genetic changes in the hospital samples, and
showed that no two infections were caused by entirely identical
Based on these subtle genetic differences, the researchers divided
the Thai hospital samples into two groups. In the larger group of 13
bacteria they found five which were extremely similar and differed
altogether by just 14 single-letter changes.
“This group of five related MRSA strains caused infections in
patients who were resident in intensive care units in adjacent blocks of
the hospital,” explains Dr Ed Feil, from the Department of Biology and
Biochemistry at the University of Bath and co-lead author on the study,
“and all were isolated within a few weeks of each other. By contrast,
bacteria from patients housed in other parts of the hospital were much
“This cemented our theory — based on the sequence comparison — that
there were two different groups of isolates that had had been introduced
to the hospital separately.”
Importantly, the team was also able to determine the rate at which
DNA sequence typically mutated, providing an unprecedented insight into
the rate of evolution in vivo. The particular MRSA strain studied
acquired about one single-letter change every six weeks.
To understand better the evolution and global spread of MRSA over
several decades and large geographic distances, the team looked at
samples from hospitals in North and South America, Europe, Australia and
Asia collected over a period of more than twenty years by the CEM/NET
Initiative, an international project in molecular epidemiology organized
by Instituto de Tecnologia Química e Biológica (ITQB) and The
Rockefeller University — and headed by Dr Herminia de Lencastre.
By identifying single letter changes in the individual genomes and
making calculations based on the dates at which the samples were taken,
the team derived a mutation rate and developed an evolutionary tree of
MRSA. One major interest from these studies is to suggest where and when
this type of MRSA might have emerged.
The European isolates were concentrated around the base of the
evolutionary tree and their calculated mutation rate suggested that this
MRSA emerged in the 1960s in Europe, bolstering established theories
that the origins of MRSA correlate with the introduction of widespread
antibiotic use in Europe in the 1960s.
The team also found that clusters of isolates that were genetically
very similar were typically also highly consistent in their geographic
“Telling the difference between isolates within one species is
fundamentally important in the development of public health strategies,”
says Dr Stephen Bentley, from the Wellcome Trust Sanger Institute and
senior author on the study. “It allows researchers and public health
officials to see how infections are spread: from person to person; from
hospital to hospital; from country to country.”
For many years, scientists have been searching for improved methods
to allow them to distinguish, reliably and within the same species, one
bacterial isolate from another. Until now, even the best methods for
identifying the differences between bacterial genomes have been unable
to differentiate between all isolates — leaving gaps and uncertainties
in pathways of transmission.
The success of the new method relies on comparing whole genomes,
whereas previous methods have relied on looking at either single loci or
limited numbers of regions in the genome.
“This new method has allowed us to gain insights into fundamental
processes of evolution in S. aureus, one of the most important
bacterial pathogens in healthcare in the world,” explains Dr Sharon
Peacock, from the Department of Medicine at the University of Cambridge
University and the Faculty of Tropical Medicine at Mahidol University,
Bangkok, Thailand and an author on the study. “We are now able to
discriminate between one strain and another, even where they are very
closely related. Our research should inform global surveillance
strategies to track the spread of MRSA.
“The implications for public health are clear: this technology
represents the potential to trace transmission pathways of MRSA more
definitively so that interventions or treatments can be targeted with
precision and according to need."
It is not only applicable to MRSA: the research reaches further into
public health. The team suggest that the new approach could underpin
future studies into the transmission and evolution of other bacteria
that are a significant health burden.
1. Harris S, Feil EJ et al. (2010) Evolution of MRSA during
hospital transmission and intercontinental spread. Science.
Available online at doi: 10.1126/science.1182395