According to our March 2008 Special Topic on MRSA
research over the past decade, the work of Professor Mark
Enright ranks at #6, with 32 papers cited a total of 1,787
times. Two of these papers are featured in the list of the
top 20 papers from the past decade.
Prof. Enright is part of the Faculty of Medicine at
Imperial College London, where he is Professor and Chair of
Molecular Epidemiology in the Division of Epidemiology,
Public Health, and Primary Care.
Prof. Enright's citation record includes 50 papers cited a total of 3,316
times between January 1, 1997 and December 31, 2007. These papers include
23 papers cited a total of 1,586 times in the field of Clinical Medicine
and 20 papers cited a total of 1,428 times in the field of
In the interview below, he talks with
ScienceWatch.com about his work with MRSA.
Please tell us a little about your research
and educational background.
My Ph.D. research at the Medical School of Aberdeen University in Scotland
was in Medical Microbiology, which, along with a Bachelor's degree in
Biological Sciences (Stirling University) and a Master's in Biochemistry
(Dundee University), gave me a good appreciation of the diseases that
bacteria can cause but also an insight into how they do it. My postdoctoral
research with Professor Brian Spratt at Sussex and Oxford Universities gave
me the chance to examine how the mechanisms by which bacteria evolve,
mutate, and exchange DNA with other strains of bacteria, impact on human
health in terms of increased resistance to antibiotics and heightened
"We know much more about the
global dissemination of particular types of MRSA than
we used to 10 years ago following the development of
MLST, and important strains can now rapidly be
identified as such and tracked to help minimize their
At this time Professor Spratt and I were beginning to trace the genetic
history of bacterial pathogens using multiple DNA sequences  and in
early work we demonstrated the power of this approach with the respiratory
pathogen Streptococcus pneumoniae This work formed the basis for
the technique called multilocus sequence
typing—MLST [2, 3]—which is now commonly used for
characterizing and tracking the spread of many human bacterial
What interested you in studying MRSA?
At the end of the last decade methicillin-resistant Staphylococcus
aureus (MRSA) had become a major problem in hospitals worldwide and
things were (and still are) particularly bad in the UK. In 1999 two
clinical colleagues in Oxford, Dr. Nick Day and Dr. Sharon Peacock
approached Professor Spratt and myself with a view to developing MLST for a
study of serious S. aureus disease in Oxford, and although I was
working on several other projects on different organisms, I figured I could
fit in one more study as it was on such a significant cause of disease.
Your most-cited original paper in our database is
the 2000 Journal of Clinical Microbiology article,
"Multilocus sequence typing for characterization of
methicillin-resistant and methicillin-susceptible clones of
Staphylococcus aureus." Would you talk a little bit about
this study and its significance to the field?
Prior to our development of an MLST scheme for S. aureus it was
difficult to compare the strains of bacteria that cause disease to those in
other hospitals, or to those that live harmlessly in the nose of
approximately a third of the human population, or to the first MRSA strains
from the 1960s. MLST uses DNA sequencing of parts of seven genes in the
bacterial chromosome and these sequences allow us to give each sample of
bacteria a "sequence type" (ST) based on these sequences that is defined as
the combination of alleles at each of the seven genes. For example ST1
S. aureus have allele 1 at all seven genes—written thus
1-1-1-1-1-1-1. ST22 isolates, the major cause of MRSA disease in the UK,
have the profile 7-6-1-5-8-8-6.
These data and information on the patient and other information on the
strain, such as antibiotic resistance profile, are stored in a database
that can be added to and interrogated at www.mlst.net. This website holds similar databases
for many bacterial pathogens of humans and animals and is a rich
resource for researchers and clinicians.
Several of your papers deal with the evolutionary
history of MRSA—would you talk about this aspect of your
S. aureus replicates by binary fission so that each bacterial cell
gives rise to two near-identical copies. Using MLST we can compare the
genetic identity of isolates separated by decades of evolution—a huge
number of generations given the fact that the generation time can be a
matter of minutes in this species. To more precisely define how the first
MRSA compare to modern strains, we used MLST and analysis of the mobile
genetic element conferring methicillin resistance in a large international
collection of MRSA and MSSA (methicillin-sensitive S. aureus). We
found that hospital MRSA evolved within only five lineages of the species,
and we pieced together the genetic events that led to the first MRSA strain
back in 1961 following the acquisition of methicillin resistance by an
epidemic MSSA strain common in the 1950s.
MRSA are now commonly found outside of hospitals in many countries. These
community-MRSA commonly cause infections in children and young adults and
they usually produce a toxin called PVL that is uncommon in hospital
strains. In work with Vandenesch and colleagues  we showed the genetic
distinction between hospital- and community-acquired lineages of MRSA, and
in a later study  showed how once successful MSSA strains carrying genes
for the PVL toxin have returned as community-acquired MRSA following a
"rearming" with resistance to many antibiotics.
How has our knowledge of MRSA advanced in the past
decade? How much more do you expect we will learn in the next 10
"Using MLST we can compare the
genetic identity of isolates separated by decades of
We know much more about the global dissemination of particular types of
MRSA than we used to 10 years ago following the development of MLST, and
important strains can now rapidly be identified as such and tracked to help
minimize their spread. However, other important advances, such as the
complete sequencing of the genomes of several MRSA strains and advances in
microarray technology, have revealed the genetic flexibility of the
organism with redundancy in many areas such as binding to host tissues,
host evasion and toxin production.
What would you like to tell the general public
about your research?
My research is geared towards understanding how organisms such as MRSA
evolve to become aggressive pathogens while developing resistance to human
interventions such as antibiotic resistance and host immunity. Only by
understanding the biology of such threats can we counter their threat to
human health with the aid of better diagnostics and
 Coffey TJ, Enright MC, Daniels M, Wilkinson P, Berron S, Fenoll A,
et al., "Serotype 19A variants of the Spanish serotype 23F
multiresistant clone of Streptococcus pneumoniae," Microb.
Drug Resist.4(1):51-5, Spring 1998.
 Enright MC, Spratt BG, "A multilocus sequence typing scheme for
Streptococcus pneumoniae: identification of clones associated with
serious invasive disease," Microbiology 144 (Pt 11): 3049-60,
 Enright MC, Robinson DA, Randle G, Feil EJ, Grundmann H, Spratt BG,
"The evolutionary history of methicillin-resistant Staphylococcus
aureus (MRSA)," Proc. Natl. Acad. Sci. USA. 99(11): 7687-92,
28 May 2002.
 Robinson DA, Kearns AM, Holmes A, Morrison D, Grundmann H, Edwards G,
et al., "Re-emergence of early pandemic Staphylococcus
aureus as a community-acquired meticillin-resistant clone,"
Lancet 365(9466): 1256-8, 2-8 April 2005.
Prof. Mark C. Enright
Division of Epidemiology, Public Health, and Primary Care
Faculty of Medicine
Imperial College London
Mark Enright's most-cited paper with 387
cites to date:
Enright MC, et al., "Multilocus sequence typing
for characterization of methicillin-resistant and
methicillin-susceptible clones of Staphylococcus aureus,"
J. Clin. Microbiol. 38(3): 1008-15, March 2000.
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