مجال
التميز
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تميز دراسي وبحثي
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البحوث المنشورة
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البحث (1):
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عنوان البحث:
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Epidemiological and molecular
characterization of an invasive Group A Streptococcus emm32.2 outbreak
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رابط إلى البحث:
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Here
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تاريخ النشر:
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29/03/2017
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موجز عن البحث:
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An emm32.2
invasive Group A Streptococcus (iGAS) outbreak occurred in Liverpool from
January 2010 to September 2012. This genotype had not previously been
identified in Liverpool, but was responsible for 32% (14/44) of all iGAS
cases reported during this time period. We performed case-case comparison of
emm32.2 iGAS
cases with non-emm32.2 control iGAS cases identified in the Liverpool
population, over the same time period to assess patient risk factors for
emm32.2 iGAS infection. The emm32.2 iGAS cases were confined to the adult
population, we show that homelessness, intravenous drug use and alcohol abuse
predisposed
patients to emm32.2 iGAS disease, however no obvious epidemiological linkage
between the patients with emm32.2 iGAS could be identified. Comparative whole
genome sequencing analysis of emm32.2 iGAS to non-emm32.2 control isolates
was also performed to identify pathogen factors, which might have driven the
outbreak. We identified 19 genes, five
of which had previously been implicated in virulence, which were present in
all of the emm32.2 iGAS isolates but not present in any of the non40 emm32.2
control isolates. We report that a novel emm32.2 genotype emerged in
Liverpool in 2010 and
identified
a specific subset of genes , which could have allowed this novel emm32.2
genotype to persist in a disadvantaged population in the region over a
three-year period.
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المؤتمرات العلمية:
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المؤتمر (1):
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عنوان المؤتمر:
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Wellcome Trust Liverpool Glasgow Centre for
Global Health Research
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تاريخ الإنعقاد:
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30th
October – 2nd November 2016
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مكان
الإنعقاد:
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Chester,UK
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طبيعة المشاركة:
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Oral Presentation
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عنوان المشاركة:
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Characterising Group A Streptococcal
Pathogenicity
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ملخص المشاركة:
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Streptococcus
pyogenes also known as Group A Streptococcus (GAS) is among the most diverse
of any human pathogen, and has a varied range of clinical manifestations. GAS
causes mild superficial infections such as pharyngitis and serious invasive
infections such as necrotising fasciitis.
Between 2010
and 2012 there was an outbreak of invasive GAS infections in Liverpool,
Merseyside that had a mortality rate of 29%. Following sequencing, clinical
GAS isolates from the outbreak were determined as emm 32.2. The main focus of
this study was to assess the differences between the outbreak emm 32.2 strain
and other contemporaneous circulating sequence types (invasive and carriage).
This
included morphological difference analysis – capsule thickness and also the
ability of the bacteria to resist opsonophagocytosis. The next part of the
study focused on the development of in vivo models to analyse the
characteristics of pathogenicity and host immune responses during infection.
During this work, a novel septic arthritis murine model has been established
which is reproducible and an accurate representation of clinical septic
arthritis and osteomyelitis.
We
have found significant differences not only between different emm types but
also within the emm type. We have shown clear differences in how different
clinical isolates work in the murine models, and have established two unique
models to look further into the pathogenicity of GAS. Isolates that resisted
killing in vitro by macrophages, resulted in rapid septicaemia, whereas
isolates that were susceptible to killing were cleared from the mouse and in
more unique cases sequestered in the joints.
This study highlights key factors that are involved in the
pathogenesis of GAS infections and further investigates why some strains
cause fatal invasive infections and others result in mild manifestations.
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المؤتمر (2):
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عنوان المؤتمر:
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Joint BSI and NVVI Congress 2016
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تاريخ الإنعقاد:
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6-9
December 2016
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مكان
الإنعقاد:
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Liverpool, UK
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طبيعة المشاركة:
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Oral Presentation
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عنوان المشاركة:
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Phenotypic
characterisation of the Merseyside outbreak invasive Group A Streptococcus
emm32.2 strains
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ملخص المشاركة:
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Group A
Streptococcus (GAS), also known as Streptococcus pyogenes, is the cause of
important human diseases ranging from minor conditions such as pharyngitis,
to invasive infections such as necrotising fasciitis. Between 2010 to 2012,
an unusual GAS outbreak was reported in the Merseyside area which was
confined to adults, and had a propensity to occur in IV drug users, the
homeless or in alcoholics. These records showed that emm32.2 isolates were
involved in this outbreak. The mortality rate associated with the outbreak
was reported at 29%.
This project
aims to determine the phenotypic characteristics of the emm32.2 Merseyside
2010-2012 outbreak isolates to determine how differences in bacterial
attributes may be linked to differential genomic composition, and may
subsequently explain the epidemiological characteristics of this emm
subtype.
Initial
investigations consisted of comparing bacterial capsule thickness, complement
deposition and biofilm formation of invasive isolates of emm32.2 to other
invasive and non-invasive isolates from different emm types. Results
indicated that there was phenotypic heterogeneity amongst emm32.2 isolates.
Complement deposition was inversely correlated with capsule thickness;
isolates with a thick capsule were less sensitive to complement deposition.
Moreover, isolates with thicker capsule were found to be poor biofilm formers
and emm6 isolates exhibited the greatest degree of biofilm formation.
In conclusion, our results show that the
level of capsule thickness and biofilm formation are important virulence
factors responsible for invasiveness of emm32.2, other bacterial factors are
also being investigated to elucidate the full mechanism of invasiveness.
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المؤتمر (3):
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عنوان المؤتمر:
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Joint BSI and NVVI Congress 2016
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تاريخ الإنعقاد:
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6-9
December 2016
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مكان
الإنعقاد:
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Liverpool, UK
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طبيعة المشاركة:
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Oral Presentation
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عنوان المشاركة:
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Characterising the host response to Group A
Streptococcal septic arthritis
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ملخص المشاركة:
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Background
Streptococcus
pyogenes (Group A Streptococcus (GAS)) is one of most diverse human bacterial
pathogens, and has a varied range of clinical manifestations from
non-invasive infections to more serious invasive diseases including septic
arthritis. Streptococcal infection of the joints is a serious medical
emergency that is associated with significant risk of a disabling outcome.
Aims
Establish a
clinically relevant murine model of sepsis and septic arthritis to
investigate host pathogen interactions and understand the determinants of
these different clinical syndromes.
Methods
To examine
the host response to infection we set up two models; a sepsis and a novel
septic arthritis model. Immune cells were enumerated using FACs analysis from
the blood and joints over a time course. Joint histopathology analysis was
also performed. The genome sequences of the isolates were used to look for
differences that could result in different activation of the immune system.
Results
A
reproducible and clinically relevant model of sepsis and arthritis was
established. We were able to track the phases of the host response. In the
arthritis model this was characterised by an initial influx of neutrophils
and delayed migration of macrophages. Destruction of the joint followed after
the innate response corresponding with when symptoms were markedly noted in
the mice. Genomic analysis has highlighted differences in the super antigen
genes (SpeA) between the isolates that showed different pathogenicity in
vivo. GAS isolates used in the work were derived from clinical specimens.
Conclusions
We
describe a septic arthritis model using GAS, which can be used to further
investigate the mechanism of disease. Initial work suggests bacterial
characteristics may be predictive of the clinical syndrome. Research is
on-going to look further at the mechanism of immunopathogenesis within the
septic joint.
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المؤتمر (4):
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عنوان المؤتمر:
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Microbiology
Society Annual Conference 2017
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تاريخ الإنعقاد:
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3–6 April 2017
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مكان
الإنعقاد:
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Edinburgh,
UK
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طبيعة المشاركة:
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Oral
presentation
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ملخص
المشاركة:
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The Gram
positive bacterium Streptococcus pyogenes (Group A Streptococcus; GAS) is an
important human pathogen. Streptococcal infection of the joints is a serious
medical emergency that is associated with significant risk of a disabling
outcome. Streptococcus pyogenes, represents 8% of cases from England and
Wales, 9.5% in France and 16% in Australia.
We describe
a septic arthritis model using GAS, which can be used to further investigate
the mechanism of disease and we were able to track the phases of the host
response. This was characterised by an initial influx of neutrophils and
delayed migration of macrophages. Initial work suggests bacterial
characteristics may be predictive of the clinical syndrome.
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