Pan European Networks - Horizon 2020 - page 42

infection and/or non-infectious trauma, inhibit
both human-infecting and porcine-infecting
chlamydial development
in vitro.
This suggests
that these molecules might play a role in
chlamydial development
in vivo,
both in
humans and in animals of agricultural and
economic importance, particularly in the context
of poly-microbial infections.
The inhibitory effect of wIRA/VIS on chlamydial
infection has been proven
in vitro
. However,
more preliminary experiments are necessary
before the wIRA device can be implemented for
the treatment of trachoma patients still
suffering from the devastating leading cause of
infectious blindness worldwide. Research in our
lab is on-going in an effort to determine the
mechanism(s) responsible for the anti-
chlamydial effect of wIRA/VIS. Our current
studies indicate that thermal as well as non-
thermal effects contribute to the inhibitory
impact of wIRA/VIS exposure on chlamydiae.
The long term goal of this project and the
described related projects is to provide further
insight into the host/pathogen interactions, pro-
inflammatory mechanisms, and immune
evasion strategies of this fascinating pathogen.
The next step will be to establish an
in vivo
sheep model to evaluate the
therapeutic effect of wIRA on conjunctivitis induced by
C. pecorum
. There
are no existing animal models for
C. trachomatis
infections with the
exception of a non-human primate model. The sheep model will be more
technically and economically feasible than a non-human primate model.
Shedding of infectious chlamydiae and subsequent inflammation will be
scored and statistically evaluated so that both the anti-chlamydial and
anti-inflammatory effects of wIRA
in vivo
can be determined.
In trachoma patients, the wIRA device could theoretically be used in
conjunction with antibiotic therapy or as an alternative to antibiotic
therapy, both to treat eye infections and to prevent disease transmission.
The wIRA device has the potential to be utilised by technical personnel
and/or physicians working to treat trachoma in a variety of settings.
Related projects
Chlamydiae not only induce trachoma but can also cause a wide range
of acute and chronic diseases in animals and humans worldwide. They
are responsible for economically important diseases such as mastitis,
endometritis, conjunctivitis and pneumonia, and those which cause
abortion in livestock. More recently, their role in asymptomatic
gastrointestinal infections with recurrent chlamydial faecal shedding has
been re-emphasised in veterinary medicine.
A recent investigation in our group demonstrated that more than 90%
of the Swiss fattening pigs harbour
C. suis
, the pig-infecting chlamydial
species, in their intestines. These chlamydiae, frequently resulting in
entirely asymptomatic infection in swine, might be considered to be a
part of the non-disease associated gut microbiome. However, on the
other hand,
C. suis
is the sole chlamydial species demonstrated capable
of acquiring stable antibiotic resistance (tetracycline resistance gene),
presumably by lateral gene transfer. The gut may therefore represent
an ideal niche and potential reservoir for dissemination of antibiotic-
resistant chlamydiae.
The ability of chlamydial organisms to establish chronic, frequently
subclinical infections has been hypothesised to correlate with chlamydial
‘persistence’ or ‘the chlamydial stress response’. Fig. 4 shows that
infectious EBs and replicative reticulate bodies (RB) comprise the
characteristic biphasic chlamydial developmental cycle. Various stressors,
including the host cytokine interferon-gamma and beta lactam antibiotics,
such as penicillin, can cause the chlamydiae to enter persistence.
Persistent chlamydiae are defined as viable but non-infectious and can
resume production of infectious EBs upon removal of the stressor.
In vitro
and
in vivo
animal studies have shown persistent chlamydiae to be
resistant to killing with azithromycin, a frontline anti-chlamydial drug.
This
in vitro
phenomenon is speculated to be associated with chronic
clinical conditions in humans such as chronic bronchitis, asthma,
atherosclerosis, reactive arthritis and genital infections in women leading
to infertility. Notably, genital serovars of
C. trachomatis
are responsible
for the most common bacterial cause of sexually transmitted diseases,
and understanding the factors affecting the pathogenicity of chlamydial
infection is therefore of broad human clinical and veterinary relevance.
Outlook
A current project in our lab investigates the mechanism leading to the
‘persistence’ chlamydial state in a co-infection model with chlamydiae
and viruses naturally occurring in the porcine gut. Additionally, we have
recently determined that damage/danger-associated molecules, typically
released from mammalian cells/tissues in the course of pathogen
I S S U E S I X
H O R I Z O N 2 0 2 0 P R O J E C T S : P O R TA L
Professor Dr Nicole Borel
Dr Cory Ann Leonard
Dr Hanna Marti
Center for Applied Biotechnology and
Molecular Medicine
University of Zürich
B R OW S E
H O R I Z O N
2 0 2 0
42
O P T O M E T R Y
Fig. 4 Chlamydial
developmental cycle,
courtesy of R V
Schoborg,
Microbes
and Infection,
2011
1...,32,33,34,35,36,37,38,39,40,41 43,44,45,46,47,48,49,50,51,52,...244
Powered by FlippingBook