TY  - JOUR
A1  - Siegl, Christine
A1  - Prusty, Bhupesh K.
A1  - Karunakaran, Karthika
A1  - Wischhusen, Jörg
A1  - Rudel, Thomas
T1  - Tumor Suppressor p53 Alters Host Cell Metabolism to Limit Chlamydia trachomatis Infection
JF  - Cell Reports
N2  - Obligate intracellular bacteria depend entirely on nutrients from the host cell for their reproduction. Here, we show that obligate intracellular Chlamydia downregulate the central tumor suppressor p53 in human cells. This reduction of p53 levels is mediated by the PI3K-Akt signaling pathway, activation of HDM2, and subsequent proteasomal degradation of p53. The stabilization of p53 in human cells severely impaired chlamydial development and caused the loss of infectious particle formation. DNA-damage-induced p53 interfered with chlamydial development through downregulation of the pentose phosphate pathway (PPP). Increased expression of the PPP key enzyme glucose-6-phosphate dehydrogenase rescued the inhibition of chlamydial growth induced by DNA damage or stabilized p53. Thus, downregulation of p53 is a key event in the chlamydial life cycle that reprograms the host cell to create a metabolic environment supportive of chlamydial growth.
KW  - chlamydia trachomatis
KW  - tumor
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-118200
SN  - 2211-1247
VL  - 9
IS  - 3
ER  - 
TY  - JOUR
A1  - Rudel, Thomas
A1  - Prusty, Bhupesh K.
A1  - Siegl, Christine
A1  - Hauck, Petra
A1  - Hain, Johannes
A1  - Korhonen, Suvi J.
A1  - Hiltunen-Back, Eija
A1  - Poulakkainen, Mirja
T1  - Chlamydia trachomatis Infection Induces Replication of Latent HHV-6
JF  - PLoS ONE
N2  - Human herpesvirus-6 (HHV-6) exists in latent form either as a nuclear episome or integrated into human chromosomes in more than 90% of healthy individuals without causing clinical symptoms. Immunosuppression and stress conditions can reactivate HHV-6 replication, associated with clinical complications and even death. We have previously shown that co-infection of Chlamydia trachomatis and HHV-6 promotes chlamydial persistence and increases viral uptake in an in vitro cell culture model. Here we investigated C. trachomatis-induced HHV-6 activation in cell lines and fresh blood samples from patients having Chromosomally integrated HHV-6 (CiHHV-6). We observed activation of latent HHV-6 DNA replication in CiHHV-6 cell lines and fresh blood cells without formation of viral particles. Interestingly, we detected HHV-6 DNA in blood as well as cervical swabs from C. trachomatis-infected women. Low virus titers correlated with high C. trachomatis load and vice versa, demonstrating a potentially significant interaction of these pathogens in blood cells and in the cervix of infected patients. Our data suggest a thus far underestimated interference of HHV-6 and C. trachomatis with a likely impact on the disease outcome as consequence of co-infection.
KW  - blood
KW  - chlamydia
KW  - chlamydia infection
KW  - chlamydia trachomatis
KW  - DNA replication
KW  - macrophages
KW  - polymerase chain reaction
KW  - viral load
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96731
ER  -