TY  - JOUR
A1  - Handtke, Stefan
A1  - Schroeter, Rebecca
A1  - Jürgen, Britta
A1  - Methling, Karen
A1  - Schlüter, Rabea
A1  - Albrecht, Dirk
A1  - Hijum, Sacha A. F. T. van
A1  - Bongaerts, Johannes
A1  - Maurer, Karl-Heinz
A1  - Lalk, Michael
A1  - Schweder, Thomas
A1  - Hecker, Michael
A1  - Voigt, Birgit
T1  - Bacillus pumilus reveals a remarkably high resistance to hydrogen peroxide provoked oxidative stress
JF  - PLOS one
N2  - Bacillus pumilus is characterized by a higher oxidative stress resistance than other comparable industrially relevant Bacilli such as B. subtilis or B. licheniformis. In this study the response of B. pumilus to oxidative stress was investigated during a treatment with high concentrations of hydrogen peroxide at the proteome, transcriptome and metabolome level. Genes/proteins belonging to regulons, which are known to have important functions in the oxidative stress response of other organisms, were found to be upregulated, such as the Fur, Spx, SOS or CtsR regulon. Strikingly, parts of the fundamental PerR regulon responding to peroxide stress in B. subtilis are not encoded in the B. pumilus genome. Thus, B. pumilus misses the catalase KatA, the DNA-protection protein MrgA or the alkyl hydroperoxide reductase AhpCF. Data of this study suggests that the catalase KatX2 takes over the function of the missing KatA in the oxidative stress response of B. pumilus. The genome-wide expression analysis revealed an induction of bacillithiol (Cys-GlcN-malate, BSH) relevant genes. An analysis of the intracellular metabolites detected high intracellular levels of this protective metabolite, which indicates the importance of bacillithiol in the peroxide stress resistance of B. pumilus.
Y1  - 2014
U6  - http://dx.doi.org/10.1371/journal.pone.0085625
SN  - 1932-6203
VL  - 9
IS  - 1
PB  - PLOS
CY  - San Francisco
ER  - 
TY  - JOUR
A1  - Almajhdi, Fahad N.
A1  - Senger, Tilo
A1  - Amer, Haitham M.
A1  - Gissmann, Lutz
A1  - Öhlschläger, Peter
T1  - Design of a highly effective therapeutic HPV16 E6/E7-specific DNA vaccine: optimization by different ways of sequence rearrangements (Shuffling)
JF  - PLOS one
N2  - Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16) is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism.
Y1  - 2014
U6  - http://dx.doi.org/10.1371/journal.pone.0113461
SN  - 1932-6203
VL  - 11
IS  - 9
PB  - PLOS
CY  - San Francisco
ER  -