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María Pérez-Burgos Inmaculada García-Romero Miguel A. Valvano Lotte Søgaard Andersen 《Molecular microbiology》2020,113(6):1189-1208
The rod-shaped cells of Myxococcus xanthus, a Gram-negative deltaproteobacterium, differentiate to environmentally resistant spores upon starvation or chemical stress. The environmental resistance depends on a spore coat polysaccharide that is synthesised by the ExoA-I proteins, some of which are part of a Wzx/Wzy-dependent pathway for polysaccharide synthesis and export; however, key components of this pathway have remained unidentified. Here, we identify and characterise two additional loci encoding proteins with homology to enzymes involved in polysaccharide synthesis and export, as well as sugar modification and show that six of the proteins encoded by these loci are essential for the formation of environmentally resistant spores. Our data support that MXAN_3260, renamed ExoM and MXAN_3026, renamed ExoJ, are the Wzx flippase and Wzy polymerase, respectively, responsible for translocation and polymerisation of the repeat unit of the spore coat polysaccharide. Moreover, we provide evidence that three glycosyltransferases (MXAN_3027/ExoK, MXAN_3262/ExoO and MXAN_3263/ExoP) and a polysaccharide deacetylase (MXAN_3259/ExoL) are important for formation of the intact spore coat, while ExoE is the polyisoprenyl-phosphate hexose-1-phosphate transferase responsible for initiating repeat unit synthesis, likely by transferring N-acetylgalactosamine-1-P to undecaprenyl-phosphate. Together, our data generate a more complete model of the Exo pathway for spore coat polysaccharide biosynthesis and export. 相似文献
3.
Ilse Van Gucht Josephina A.N. Meester Jotte Rodrigues Bento Maaike Bastiaansen Jarl Bastianen Ilse Luyckx Lotte Van Den Heuvel Cédric H.G. Neutel Pieter-Jan Guns Mandy Vermont Erik Fransen Melanie H.A.M. Perik Joe Davis Velchev Maaike Alaerts Dorien Schepers Silke Peeters Isabel Pintelon Abdulrahman Almesned Aline Verstraeten 《American journal of human genetics》2021,108(6):1115-1125
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Inke Wallrodt Lotte Jelsbak Lotte Thorndahl Line E. Thomsen Sebastien Lemire John E. Olsen 《PloS one》2013,8(8)
The phage-shock protein PspE and GlpE of the glycerol 3-phosphate regulon of Salmonella enterica serovar Typhimurium are predicted to belong to the class of thiosulfate sulfurtransferases, enzymes that traffic sulfur between molecules. In the present study we demonstrated that the two genes contribute to S. Typhimurium virulence, as a glpE and pspE double deletion strain showed significantly decreased virulence in a mouse model of systemic infection. However, challenge of cultured epithelial cells and macrophages did not reveal any virulence-associated phenotypes. We hypothesized that their contribution to virulence could be in sulfur metabolism or by contributing to resistance to nitric oxide, oxidative stress, or cyanide detoxification. In vitro studies demonstrated that glpE but not pspE was important for resistance to H2O2. Since the double mutant, which was the one affected in virulence, was not affected in this assay, we concluded that resistance to oxidative stress and the virulence phenotype was most likely not linked. The two genes did not contribute to nitric oxid stress, to synthesis of essential sulfur containing amino acids, nor to detoxification of cyanide. Currently, the precise mechanism by which they contribute to virulence remains elusive. 相似文献
6.
Iben B. Bentsen Ida Nielsen Michael Lisby Helena B. Nielsen Souvik Sen Gupta Kamilla Mundbjerg Anni H. Andersen Lotte Bjergbaek 《Nucleic acids research》2013,41(5):3173-3189
To address how eukaryotic replication forks respond to fork stalling caused by strong non-covalent protein–DNA barriers, we engineered the controllable Fob-block system in Saccharomyces cerevisiae. This system allows us to strongly induce and control replication fork barriers (RFB) at their natural location within the rDNA. We discover a pivotal role for the MRX (Mre11, Rad50, Xrs2) complex for fork integrity at RFBs, which differs from its acknowledged function in double-strand break processing. Consequently, in the absence of the MRX complex, single-stranded DNA (ssDNA) accumulates at the rDNA. Based on this, we propose a model where the MRX complex specifically protects stalled forks at protein–DNA barriers, and its absence leads to processing resulting in ssDNA. To our surprise, this ssDNA does not trigger a checkpoint response. Intriguingly, however, placing RFBs ectopically on chromosome VI provokes a strong Rad53 checkpoint activation in the absence of Mre11. We demonstrate that proper checkpoint signalling within the rDNA is restored on deletion of SIR2. This suggests the surprising and novel concept that chromatin is an important player in checkpoint signalling. 相似文献
7.
Lotte Engell-Noerregaard Helle W. Hendel Helle H. Johannesen Louise Alslev Inge Marie Svane 《Cancer immunology, immunotherapy : CII》2013,62(1):17-25
Background
Measurements of tumour metabolism by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) have been successfully applied to monitor tumour response after chemo- and chemo-radiotherapy and may not have the same limitations as other morphological imaging techniques. In this study it is investigated whether FDG-PET might add information on the efficacy of immune therapy.Materials and methods
In a retrospective analysis data from patients with advanced progressive melanoma, treated with DC vaccinations and evaluated by PET/CT scans at baseline as well as after 6 vaccinations were analysed. If a patient achieved stable disease according to RECIST, additional vaccinations were given. The PET scans were evaluated according to EORTC guidelines.Results
PET/CT scans from 13 patients were evaluated. According to RECIST 3 patients achieved stable disease and 10 patients progressed. Interestingly, when evaluated by PET scans 2 patients had partial metabolic response and 1 patient had complete metabolic response of the 2 index lesions even though a new lesion appeared simultaneously. Ten patients were seen to have stable or progressive metabolic disease.Conclusion
By adding PET scans to the CT evaluation of patients treated with DC vaccines, a more detailed picture of the single lesions was found. This seems to improve the clinical evaluation of the treatment. The lack of correlation between the PET and CT scans suggests that some of the increases in target lesions seen in CT scans might be due to oedema or immune-infiltrates and not progression of the disease. Thus, further investigation into the contribution of PET scans to the evaluation of cancer immunotherapy is needed. 相似文献8.
Winfried Boos John S. Parkinson Urs Jenal Jörg Vogel Lotte Søgaard‐Andersen 《Molecular microbiology》2013,88(2):219-221
On November 28, 2012 Alexander (Alex) Böhm, a bacterial geneticist, died at age 41, only a few months after taking up a position as an assistant professor at the LOEWE Center for Synthetic Microbiology in Marburg, Germany. Earlier in 2012 Alex had been diagnosed with an aggressive form of thyroid cancer that left him little time to live his scientific and personal dreams. 相似文献
9.
Zitta B. Harboe Palle Valentiner-Branth Helene Ingels Jeppe N. Rasmussen Peter H. S. Andersen Catherine C. Bjerre David Goldblatt Lindsey Ashton Mitch Haston Helle B. Konradsen Lotte Lambertsen 《PloS one》2013,8(1)
A seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the Danish childhood immunization program (2+1 schedule) in October 2007, followed by PCV13 starting from April 2010. The nationwide incidence of IPD among children younger than 5 years nearly halved after the introduction of PCV7 in the program, mainly due to a decline in IPD caused by PCV7-serotypes. We report the results from a nationwide population-based cohort study of laboratory confirmed IPD cases in children younger than 5 years during October 1, 2007 to December 31, 2010 and describe the characteristics of children suspected to present with a vaccine failure. The period between April 19 and December 31, 2010 was considered a PCV7/PCV13 transitional period, where both vaccines were offered. We identified 45 episodes of IPD caused by a PCV7 serotype (23% of the total number) and 105 (55%) caused by one of the 6 additional serotypes in PCV13. Ten children had received at least one PCV7 dose before the onset of IPD caused by a PCV7 serotype. Seven children were considered to be incompletely vaccinated before IPD, but only three cases fulfilled the criteria of vaccine failure (caused by serotypes 14, 19F and 23F). One case of vaccine failure was observed in a severely immunosuppressed child following three PCV7 doses, and two cases were observed in immunocompetent children following two infant doses before they were eligible for their booster. None of the IPD cases caused by the additional PCV13 serotypes had been vaccinated by PCV13 and there were therefore no PCV13-vaccine failures in the first 8-months after PCV13 introduction in Denmark. 相似文献
10.
Hoeks FW Boon LA Studer F Wolff MO van der Schot F Vrabél P van der Lans RG Bujalski W Manelius A Blomsten G Hjorth S Prada G Luyben KCh Nienow AW 《Journal of industrial microbiology & biotechnology》2003,30(2):118-128
Foam disruption by agitation—the stirring as foam disruption (SAFD) technique—was scaled up to pilot and production scale
using Rushton turbines and an up-pumping hydrofoil impeller, the Scaba 3SHP1. The dominating mechanism behind SAFD—foam entrainment—was
also demonstrated at production scale. The mechanistic model for SAFD defines a fictitious liquid velocity generated by the
(upper) impeller near the dispersion surface, which is correlated with complete foam disruption. This model proved to be scalable,
thus enabling the model to be used for the design of SAFD applications. Axial upward pumping impellers appeared to be more
effective with respect to SAFD than Rushton turbines, as demonstrated by retrofitting a 12,000 l bioreactor, i.e. the triple
Rushton configuration was compared with a mixed impeller configuration from Scaba with a 20% lower ungassed power draw. The
retrofitted impeller configuration allowed 10% more broth without risking excessive foaming. In this way a substantial increase
in the volumetric productivity of the bioreactor was achieved. Design recommendations for the application of SAFD are given
in this paper. Using these recommendations for the design of a 30,000 l scale bioreactor, almost foamless Escherichia coli fermentations were realised.
Electronic Publication 相似文献