scholarly journals The Stringent Response of Mycobacterium tuberculosis Is Required for Long-Term Survival

2000 ◽  
Vol 182 (17) ◽  
pp. 4889-4898 ◽  
Author(s):  
Todd P. Primm ◽  
Susan J. Andersen ◽  
Valerie Mizrahi ◽  
David Avarbock ◽  
Harvey Rubin ◽  
...  
Keyword(s):  
Growth Rate ◽  
Mycobacterium Tuberculosis ◽  
Stringent Response ◽  
Wild Type ◽  
Liquid Media ◽  
Term Survival ◽  
Long Term Survival ◽  
Starvation Conditions

ABSTRACT The stringent response utilizes hyperphosphorylated guanine [(p)ppGpp] as a signaling molecule to control bacterial gene expression involved in long-term survival under starvation conditions. In gram-negative bacteria, (p)ppGpp is produced by the activity of the related RelA and SpoT proteins. Mycobacterium tuberculosis contains a single homolog of these proteins (RelMtb) and responds to nutrient starvation by producing (p)ppGpp. A relMtb knockout strain was constructed in a virulent strain of M. tuberculosis, H37Rv, by allelic replacement. The relMtb mutant displayed a significantly slower aerobic growth rate than the wild type in synthetic liquid media, whether rich or minimal. The growth rate of the wild type was equivalent to that of the mutant when citrate or phospholipid was employed as the sole carbon source. These two organisms also showed identical growth rates within a human macrophage-like cell line. These results suggest that the in vivo carbon source does not represent a stressful condition for the bacilli, since it appears to be utilized in a similar RelMtb-independent manner. In vitro growth in liquid media represents a condition that benefits from RelMtb-mediated adaptation. Long-term survival of therelMtb mutant during in vitro starvation or nutrient run out in normal media was significantly impaired compared to that in the wild type. In addition, the mutant was significantly less able to survive extended anerobic incubation than the wild-type virulent organism. Thus, the RelMtb protein is required for long-term survival of pathogenic mycobacteria under starvation conditions.

Human thymic epithelial cells maintain long-term survival of clonogenic myeloid and erythroid progenitor cells in vitro

2000 ◽  
Vol 111 (1) ◽  
pp. 363-370 ◽  
Author(s):  
Katsuto Takenaka ◽  
Mine Harada ◽  
Tomoaki Fujisaki ◽  
Koji Nagafuji ◽  
Shinichi Mizuno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Progenitor Cells ◽  
Thymic Epithelial Cells ◽  
Erythroid Progenitor ◽  
Term Survival ◽  
Long Term Survival ◽  
Erythroid Progenitor Cells

LONG TERM SURVIVAL OF CRYPTIC VIRUSES IN ASEPTICALLY GROWN IN VITRO PROPAGATED PLANTS

2006 ◽  
pp. 505-510 ◽  
Author(s):  
A. Szego ◽  
P. Ilyes ◽  
E.K. Toth ◽  
L. Potvondi ◽  
N. Lukacs
Keyword(s):  
Term Survival ◽  
Long Term Survival

LONG-TERM SURVIVAL, MORPHOLOGY AND IN VITRO FUNCTION OF ISOLATED PIG ISLETS UNDER DIFFERENT CULTURE CONDITIONS1

1999 ◽  
Vol 67 (12) ◽  
pp. 1533-1541 ◽  
Author(s):  
Daniel Brandhorst ◽  
Heide Brandhorst ◽  
Bernhard J. Hering ◽  
Reinhard G. Bretzel
Keyword(s):  
Term Survival ◽  
Long Term Survival

scholarly journals Rhesus Theta Defensin 1 Promotes Long Term Survival in Systemic Candidiasis by Host Directed Mechanisms

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Virginia Basso ◽  
Dat Q. Tran ◽  
Justin B. Schaal ◽  
Patti Tran ◽  
Yoshihiro Eriguchi ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
Mouse Serum ◽  
Term Survival ◽  
Long Term Survival ◽  
Immunosuppressed Patients ◽  
Time Of Infection

AbstractInvasive candidiasis is an increasingly frequent cause of serious and often fatal infections in hospitalized and immunosuppressed patients. Mortality rates associated with these infections have risen sharply due to the emergence of multidrug resistant (MDR) strains of C. albicans and other Candida spp., highlighting the urgent need of new antifungal therapies. Rhesus theta (θ) defensin-1 (RTD-1), a natural macrocyclic antimicrobial peptide, was recently shown to be rapidly fungicidal against clinical isolates of MDR C. albicans in vitro. Here we found that RTD-1 was rapidly fungicidal against blastospores of fluconazole/caspofungin resistant C. albicans strains, and was active against established C. albicans biofilms in vitro. In vivo, systemic administration of RTD-1, initiated at the time of infection or 24 h post-infection, promoted long term survival in candidemic mice whether infected with drug-sensitive or MDR strains of C. albicans. RTD-1 induced an early (4 h post treatment) increase in neutrophils in naive and infected mice. In vivo efficacy was associated with fungal clearance, restoration of dysregulated inflammatory cytokines including TNF-α, IL-1β, IL-6, IL-10, and IL-17, and homeostatic reduction in numbers of circulating neutrophils and monocytes. Because these effects occurred using peptide doses that produced maximal plasma concentrations (Cmax) of less than 1% of RTD-1 levels required for in vitro antifungal activity in 50% mouse serum, while inducing a transient neutrophilia, we suggest that RTD-1 mediates its antifungal effects in vivo by host directed mechanisms rather than direct fungicidal activity. Results of this study suggest that θ-defensins represent a new class of host-directed compounds for treatment of disseminated candidiasis.

Long-term survival of AT-1 cardiomyocyte grafts in syngeneic myocardium

1993 ◽  
Vol 264 (5) ◽  
pp. H1727-H1733 ◽  
Author(s):  
G. Y. Koh ◽  
M. H. Soonpaa ◽  
M. G. Klug ◽  
L. J. Field
Keyword(s):  
Fusion Gene ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Thymidine Uptake ◽  
Electron Microscopic ◽  
Term Survival ◽  
Long Term Survival

The long-term viability of cardiomyocyte grafts in the adult myocardium was tested. AT-1 cardiomyocytes, a differentiated tumor line derived from transgenic mice expressing an atrial natriuretic factor-simian virus 40 T antigen fusion gene, were grafted directly into the myocardium of syngeneic animals. Viable grafts were detected as long as 4 mo postimplantation. Thymidine uptake studies suggested that the grafted cardiomyocytes retained mitotic activity. The presence of AT-1 cardiomyocyte grafts and the associated myocardial remodeling were not accompanied by overt cardiac arrhythmia. Electron microscopic analyses showed that the majority of the grafts were juxtaposed directly to the host myocardium and were not encapsulated. This study indicates that the myocardium can serve as a stable platform for cells that have been manipulated in vitro and suggests that cardiomyocyte grafts may provide a useful means for the local delivery of recombinant molecules to the heart. The long-term survival of the AT-1 cardiomyocytes in the heart also raises the possibility that similar grafting approaches may be used to replace diseased myocardium.

P5990In vivo tracking of long-term survival of xenogeneic porcine mesenchymal stem cells seeded on tissue-engineered heart valve implanted in sheep

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Gyongyosi ◽  
D Lukovic ◽  
N Pavo ◽  
A Gugerell ◽  
J Winkler ◽  
...  
Keyword(s):  
Reporter Gene ◽  
Insertional Mutagenesis ◽  
Term Survival ◽  
Long Term Survival ◽  
Non Invasive ◽  
Pet Ct ◽  
Valve Implantation

Abstract Background Long-term survival of xenogeneic transplanted cells in adults requires strong immunosuppression and/or encapsulation of the cells to achieve peripheral transplant tolerance. Purpose The aim of our project was to seed decellularized tissue engineered heart valves (TEHV) with xenogeneic (porcine) mesenchymal stem cells (pMSCs) transfected transiently (Lipofectamine) with a positron emission tomography (PET)-reporter gene (pMSC-PETr), followed by implantation as pulmonary valve replacement into sheep without immunosuppression. The fate of the seeded pMSC-PETr was tracked via serial in-vivo non-invasive PET-computed tomography (PET-CT). Methods Static cultivation of TEHV scaffold led to successful ingrowth of the pMSC-PETr. For enabling quantitative assessment of viable pMSC-PETr in the TEHV scaffold after in vivo implantation, vials containing 5x104, 2x105, and 4x105 pMSC-PETr were in vitro mixed with the [18F]-FHBG PET tracer for 1 hr, then the non-bound tracer was washed out and vials were in vitro PET-CT imaged, giving reference values. TEHV-pMSC-PETr were then implanted percutaneously into the pulmonary valve position of sheep (n=4) under general anesthesia, while an additional sheep with no valve implantation served as a control. Ten mCi of [18F]-FHBGPET radiotracer was produced for each procedure and serial PET-CT imaging of the sheep was performed at 3 hr, 24 hr, 2 or 3 weeks, and 5 and 6 months after valve implantation. The study followed the Principles of laboratory animal care. Results PET-CT of vials containing increasing number of pMSC-PETr showed dose-dependent tracer uptake in the transfected cells in vitro (Figure). PET-CT images of the sheep 3 hr after implantation of the TEHV-pMSC-PETr showed a clear signal of transfected cells, with a mean estimated number of viable pMSC-PETr of 5.18±1.19x106. No meaningful decrease of the amount of living cells occurred at 24 hr or 2 or 3 weeks. Interestingly, 5- and 6-month follow-up PET-CT images showed clear in vivo and in vitro (after explantation) PET signals of the pMSC-PETr on TEHV, indicating spontaneous stable transfection of the PET reporter plasmid (insertional mutagenesis). Histology confirmed the survival of the pMSC-PETr at 5 and 6-month after xenogeneic transplantation. Merged immunohistochemistry and fluorescence imaging of anti-pig SLA I and anti-sheep MHC I antibodies and PET-reporter gene (HSV1-tk) suggested in vivo inter-species lateral jump gene transfer between pig MSCs and host sheep cells. Figure 1 Conclusions This is the first report on serial non-invasive in vivo tracking of long-term survival of xenogeneic pMSCs-PETr seeded on TEHVs and percutaneously implanted into the pulmonary position of sheep. Long-term follow-up revealed spontaneous stable transfection of the plasmid PET-reporter gene, which suggests the risk of insertional mutagenesis induced by the plasmid (transposon), and PET-reporter gene shuttle from xenogeneic pig MSCs to sheep cells. Acknowledgement/Funding LifeValve EU project (grant number: 242008)

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