Pathogen Effects on Energy Metabolism in Host Cells

2014 ◽  
pp. 376-401
Keyword(s):  
2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Pingdong Liang ◽  
Karina Tuz ◽  
Oscar Juarez

Thrita ◽  
2020 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mohammad Taghi Taghipour ◽  
Reihaneh Nameni ◽  
Mehrad Taghipour ◽  
Fereshteh Ghorat

Background: The increased use of antibiotics has led to the frequent occurrence of resistant bacterial strains᾽ infections and increased side effects. It is inevitable that medicinal plants and their good antimicrobial activities for controlling and curing different infectious diseases is always a salient feature of various investigations. Also, understanding the plant species in the light of the Holy Quran, religious texts, and the sacred books could make a useful contribution to studying two significant plants used as ancient and reliable medicines. Objectives: The present research used two plants for medicinal products to evaluate their antimicrobial activity. Ziziphus spina-christi (sider) is a medicinal and traditional plant and ethanol and methanol extracts of its leaves have been used against some bacterial and viral infections. Another herbal remedy is Tamarix aphylla with the local name of Ghaz, as the largest known species of Tamarix. The stem smoke of Tamarix aphylla is used by people in the desert area as an antibiotic and antimicrobial agent. Methods: The leaves of Ziziphus spina-christi and Tamarix aphylla were collected to extract their flavonoids and alkaloids using methanol and ethanol, respectively. Moreover, in the process of extraction, powdered and dried leaves by using disc diffusion testing and undiluted neat solution were prepared. Results: The extracted phytochemicals exhibited antimicrobial activity of the two plants through alkaloids and flavonoids as secondary metabolites. Substantial influences on impairing the energy metabolism weakened microbial growth, resulting in the fat formation and protein inhibition. Conclusions: It was concluded that flavonoids and alkaloids from Ziziphus spina-christi and Tamarix aphylla leaves have antimicrobial potential. On the other hand, the process of cell division can be affected by alkaloids that are bound to DNA. Also, flavonoids bind to DNA and RNA, resulting in impairing energy metabolism causing the weakened growth of the microbe affecting protein inhibition and fat formation. Viral cell walls are made up of proteins. Coronavirus spike proteins and viral membrane fusions are wonderful molecules. Through binding to the host cell surface receptor, coronaviruses enter host cells and then fuse the host and viral membranes. Through precipitating the protein components, tannins in Ziziphus spina-christi behave as detoxifying agents by inhibiting their growth.


2018 ◽  
Vol 200 (10) ◽  
Author(s):  
Saroj Poudel ◽  
Daniel R. Colman ◽  
Kathryn R. Fixen ◽  
Rhesa N. Ledbetter ◽  
Yanning Zheng ◽  
...  

ABSTRACTNitrogenase catalyzes the reduction of dinitrogen (N2) using low-potential electrons from ferredoxin (Fd) or flavodoxin (Fld) through an ATP-dependent process. Since its emergence in an anaerobic chemoautotroph, this oxygen (O2)-sensitive enzyme complex has evolved to operate in a variety of genomic and metabolic backgrounds, including those of aerobes, anaerobes, chemotrophs, and phototrophs. However, whether pathways of electron delivery to nitrogenase are influenced by these different metabolic backgrounds is not well understood. Here, we report the distribution of homologs of Fds, Flds, and Fd-/Fld-reducing enzymes in 359 genomes of putative N2fixers (diazotrophs). Six distinct lineages of nitrogenase were identified, and their distributions largely corresponded to differences in the host cells' ability to integrate O2or light into energy metabolism. The predicted pathways of electron transfer to nitrogenase in aerobes, facultative anaerobes, and phototrophs varied from those in anaerobes at the levels of Fds/Flds used to reduce nitrogenase, the enzymes that generate reduced Fds/Flds, and the putative substrates of these enzymes. Proteins that putatively reduce Fd with hydrogen or pyruvate were enriched in anaerobes, while those that reduce Fd with NADH/NADPH were enriched in aerobes, facultative anaerobes, and anoxygenic phototrophs. The energy metabolism of aerobic, facultatively anaerobic, and anoxygenic phototrophic diazotrophs often yields reduced NADH/NADPH that is not sufficiently reduced to drive N2reduction. At least two mechanisms have been acquired by these taxa to overcome this limitation and to generate electrons with potentials capable of reducing Fd. These include the bifurcation of electrons or the coupling of Fd reduction to reverse ion translocation.IMPORTANCENitrogen fixation supplies fixed nitrogen to cells from a variety of genomic and metabolic backgrounds, including those of aerobes, facultative anaerobes, chemotrophs, and phototrophs. Here, using informatics approaches applied to genomic data, we show that pathways of electron transfer to nitrogenase in metabolically diverse diazotrophic taxa have diversified primarily in response to host cells' acquired ability to integrate O2or light into their energy metabolism. The acquisition of two key enzyme complexes enabled aerobic and facultatively anaerobic phototrophic taxa to generate electrons of sufficiently low potential to reduce nitrogenase: the bifurcation of electrons via the Fix complex or the coupling of Fd reduction to reverse ion translocation via theRhodobacternitrogen fixation (Rnf) complex.


2019 ◽  
Author(s):  
Julia María Coronas-Serna ◽  
Arthur Louche ◽  
María Rodríguez-Escudero ◽  
Morgane Roussin ◽  
Paul R.C. Imbert ◽  
...  

ABSTRACTBrucella species are facultative intracellular Gram-negative bacteria relevant to animal and human health. Their ability to establish an intracellular niche and subvert host cell pathways to their advantage depends on the delivery of bacterial effector proteins through a type IV secretion system. Brucella Toll/Interleukin-1 Receptor (TIR)-domain-containing proteins BtpA (also known as TcpB) and BtpB are among such effectors. Although divergent in primary sequence, they interfere with Toll-like receptor (TLR) signaling to inhibit the innate immune responses. However, the molecular mechanisms implicated still remain unclear. To gain insight into the functions of BtpA and BtpB, we expressed them in the budding yeast Saccharomyces cerevisiae as a eukaryotic cell model. We found that both effectors were cytotoxic and that their respective TIR domains were necessary and sufficient for yeast growth inhibition. Growth arrest was concomitant with actin depolymerization, endocytic block and a general decrease in kinase activity in the cell, suggesting a failure in energetic metabolism. Indeed, levels of ATP and NAD+ were low in yeast cells expressing BtpA and BtpB TIR domains, consistent with the recently described enzymatic activity of some TIR domains as NAD+ hydrolases. In human epithelial cells, both BtpA and BtpB expression reduced intracellular total NAD levels. In infected cells, both BtpA and BtpB contributed to reduction of total NAD, indicating that their NAD+ hydrolase functions are active intracellularly during infection. Overall, combining the yeast model together with mammalian cells and infection studies our results show that BtpA and BtpB modulate energy metabolism in host cells through NAD+ hydrolysis, assigning a novel role for these TIR domain-containing effectors in Brucella pathogenesis.


2021 ◽  
Author(s):  
Jiaqi Fu ◽  
Mowei Zhou ◽  
Marina A Gritsenko ◽  
Ernesto S. Nakayasu ◽  
Lei Song ◽  
...  

The intracellular pathogen Legionella pneumophila delivers more than 330 effectors into host cells by its Dot/Icm secretion system. Those effectors direct the biogenesis of the Legionella-containing vacuole (LCV) that permits its intracellular survival and replication. It has long been documented that the LCV is associated with mitochondria and a number of Dot/Icm effectors have been shown to target to this organelle. Yet, the biochemical function and host cell target of most of these effectors remain unknown. Here, we found that the Dot/Icm substrate Ceg3 (Lpg0080) is a mono-ADP-ribosyltransferase that localizes to the mitochondria in host cells where it attacks ADP/ATP translocases by ADP-ribosylation, and blunts their ADP/ATP exchange activity. The modification occurs on the second arginine residue in the -RRRMMM- element, which is conserved among all known ADP/ATP carriers from different organisms. Our results reveal modulation of host energy metabolism as a virulence mechanism for L. pneumophila.


mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Shuna Cui ◽  
Minghui Li ◽  
Rabeay Y. A. Hassan ◽  
Anna Heintz-Buschart ◽  
Junsong Wang ◽  
...  

ABSTRACT Candida albicans adapts to various conditions in different body niches by regulating gene expression, protein synthesis, and metabolic pathways. These adaptive reactions not only allow survival but also influence the interaction with host cells, which is governed by the composition and structure of the fungal cell wall. Numerous studies had shown linkages between mitochondrial functionality, cell wall integrity and structure, and pathogenicity. Thus, we decided to inhibit single complexes of the respiratory chain of C. albicans and to analyze the resultant interaction with macrophages via their phagocytic activity. Remarkably, inhibition of the fungal bc1 complex by antimycin A increased phagocytosis, which correlated with an increased accessibility of β-glucans. To contribute to mechanistic insights, we performed metabolic studies, which highlighted significant changes in the abundance of constituents of the plasma membrane. Collectively, our results reinforce the strong linkage between fungal energy metabolism and other components of fungal physiology, which also determine the vulnerability to immune defense reactions. IMPORTANCE The yeast Candida albicans is one of the major fungal human pathogens, for which new therapeutic approaches are required. We aimed at enhancements of the phagocytosis efficacy of macrophages by targeting the cell wall structure of C. albicans, as the coverage of the β-glucan layer by mannans is one of the immune escape mechanisms of the fungus. We unambiguously show that inhibition of the fungal bc1 complex correlates with increased accessibilities of β-glucans and improved phagocytosis efficiency. Metabolic studies proved not only the known direct effects on reactive oxygen species (ROS) production and fermentative pathways but also the clear downregulation of the ergosterol pathway and upregulation of unsaturated fatty acids. The changed composition of the plasma membrane could also influence the interaction with the overlying cell wall. Thus, our work highlights the far-reaching relevance of energy metabolism, indirectly also for host-pathogen interactions, without affecting viability.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shiyu Li ◽  
Shuting Liu ◽  
Zhenning Dai ◽  
Qian Zhang ◽  
Yichao Xu ◽  
...  

AbstractLong-term studies have shown that virus infection affects the energy metabolism of host cells, which mainly affects the function of mitochondria and leads to the hydrolysis of ATP in host cells, but it is not clear how virus infection participates in mitochondrial energy metabolism in host cells. In our study, HUVEC cells were infected with HSV-1, and the differentially expressed genes were obtained by microarray analysis and data analysis. The viral gene encoding protein UL16 was identified to interact with host protein ANT2 by immunoprecipitation and mass spectrometry. We also reported that UL16 transfection promoted oxidative phosphorylation of glucose and significantly increased intracellular ATP content. Furthermore, UL16 was transfected into the HUVEC cell model with mitochondrial dysfunction induced by d-Gal, and it was found that UL16 could restore the mitochondrial function of cells. It was first discovered that viral protein UL16 could enhance mitochondrial function in mammalian cells by promoting mitochondrial metabolism. This study provides a theoretical basis for the prevention and treatment of mitochondrial dysfunction or the pathological process related to mitochondrial dysfunction.


Author(s):  
W.A. Jacob ◽  
R. Hertsens ◽  
A. Van Bogaert ◽  
M. De Smet

In the past most studies of the control of energy metabolism focus on the role of the phosphorylation potential ATP/ADP.Pi on the regulation of respiration. Studies using NMR techniques have demonstrated that the concentrations of these compounds for oxidation phosphorylation do not change appreciably throughout the cardiac cycle and during increases in cardiac work. Hence regulation of energy production by calcium ions, present in the mitochondrial matrix, has been the object of a number of recent studies.Three exclusively intramitochondnal dehydrogenases are key enzymes for the regulation of oxidative metabolism. They are activated by calcium ions in the low micromolar range. Since, however, earlier estimates of the intramitochondnal calcium, based on equilibrium thermodynamic considerations, were in the millimolar range, a physiological correlation was not evident. The introduction of calcium-sensitive probes fura-2 and indo-1 made monitoring of free calcium during changing energy metabolism possible. These studies were performed on isolated mitochondria and extrapolation to the in vivo situation is more or less speculative.


Author(s):  
H.M. Mazzone ◽  
W.F. Engler ◽  
G. Wray ◽  
A. Szirmae ◽  
J. Conroy ◽  
...  

Viral inclusion bodies isolated from infected pest insects are being evaluated by the U.S. Dept. of Agriculture as biological insecticides against their hosts. Our research on these inclusion bodies constitutes part of an effort to support their approval by the Environmental Protection Agency as insect control agents. The inclusion bodies in this study are polyhedral in shape and contain rod-shaped viral particles. When ingested by pest insects, the inclusion bodies are broken down in the insect gut and release the viral particles which infect and multiply in the nuclei of host cells. These viruses are termed nucleopolyhedrosis viruses (NPV) and are representatives of the baculoviruses (Wildy, P. 1971 IN J.L. Melnick, ed., Monographs in Virology, vol. 5, S.Karger, New York).


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