Division and adaptation to host nutritional environment of apicomplexan parasites depend on apicoplast lipid metabolic plasticity and host organelles remodelling

AbstractApicomplexan parasites are unicellular eukaryotes responsible for major human diseases including malaria and toxoplasmosis. Apicomplexan parasites must obtain and combine lipids both from host cell scavenging andde novosynthesis to maintain parasite propagation and survival within their human host. Major questions on the actual role for each lipid source or how these are regulated upon fluctuating host nutritional conditions remain unanswered. Characterization of an apicoplast acyltransferase TgATS2, shows that the apicoplast provides local (lyso)phosphatidic acid balance, which is required for the recruitment of a novel dynamin (TgDrpC) critical during parasite cytokinesis. Disruption of TgATS2 led parasites to shift metabolic lipid acquisition fromde novosynthesis towards host scavenging. Importantly, both lipid scavenging andde novosynthesis pathways exhibit major metabolic and cellular plasticity upon sensing host lipid-deprived environments through concomitant (i) up-regulation ofde novofatty acid synthesis capacities in the apicoplast, and (ii) parasite-driven host cell remodelling to generate multi-membrane-bound structures from host organelles that are imported towards the parasite.

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Characterization of the parasite-host cell interactions involved inTheileria parvasporozoite invasion of bovine lymphocytes

Parasitology ◽

10.1017/s0031182000082032 ◽

1996 ◽

Vol 113 (3) ◽

pp. 267-277 ◽

Cited By ~ 8

Author(s):

M. K. Shaw

Keyword(s):

Host Cell ◽

De Novo ◽

Experimental Conditions ◽

Surface Molecules ◽

Lymphocyte Surface ◽

Host Cell Interactions ◽

Host Cell Surface ◽

Ph Dependent ◽

Bovine Lymphocytes

SUMMARYSporozoite invasion of bovine lymphocytes byTheileria parvais a pH-dependent process that occurs without the need forde novoprotein synthesis. The process was inhibited by RGD(S) peptides, fibronectin and, in the presence of serum, by antibodies reactive with fibronectin. Invasion was also blocked by a range of sulphated glycoconjugates, but treatment of lymphocytes with heparitinase did not inhibit entry. Enzymic modifications of the lymphocyte surface demonstrated that trypsin-insensitive glycoproteins containingO- andN-linked carbohydrates as well as phospholipase-sensitive molecules on the host cell surface were critical to sporozoite entry. Modification of the lymphocyte surface with NEM and DTT had only marginal effects on sporozoite binding but blocked parasite internalization. Invasion was also blocked by several antibodies which cross-reacted with sporozoite surface molecules. While only a few experimental conditions specifically blocked sporozoite binding, a wider range of reagents and treatments inhibited parasite entry. The reasons for this are discussed in terms of the nature of the zippering process that facilitates sporozoite internalization.

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Comprehensive Single Cell Analyses of the Nutritional Environment of Intracellular Salmonella enterica

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.624650 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jennifer Röder ◽

Pascal Felgner ◽

Michael Hensel

Keyword(s):

Host Cell ◽

Salmonella Enterica ◽

Nutrient Supply ◽

Host Cells ◽

Direct Access ◽

Uptake System ◽

Bacterial Proliferation ◽

Membrane Compartments ◽

Membrane Bound ◽

Nutritional Environment

The facultative intracellular pathogen Salmonella enterica Typhimurium (STM) resides in a specific membrane-bound compartment termed the Salmonella-containing vacuole (SCV). STM is able to obtain all nutrients required for rapid proliferation, although being separated from direct access to host cell metabolites. The formation of specific tubular membrane compartments, called Salmonella-induced filaments (SIFs) are known to provides bacterial nutrition by giving STM access to endocytosed material and enabling proliferation. Additionally, STM expresses a range of nutrient uptake system for growth in nutrient limited environments to overcome the nutrition depletion inside the host. By utilizing dual fluorescence reporters, we shed light on the nutritional environment of intracellular STM in various host cells and distinct intracellular niches. We showed that STM uses nutrients of the host cell and adapts uniquely to the different nutrient conditions. In addition, we provide further evidence for improved nutrient supply by SIF formation or presence in the cytosol of epithelial cells, and the correlation of nutrient supply to bacterial proliferation.

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Detrimental effects of alcohol exposure around conception: putative mechanisms

Biochemistry and Cell Biology ◽

10.1139/bcb-2017-0133 ◽

2018 ◽

Vol 96 (2) ◽

pp. 107-116 ◽

Cited By ~ 11

Author(s):

J.I. Kalisch-Smith ◽

K.M. Moritz

Keyword(s):

De Novo ◽

Cell Lineage ◽

Alcohol Exposure ◽

Acid Synthesis ◽

Early Embryo ◽

Epigenetic Reprogramming ◽

Reproductive Age ◽

Interesting Candidate ◽

Uterine Environment ◽

Nutritional Environment

In western countries, alcohol consumption is widespread in women of reproductive age, and in binge quantities. These countries also continue to have high incidences of unplanned pregnancies, with women often reported to cease drinking after discovering their pregnancy. This suggests the early embryo may be highly exposed to the detrimental effects of alcohol during the periconception period. The periconception and pre-implantation windows, which include maturation of the oocyte, fertilisation, and morphogenesis of the pre-implantation embryo, are particularly sensitive times of development. Within the oviduct and uterus, the embryo is exposed to a unique nutritional environment to facilitate its development and establish de-novo expression of the genome through epigenetic reprogramming. Alcohol has wide-ranging effects on cellular stress, as well as hormonal, and nutrient signalling pathways, which may affect the development and metabolism of the early embryo. In this review, we summarise the adverse developmental outcomes of early exposure to alcohol (prior to implantation in animal models) and discuss the potential mechanisms for these outcomes that may occur within the protected oviductal and uterine environment. One interesting candidate is reduced retinoic acid synthesis, as it is implicated in the control of epigenetic reprogramming and cell lineage commitment, processes that have adverse consequences for the formation of the placenta, and subsequently, fetal programming.

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Triacylglycerol synthesis in goat mammary gland. Factors influencing the esterification of fatty acids synthesized de novo

Biochemical Journal ◽

10.1042/bj2200521 ◽

1984 ◽

Vol 220 (2) ◽

pp. 521-527 ◽

Cited By ~ 15

Author(s):

H O Hansen ◽

I Grunnet ◽

J Knudsen

Keyword(s):

Fatty Acids ◽

Mammary Gland ◽

Fatty Acid ◽

De Novo ◽

Acid Synthesis ◽

Diacylglycerol Acyltransferase ◽

Exogenous Fatty Acid ◽

Triacylglycerol Synthesis ◽

Membrane Bound

ATP alone had no effect on incorporation of fatty acids synthesized de novo and membrane-bound diacylglycerol into triacylglycerol. Combined addition of ATP and Mg2+ totally inhibits incorporation of fatty acids synthesized de novo and stimulated incorporation of membrane-bound diacylglycerol. ATP, Mg2+ and glycerol 3-phosphate stimulate incorporation of fatty acids synthesized de novo into triacylglycerol, but inhibited the incorporation of membrane-bound diacylglycerol. Diacylglycerol generated in situ was shown to be superior to diacylglycerols preloaded on the membrane as substrate for the diacylglycerol acyltransferase. A model is proposed to explain the effect of absorbed exogenous fatty acid on fatty acid synthesis de novo in goat mammary gland.

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Genetic Characterization of Accumulation of Polyhydroxyalkanoate from Styrene in Pseudomonas putida CA-3

Applied and Environmental Microbiology ◽

10.1128/aem.71.8.4380-4387.2005 ◽

2005 ◽

Vol 71 (8) ◽

pp. 4380-4387 ◽

Cited By ~ 30

Author(s):

Niall D. O'Leary ◽

Kevin E. O'Connor ◽

Patrick Ward ◽

Miriam Goff ◽

Alan D. W. Dobson

Keyword(s):

Fatty Acid ◽

Pseudomonas Putida ◽

Fatty Acid Synthesis ◽

De Novo ◽

Acyl Carrier Protein ◽

Functional Characterization ◽

Random Mutagenesis ◽

Acid Synthesis ◽

Sole Source

ABSTRACT Pseudomonas putida CA-3 is capable of accumulating medium-chain-length polyhydroxyalkanoates (MCL-PHAs) when growing on the toxic pollutant styrene as the sole source of carbon and energy. In this study, we report on the molecular characterization of the metabolic pathways involved in this novel bioconversion. With a mini-Tn5 random mutagenesis approach, acetyl-coenzyme A (CoA) was identified as the end product of styrene metabolism in P. putida CA-3. Amplified flanking-region PCR was used to clone functionally expressed phenylacetyl-CoA catabolon genes upstream from the sty operon in P. putida CA-3, previously reported to generate acetyl-CoA moieties from the styrene catabolic intermediate, phenylacetyl-CoA. However, the essential involvement of a (non-phenylacetyl-CoA) catabolon-encoded 3-hydroxyacyl-CoA dehydrogenase is also reported. The link between de novo fatty acid synthesis and PHA monomer accumulation was investigated, and a functionally expressed 3-hydroxyacyl-acyl carrier protein-CoA transacylase (phaG) gene in P. putida CA-3 was identified. The deduced PhaG amino acid sequence shared >99% identity with a transacylase from P. putida KT2440, involved in 3-hydroxyacyl-CoA MCL-PHA monomer sequestration from de novo fatty acid synthesis under inorganic nutrient-limited conditions. Similarly, with P. putida CA-3, maximal phaG expression was observed only under nitrogen limitation, with concomitant PHA accumulation. Thus, β-oxidation and fatty acid de novo synthesis appear to converge in the generation of MCL-PHA monomers from styrene in P. putida CA-3. Cloning and functional characterization of the pha locus, responsible for PHA polymerization/depolymerization is also reported and the significance and future prospects of this novel bioconversion are discussed.

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Entry, infection, replication, and egress of human polyomaviruses: an update

Canadian Journal of Microbiology ◽

10.1139/cjm-2016-0519 ◽

2017 ◽

Vol 63 (3) ◽

pp. 193-211 ◽

Cited By ~ 10

Author(s):

Soumen Bhattacharjee ◽

Sutanuka Chattaraj

Keyword(s):

Viral Infection ◽

Host Cell ◽

Decisive Role ◽

Host Protein ◽

Host Animal ◽

Dna Viruses ◽

The Family ◽

Host Cell Surface ◽

Membrane Bound

Polyomaviruses (PyVs), belonging to the family Polyomaviridae, are a group of small, nonenveloped, double-stranded, circular DNA viruses widely distributed in the vertebrates. PyVs cause no apparent disease in adult laboratory mice but cause a wide variety of tumors when artificially inoculated into neonates or semipermissive animals. A few human PyVs, such as BK, JC, and Merkel cell PyVs, have been unequivocally linked to pathogenesis under conditions of immunosuppression. Infection is thought to occur early in life and persists for the lifespan of the host. Over evolutionary time scales, it appears that PyVs have slowly co-evolved with specific host animal lineages. Host cell surface glycoproteins and glycolipids seem to play a decisive role in the entry stage of viral infection and in channeling the virions to specific intracellular membrane-bound compartments and ultimately to the nucleus, where the genomes are replicated and packaged for release. Therefore the transport of the infecting virion or viral genome to this site of multiplication is an essential process in productive viral infection as well as in latent infection and transformation. This review summarizes the major findings related to the characterization of the nature of the interactions between PyV and host protein and their impact in host cell invasion.

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Cobalamin (vitamin B12) biosynthesis: functional characterization of the Bacillus megaterium cbi genes required to convert uroporphyrinogen III into cobyrinic acid a,c-diamide

Biochemical Journal ◽

10.1042/bj3350167 ◽

1998 ◽

Vol 335 (1) ◽

pp. 167-173 ◽

Cited By ~ 27

Author(s):

Evelyne RAUX ◽

Anne LANOIS ◽

Alain RAMBACH ◽

Martin J. WARREN ◽

Claude THERMES

Keyword(s):

Vitamin B12 ◽

Bacillus Megaterium ◽

De Novo ◽

Functional Characterization ◽

Acid Synthesis ◽

Coli Strain ◽

E Coli ◽

Cobyric Acid

The function of individual genes of the Bacillus megaterium cobI operon genes in cobalamin (vitamin B12) biosynthesis was investigated by their ability to complement defined Salmonella typhimurium cob mutants. This strategy confirmed the role of cbiA, -D, -F, -J, -L and cysGA. Furthermore the operon as a whole was used to restore corrin biosynthesis in Escherichia coli, which, although closely related to S. typhimurium, does not possess the CobI pathway. When the B. megaterium cob operon was cloned into a plasmid and transformed into an E. coli strain containing the S. typhimurium cbiP, it conferred upon the host strain the ability to make the cobyric acid de novo. However, cobyric acid synthesis was observed only when the strain was grown anaerobically. Derivatives of the corrin-producing E. coli strain were constructed in which genes of the B. megaterium cob operon had been inactivated. These strains were used to demonstrate that, whereas B. megaterium cbiD, -G and -X are essential for cobyric acid synthesis, the cbiW and -Y genes could be deleted without detriment to cobyric acid production in E. coli.

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Nitrogen sourcing during viral infection of marine cyanobacteria

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1901856116 ◽

2019 ◽

Vol 116 (31) ◽

pp. 15590-15595 ◽

Cited By ~ 9

Author(s):

Jacob R. Waldbauer ◽

Maureen L. Coleman ◽

Adriana I. Rizzo ◽

Kathryn L. Campbell ◽

John Lotus ◽

...

Keyword(s):

Host Cell ◽

Isotope Labeling ◽

De Novo ◽

Building Blocks ◽

Acid Synthesis ◽

Host Protein ◽

Dependent Manner ◽

Host Proteins ◽

Amino Acid Synthesis ◽

Progeny Phage

The building blocks of a virus derived from de novo biosynthesis during infection and/or catabolism of preexisting host cell biomass, and the relative contribution of these 2 sources has important consequences for understanding viral biogeochemistry. We determined the uptake of extracellular nitrogen (N) and its biosynthetic incorporation into both virus and host proteins using an isotope-labeling proteomics approach in a model marine cyanobacterium Synechococcus WH8102 infected by a lytic cyanophage S-SM1. By supplying dissolved N as 15N postinfection, we found that proteins in progeny phage particles were composed of up to 41% extracellularly derived N, while proteins of the infected host cell showed almost no isotope incorporation, demonstrating that de novo amino acid synthesis continues during infection and contributes specifically and substantially to phage replication. The source of N for phage protein synthesis shifted over the course of infection from mostly host derived in the early stages to more medium derived later on. We show that the photosystem II reaction center proteins D1 and D2, which are auxiliary metabolic genes (AMGs) in the S-SM1 genome, are made de novo during infection in an apparently light-dependent manner. We also identified a small set of host proteins that continue to be produced during infection; the majority are homologs of AMGs in S-SM1 or other viruses, suggesting selective continuation of host protein production during infection. The continued acquisition of nutrients by the infected cell and their utilization for phage replication are significant for both evolution and biogeochemical impact of viruses.

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Comprehensive single cell analyses of the nutritional environment of intracellular Salmonella enterica

10.1101/2020.11.01.364018 ◽

2020 ◽

Author(s):

Jennifer Röder ◽

Pascal Felgner ◽

Michael Hensel

Keyword(s):

Host Cell ◽

Salmonella Enterica ◽

Nutrient Supply ◽

Host Cells ◽

Direct Access ◽

Uptake System ◽

Bacterial Proliferation ◽

Membrane Compartment ◽

Membrane Bound ◽

Nutritional Environment

AbstractThe facultative intracellular pathogen Salmonella enterica Typhimurium (STM) resides in a specific membrane-bound compartment termed the Salmonella-containing vacuole (SCV). STM is able to obtain all nutrients required for rapid proliferation, although being separated from direct access to host cell metabolites. The formation of specific tubular membrane compartment, called Salmonella-induced filaments (SIFs) are known to provides bacterial nutrition by giving STM access to endocytosed material and enabling proliferation. Additionally, STM expresses a range of nutrient uptake system for growth in nutrient limited environments to overcome the nutrition depletion inside the host. By utilizing dual fluorescence reporters, we shed light on the nutritional environment of intracellular STM in various host cells and distinct intracellular niches. We showed that STM uses nutrients of the host cell and adapts uniquely to the different nutrient conditions. In addition, we provide further evidence for improved nutrient supply by SIF formation or presence in the cytosol of epithelial cells, and the correlation of nutrient supply to bacterial proliferation.

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