scholarly journals Amino Acid Sensing and Assimilation by the Fungal Pathogen Candida albicans in the Human Host

Pathogens ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 5
Author(s):  
Fitz Gerald S. Silao ◽  
Per O. Ljungdahl
Keyword(s):  
Amino Acids ◽  
Candida Albicans ◽  
Amino Acid ◽  
Fungal Pathogens ◽  
Close Association ◽  
Amino Acid Uptake ◽  
Nutrient Sensing ◽  
Acid Uptake ◽  
Uptake And Metabolism

Nutrient uptake is essential for cellular life and the capacity to perceive extracellular nutrients is critical for coordinating their uptake and metabolism. Commensal fungal pathogens, e.g., Candida albicans, have evolved in close association with human hosts and are well-adapted to using diverse nutrients found in discrete host niches. Human cells that cannot synthesize all amino acids require the uptake of the “essential amino acids” to remain viable. Consistently, high levels of amino acids circulate in the blood. Host proteins are rich sources of amino acids but their use depends on proteases to cleave them into smaller peptides and free amino acids. C. albicans responds to extracellular amino acids by pleiotropically enhancing their uptake and derive energy from their catabolism to power opportunistic virulent growth. Studies using Saccharomyces cerevisiae have established paradigms to understand metabolic processes in C. albicans; however, fundamental differences exist. The advent of CRISPR/Cas9-based methods facilitate genetic analysis in C. albicans, and state-of-the-art molecular biological techniques are being applied to directly examine growth requirements in vivo and in situ in infected hosts. The combination of divergent approaches can illuminate the biological roles of individual cellular components. Here we discuss recent findings regarding nutrient sensing with a focus on amino acid uptake and metabolism, processes that underlie the virulence of C. albicans.

scholarly journals The Candida albicans GAP Gene Family Encodes Permeases Involved in General and Specific Amino Acid Uptake and Sensing

2011 ◽  
Vol 10 (9) ◽  
pp. 1219-1229 ◽  
Author(s):  
Lucie Kraidlova ◽  
Griet Van Zeebroeck ◽  
Patrick Van Dijck ◽  
Hana Sychrová
Keyword(s):  
Amino Acids ◽  
Candida Albicans ◽  
Amino Acid ◽  
Fungal Pathogens ◽  
Signal Transduction Pathway ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Amino Acid Permease ◽  
Content Type ◽  
Six Genes

ABSTRACTTheSaccharomyces cerevisiaegeneral amino acid permease Gap1 (ScGap1) not only mediates the uptake of most amino acids but also functions as a receptor for the activation of protein kinase A (PKA). Fungal pathogens can colonize different niches in the host, each containing various levels of different amino acids and sugars. TheCandida albicansgenome contains six genes homologous to theS. cerevisiae GAP1. The expression of these six genes inS. cerevisiaeshowed that the products of all sixC. albicansgenes differ in their transport capacities.C. albicansGap2 (CaGap2) is the true orthologue ofScGap1 as it transports all tested amino acids. The otherCaGap proteins have narrower substrate specificities thoughCaGap1 andCaGap6 transport several structurally unrelated amino acids.CaGap1,CaGap2, andCaGap6 also function as sensors. Upon detecting some amino acids, e.g., methionine, they are involved in a rapid activation of trehalase, a downstream target of PKA. Our data show thatCaGAPgenes can be functionally expressed inS. cerevisiaeand thatCaGap permeases communicate to the intracellular signal transduction pathway similarly toScGap1.

scholarly journals Coordination of the Uptake and Metabolism of Amino Acids in Mycobacterium tuberculosis-Infected Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Qingkui Jiang ◽  
Lanbo Shi
Keyword(s):  
Amino Acids ◽  
Mycobacterium Tuberculosis ◽  
Amino Acid ◽  
Macrophage Polarization ◽  
Amino Acid Uptake ◽  
Metabolic Reprogramming ◽  
Glutamine Metabolism ◽  
Acid Uptake ◽  
System L ◽  
Uptake And Metabolism

Macrophage polarization to the M1-like phenotype, which is critical for the pro-inflammatory and antimicrobial responses of macrophages against intracellular pathogens, is associated with metabolic reprogramming to the Warburg effect and a high output of NO from increased expression of NOS2. However, there is limited understanding about the uptake and metabolism of other amino acids during M1 polarization. Based on functional analysis of a group of upregulated transporters and enzymes involved in the uptake and/or metabolism of amino acids in Mycobacterium tuberculosis-infected macrophages, plus studies of immune cell activation, we postulate a coherent scheme for amino acid uptake and metabolism during macrophage polarization to the M1-like phenotype. We describe potential mechanisms that the increased arginine metabolism by NOS2 is metabolically coupled with system L transporters LAT1 and LAT2 for the uptake of neutral amino acids, including those that drive mTORC1 signaling toward the M1-like phenotype. We also discuss the underappreciated pleiotropic roles of glutamine metabolism in the metabolic reprogramming of M1-like macrophages. Collectively, our analyses argue that a coordinated amino acid uptake and metabolism constitutes an integral component of the broad metabolic scheme required for macrophage polarization to M1-like phenotype against M. tuberculosis infection. This idea could stimulate future experimental efforts to elucidate the metabolic map of macrophage activation for the development of anti-tuberculosis therapies.

scholarly journals Effect of premature weaning on amino acid uptake by the mammary gland of lactating rats

1981 ◽  
Vol 200 (3) ◽  
pp. 705-708 ◽  
Author(s):  
J R Viña ◽  
I R Puertes ◽  
J Viña
Keyword(s):  
Amino Acids ◽  
Mammary Gland ◽  
Amino Acid ◽  
Amino Acid Uptake ◽  
Mammary Glands ◽  
Acid Uptake ◽  
Gamma Glutamyltransferase ◽  
Gamma Glutamyl ◽  
Lactating Mammary Gland

1. Arteriovenous differences of amino acids across the lactating mammary gland were measured in normal rats and weaned for 4, 5 and 24h. 2. Uptake of amino acids by mammary glands of rats weaned for 5h or more was significantly lower than that of controls. This was not reversed by injection of prolactin. 3. By using ‘unilaterally weaned’ rats we showed that milk accumulation plays an important role in amino acid uptake by mammary gland. 4. gamma-Glutamyltransferase activity was significantly lower in ‘weaned’ glands than in ‘normal’ glands. This provides further support for the hypothesis of the function of the gamma-glutamyl cycle in the mammary gland in vivo.

scholarly journals Involvement of γ-glutamyltransferase in amino-acid uptake by the lactating mammary gland of the rat

1981 ◽  
Vol 194 (1) ◽  
pp. 99-102 ◽  
Author(s):  
J Viña ◽  
I R Puertes ◽  
J M Estrela ◽  
J R Viña ◽  
J L Galbis
Keyword(s):  
Amino Acids ◽  
Mammary Gland ◽  
Amino Acid ◽  
Reduced Glutathione ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Gamma Glutamyltransferase ◽  
Lactating Mammary Gland ◽  
High Concentrations

1. Arteriovenous differences of amino acids across the lactating mammary gland have been measured in normal rats and in rats injected with serine–borate (an inhibitor of gamma-glutamyltransferase). 2. Comparison of the arteriovenous differences show that gamma-glutamyltransferase is involved in amino-acid uptake by the gland. 3. Reduced-glutathione content of isolated acini incubated with high concentrations of amino acids was lower than that of the controls. 4. High concentrations of amino acids had no effect on reduced-glutathione content of isolated acini when serine–borate was added to the incubation medium. 5. The findings provide evidence for the functioning of the gamma-glutamyl cycle in the lactating mammary gland in vivo.

scholarly journals Divergence of Stp1 and Stp2 Transcription Factors in Candida albicans Places Virulence Factors Required for Proper Nutrient Acquisition under Amino Acid Control

2005 ◽  
Vol 25 (21) ◽  
pp. 9435-9446 ◽  
Author(s):  
Paula Martínez ◽  
Per O. Ljungdahl
Keyword(s):  
Amino Acids ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Amino Acid ◽  
Active Form ◽  
Amino Acid Uptake ◽  
Extracellular Proteins ◽  
Proteolytic Processing ◽  
Acid Uptake ◽  
Processed Form

ABSTRACT Candida albicans possesses a plasma membrane-localized sensor of extracellular amino acids. Here, we show that in response to amino acids, this sensor induces the proteolytic processing of two latent transcription factors, Stp1 and Stp2. Processing removes negative regulatory motifs present in the N-terminal domains of these factors. Strikingly, Stp1 and Stp2 exhibit a clear dichotomy in the genes they transactivate. The shorter active form of Stp2 activates genes required for amino acid uptake. The processed form of Stp1 activates genes required for degradation of extracellular protein and uptake of peptides, and cells lacking Stp1 do not express the secreted aspartyl protease SAP2 or the oligopeptide transporter OPT1. Consequently, stp1 null mutants are unable to grow on media with protein as the sole nitrogen source. Cells expressing the STP1* allele that encodes a protein lacking the inhibitory N-terminal domain constitutively express SAP2 and OPT1 even in the absence of extracellular proteins or peptides. Also, we show that Stp1 levels, but not Stp2 levels, are downregulated in the presence of millimolar concentrations of extracellular amino acids. These results define the hierarchy of regulatory mechanisms that differentially control two discrete pathways for the assimilation of nitrogen.

scholarly journals Studies on Aromatic Amino Acid Uptake by Rat Brain in Vivo

1962 ◽  
Vol 237 (3) ◽  
pp. 803-806
Author(s):  
Gordon Guroff ◽  
Sidney Udenfriend
Keyword(s):  
Amino Acid ◽  
Rat Brain ◽  
Aromatic Amino Acid ◽  
Amino Acid Uptake ◽  
Acid Uptake

Gamma-Glutamyl-Amino Acids as Signals for the Hormonal Regulation of Amino Acid Uptake by the Mammary Gland of the Lactating Rat

Neonatology ◽  
1985 ◽  
Vol 48 (4) ◽  
pp. 250-256 ◽  
Author(s):  
Juan R. Viña ◽  
Inmaculada R. Puertes ◽  
Juan B. Montoro ◽  
Guillermo T. Saez ◽  
José Viña
Keyword(s):  
Amino Acids ◽  
Mammary Gland ◽  
Amino Acid ◽  
Hormonal Regulation ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Gamma Glutamyl

Somatostatin inhibits insulin-stimulated amino acid uptake into cultured rat myoblasts

1987 ◽  
Vol 114 (4) ◽  
pp. 470-474 ◽  
Author(s):  
G. S. G. Spencer ◽  
D. J. Hill ◽  
G. J. Garssen ◽  
J. P. G. Williams
Keyword(s):  
Amino Acid ◽  
Nutrient Uptake ◽  
Monolayer Culture ◽  
Amino Acid Uptake ◽  
Inhibitory Effect ◽  
Isobutyric Acid ◽  
Acid Uptake ◽  
Newborn Rat ◽  
Amino Isobutyric Acid

Abstract. The effects of somatostatin on the acute metabolic actions of insulin on newborn rat myoblasts in culture has been examined during monolayer culture. Somatostatin significantly inhibited the insulin-stimulated uptake of [3H]leucine and [3H]amino-isobutyric acid into myoblasts but had no effect on basal (unstimulated) uptake of these two substances. The lowest concentration of somatostatin to have a significant effect was 10 μg/l, and this was apparent in all the experiments undertaken. The inhibitory effect of somatostatin was seen at all effective concentrations of insulin used (0.3–1 U/l). These findings lend support to the concept of an endocrine role for somatostatin in vivo and suggest that a peripheral antagonism may exist between circulating insulin and somatostatin on anabolic processes such as nutrient uptake into cells.

scholarly journals Action of growth hormone in vitro on the net uptake and incorporation into protein of amino acids in muscle from intact rabbits given protein-deficient diets

1976 ◽  
Vol 35 (1) ◽  
pp. 1-10 ◽  
Author(s):  
M. R. Turner ◽  
P. J. Reeds ◽  
K. A. Munday
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Protein Synthesis ◽  
Amino Acid ◽  
De Novo ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Amino Acid Incorporation ◽  
Acid Incorporation

1. Net amino acid uptake, and incorporation into protein have been measured in vitro in the presence and absence of porcine growth hormone (GH) in muscle from intact rabbits fed for 5 d on low-protein (LP), protein-free (PF) or control diets.2. In muscle from control and LP animals GH had no effect on the net amino acid uptake but stimulated amino acid incorporation into protein, although this response was less in LP animals than in control animals.3. In muscle from PF animals, GH stimulated both amino acid incorporation into protein and the net amino acid uptake, a type of response which also occurs in hypophysectomized animals. The magnitude of the effect of GH on the incorporation of amino acids into protein was reduced in muscle from PF animals.4. The effect of GH on the net amino acid uptake in PF animals was completely blocked by cycloheximide; the uptake effect of GH in these animals was dependent therefore on de novo protein synthesis.5. It is proposed that in the adult the role of growth hormone in protein metabolism is to sustain cellular protein synthesis when there is a decrease in the level of substrate amino acids, similar to that which occurs during a short-term fast or when the dietary protein intake is inadequate.

The uptake of amino acids by mouse cells (strain LS) during growth in batch culture and chemostat culture: the influence of cell growth rate

1967 ◽  
Vol 168 (1013) ◽  
pp. 421-438 ◽  
Keyword(s):  
Amino Acids ◽  
Growth Rate ◽  
Amino Acid ◽  
Cell Growth ◽  
Glutamic Acid ◽  
Batch Culture ◽  
Amino Acid Uptake ◽  
Essential Amino Acids ◽  
Growth Yields ◽  
Acid Uptake

The uptake of thirteen essential amino acids by mouse LS cells in suspension culture was determined by bacteriological assay methods. Chemostat continuous-flow cultures were used to determine the effect of different cell growth rates on the quantitative amino acid requirements for growth. The growth yields of the cells ( Y = g cell dry weight produced/g amino acid utilized) were calculated for each of the essential amino acids. A mixture of the non-essential amino acids, serine, alanine and glycine increased the cell yield from the essential amino acids. The growth yields from nearly all the essential amino acids in batch culture were increased when glutamic acid was substituted for the glutamine in the medium. The growth yields from the amino acids in batch culture were much less at the beginning than at the end of the culture. The highest efficiencies of conversion of amino acids to cell material were obtained by chemostat culture. When glutamic acid largely replaced the glutamine in the medium the conversion of amino acid nitrogen to cell nitrogen was 100 % efficient (that is, the theoretical yield was obtained) at the optimum growth rate (cell doubling time, 43 h). The maximum population density a given amino acid mixture will support can be calculated from the data. It is concluded that in several routinely used tissue culture media the cell growth is limited by the amino acid supply. In batch culture glutamine was wasted by (1) its spontaneous decomposition to pyrrolidone carboxylic acid and ammonia, and (2) its enzymic breakdown to glutamic acid and ammonia, but also glutamine was used less efficiently than glutamic acid. Study of the influence of cell growth rate on amino acid uptake rates per unit mass of cells indicated that a marked change in amino acid metabolism occurred at a specific growth rate of 0.4 day -1 (cell doubling time, 43 h). With decrease in specific growth rate below 0.4 day -1 there was a marked stimulation of amino acid uptake rate per cell and essential amino acids were consumed increasingly for functions other than synthesis of cell material.

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