scholarly journals Role of acuK in Control of Iron Acquisition and Gluconeogenesis in Talaromyces marneffei

2021 ◽  
Vol 7 (10) ◽  
pp. 798
Author(s):  
Artid Amsri ◽  
Juthatip Jeenkeawpieam ◽  
Panwarit Sukantamala ◽  
Monsicha Pongpom

Talaromyces marneffei is a dimorphic pathogenic fungus causing opportunistic infection in immunocompromised patients. It is a facultative intracellular pathogen and is usually found inside the host macrophages during infection. Alternative carbons and iron are the important nutrients associated with intracellular survival and pathogenesis of T. marneffei. This study reported the importance of the transcription factor AcuK in control of gluconeogenesis and iron acquisition in T. marneffei. Deletion of acuK gene in T. marneffei resulted in retardation of growth and germination in both mold and yeast phases. Microscopically, ΔacuK showed double nuclei hyphae. However, the yeast cells showed normal morphology. The ΔacuK failed to grow in iron-limiting conditions. Additionally, it could not grow in a medium containing gluconeogenic carbon sources. Moreover, ΔacuK showed higher susceptibility to macrophage killing than the wild type. These results demonstrated that AcuK controlled both iron acquisition and gluconeogenesis, and it could contribute to the pathogenicity of this fungus.

2019 ◽  
Vol 58 (3) ◽  
pp. 351-361 ◽  
Author(s):  
Jiao Feng ◽  
Liya He ◽  
Xing Xiao ◽  
Zhiwen Chen ◽  
Chunmei Chen ◽  
...  

Abstract Talaromyces marneffei (T. marneffei), which used to be known as Penicillium marneffei, is the causative agent of the fatal systemic mycosis known as talaromycosis. For the purpose of understanding the role of methylcitrate cycle in the virulence of T. marneffei, we generated MCD deletion (ΔMCD) and complementation (ΔMCD+) mutants of T. marneffei. Growth in different carbon sources showed that ΔMCD cannot grow on propionate media and grew slowly on the valerate, valine, methionine, isoleucine, cholesterol, and YNB (carbon free) media. The macrophage killing assay showed that ΔMCD was attenuated in macrophages of mice in vitro, especially at the presence of propionate. Finally, virulence studies in a murine infection experiment revealed attenuated virulence of the ΔMCD, which indicates MCD is essential for T. marneffei virulence in the host. This experiment laid the foundation for the further study of the specific mechanisms underlying the methylcitrate cycle of T. marneffei and may provide suitable targets for new antifungals.


2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Aner Gurvitz

Caenorhabditis elegansF09E10.3 (dhs-25) was identified as encoding a 3-oxoacyl-thioester reductase, potentially of the mitochondrial type 2 fatty acid synthase (FASII) system. Mitochondrial FASII is a relatively recent discovery in metazoans, and the relevance of this process to animal physiology has not been elucidated. A good animal model to study the role of FASII is the nematodeC. elegans. However, the components of nematode mitochondrial FASII have hitherto evaded positive identification. The nematode F09E10.3 protein was ectopically expressed without an additional mitochondrial targeting sequence inSaccharomyces cerevisiaemutant cells lacking the homologous mitochondrial FASII enzyme 3-oxoacyl-ACP reductase Oar1p. These yeastoar1Δmutants are unable to respire, grow on nonfermentable carbon sources, or synthesize sufficient levels of lipoic acid. Mutant yeast cells producing a full-length mitochondrial F09E10.3 protein containedNAD+-dependent 3-oxoacyl-thioester reductase activity and resembled the corresponding mutant overexpressing native Oar1p for the above-mentioned phenotype characteristics. This is the first identification of a metazoan 3-oxoacyl-thioester reductase (see Note Added in Proof).


2000 ◽  
Vol 68 (7) ◽  
pp. 4225-4237 ◽  
Author(s):  
Marta Feldmesser ◽  
Yvonne Kress ◽  
Phyllis Novikoff ◽  
Arturo Casadevall

ABSTRACT To produce chronic infection, microbial pathogens must escape host immune defenses. Infection with the human pathogenic fungusCryptococcus neoformans is typically chronic. To understand the mechanism by which C. neoformans survives in tissue after the infection of immunocompetent hosts, we systematically studied the course of pulmonary infection in mice by electron microscopy. The macrophage was the primary phagocytic cell at all times of infection, but neutrophils also ingested yeast. Alveolar macrophages rapidly internalized yeast cells after intratracheal infection, and intracellular yeast cells were noted at all times of infection from 2 h through 28 days. However, the proportion of yeast cells in the intracellular and extracellular spaces varied with the time of infection. Early in infection, yeast cells were found predominantly in the intracellular compartment. A shift toward extracellular predominance occurred by 24 h that was accompanied by macrophage cytotoxicity and disruption. Later in infection, intracellular persistence in vivo was associated with replication, residence in a membrane-bound phagosome, polysaccharide accumulation inside cells, and cytotoxicity to macrophages, despite phagolysosomal fusion. Many phagocytic vacuoles with intracellular yeast had discontinuous membranes. Macrophage infection resulted in cells with a distinctive appearance characterized by large numbers of vacuoles filled with polysaccharide antigen. Similar results were observed in vitro using a macrophage-like cell line. Our results show that C. neoformans is a facultative intracellular pathogen in vivo. Furthermore, our observations suggest that C. neoformansoccupies a unique niche among the intracellular pathogens whereby survival in phagocytic cells is accompanied by intracellular polysaccharide production.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jing Gao ◽  
Paula J. M. van Kleeff ◽  
Ka Wan Li ◽  
Albertus H. de Boer

AbstractTo date, few phenotypes have been described for Arabidopsis 14-3-3 mutants or the phenotypes showing the role of 14-3-3 in plant responding to abiotic stress. Although one member of the 14-3-3 protein family (14-3-3 omicron) was shown to be involved in the proper operation of Fe acquisition mechanisms at physiological and gene expression levels in Arabidopsis thaliana, it remains to be explored whether other members play a role in regulating iron acquisition. To more directly and effectively observe whether members of 14-3-3 non-epsilon group have a function in Fe-deficiency adaptation, three higher order quadruple KOs, kappa/lambda/phi/chi (klpc), kappa/lambda/upsilon/nu(klun), and upsilon/nu/phi/chi (unpc) were generated and studied for physiological analysis in this study. The analysis of iron-utilization efficiency, root phenotyping, and transcriptional level of Fe-responsive genes suggested that the mutant with kl background showed different phenotypes from Wt when plants suffered Fe starved, while these phenotypes were absent in the unpc mutant. Moreover, the absence of the four 14-3-3 isoforms in the klun mutant has a clear impact on the 14-3-3 interactome upon Fe deficiency. Dynamics of 14-3-3-client interactions analysis showed that 27 and 17 proteins differentially interacted with 14-3-3 in Wt and klun roots caused by Fe deficiency, respectively. Many of these Fe responsive proteins have a role in glycolysis, oxidative phosphorylation and TCA cycle, the FoF1-synthase and in the cysteine/methionine synthesis. A clear explanation for the observed phenotypes awaits a more detailed analysis of the functional aspects of 14-3-3 binding to the target proteins identified in this study.


2021 ◽  
Author(s):  
Lauren E. Manck ◽  
Jiwoon Park ◽  
Benjamin J. Tully ◽  
Alfonso M. Poire ◽  
Randelle M. Bundy ◽  
...  

AbstractIt is now widely accepted that siderophores play a role in marine iron biogeochemical cycling. However, the mechanisms by which siderophores affect the availability of iron from specific sources and the resulting significance of these processes on iron biogeochemical cycling as a whole have remained largely untested. In this study, we develop a model system for testing the effects of siderophore production on iron bioavailability using the marine copiotroph Alteromonas macleodii ATCC 27126. Through the generation of the knockout cell line ΔasbB::kmr, which lacks siderophore biosynthetic capabilities, we demonstrate that the production of the siderophore petrobactin enables the acquisition of iron from mineral sources and weaker iron-ligand complexes. Notably, the utilization of lithogenic iron, such as that from atmospheric dust, indicates a significant role for siderophores in the incorporation of new iron into marine systems. We have also detected petrobactin, a photoreactive siderophore, directly from seawater in the mid-latitudes of the North Pacific and have identified the biosynthetic pathway for petrobactin in bacterial metagenome-assembled genomes widely distributed across the global ocean. Together, these results improve our mechanistic understanding of the role of siderophore production in iron biogeochemical cycling in the marine environment wherein iron speciation, bioavailability, and residence time can be directly influenced by microbial activities.


1975 ◽  
Vol 28 (3) ◽  
pp. 301 ◽  
Author(s):  
MJ Hynes

Mutants of Apergillus nidulanswith lesions in a gene, areA (formerly called amdT), have been isolated by a variety of different selection methods. The areA mutants show a range of pleiotropic growth responses to a number of compounds as sole nitrogen sources, but are normal in utilization of carbon sources. The levels of two amidase enzymes as well as urease have been investigated in the mutants and have been shown to be affected by this gene. Most of the areA mutants have much lower amidase-specific activities when grown in ammonium-containing medium, compared with mycelium incubated in medium la9king a nitrogen source. Some of the areA. mutants do not show derepression of urease upon relief of ammonium repression. The dominance relationships of areA alleles have been investigated in� heterozygous diploids, and these studies lend support to the proposal that areA codes for a positively acting regulatory product. One of the new areA alleles is partially dominant to areA + and areA102. This may be a result of negative complementation or indicate that areA has an additional negative reiuIatory function. Investigation.of various amdR; areA double mutants has led to the conclusion that amdR and areA participate in independent regulatory circuits in the control of acetamide utilizatiol1. Studies on an amdRc; areA.double mutant indicate that areA is involved in derepression of acetamidase upon relief of ammo.nium repression.


2015 ◽  
Vol 51 (12) ◽  
pp. 2450-2453 ◽  
Author(s):  
Dae-Soo Yang ◽  
Min Young Song ◽  
Kiran Pal Singh ◽  
Jong-Sung Yu

The exact role of iron in catalyzing oxygen reduction reaction in both alkaline and acidic media is portrayed with unique platelet ordered mesoporous carbon prepared using Fe-phthalocyanine as iron, nitrogen and carbon sources.


1990 ◽  
Vol 10 (2) ◽  
pp. 549-560 ◽  
Author(s):  
S A Nadin-Davis ◽  
A Nasim

We have further investigated the function of the ras1 and byr1 genes, which were previously shown to be critical for sexual differentiation in fission yeast cells. Several physiological similarities between strains containing null alleles of these genes supports the idea that ras1 and byr1 are functionally closely related. Furthermore, we have found that byr1 is allelic to ste1, one of at least 10 genes which when mutated can cause sterility. Since ras1 had previously been found to be allelic to ste5, both ras and byr genes are now clearly shown to be a part of the ste gene family, thus confirming their close functional relationship. The observation that the mating-type loci could overcome the sporulation block of ras1 and byr1 mutant strains prompted investigation of the role of the ras-byr pathway in the induction of the mating-type gene transcripts upon nitrogen starvation. By Northern analysis of RNA preparations from strains carrying wild-type or mutant ras1 alleles and grown to different stages of the growth cycle, we have shown that ras1 plays an important role in inducing the Pi transcript of the mating-type loci and the mei3 gene transcript. These observations provide a molecular basis for the role of the ste gene family, including ras1 and byr1, in meiosis and indicate that further characterization of other ste genes would be very useful for elucidating the mechanism of ras1 function in fission yeast cells.


Genetics ◽  
1987 ◽  
Vol 116 (4) ◽  
pp. 531-540
Author(s):  
Aileen K W Taguchi ◽  
Elton T Young

ABSTRACT The alcohol dehydrogenase II (ADH2) gene of the yeast, Saccharomyces cerevisiae, is not transcribed during growth on fermentable carbon sources such as glucose. Growth of yeast cells in a medium containing only nonfermentable carbon sources leads to a marked increase or derepression of ADH2 expression. The recessive mutation, adr6-1, leads to an inability to fully derepress ADH2 expression and to an inability to sporulate. The ADR6 gene product appears to act directly or indirectly on ADH2 sequences 3' to or including the presumptive TATAA box. The upstream activating sequence (UAS) located 5' to the TATAA box is not required for the Adr6- phenotype. Here, we describe the isolation of a recombinant plasmid containing the wild-type ADR6 gene. ADR6 codes for a 4.4-kb RNA which is present during growth both on glucose and on nonfermentable carbon sources. Disruption of the ADR6 transcription unit led to viable cells with decreased ADHII activity and an inability to sporulate. This indicates that both phenotypes result from mutations within a single gene and that the adr6-1 allele was representative of mutations at this locus. The ADR6 gene mapped to the left arm of chromosome XVI at a site 18 centimorgans from the centromere.


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