scholarly journals A Mucoralean White Collar-1 Photoreceptor Controls Virulence by Regulating an Intricate Gene Network during Host Interactions

2021 ◽  
Vol 9 (2) ◽  
pp. 459
Author(s):  
Carlos Pérez-Arques ◽  
María Isabel Navarro-Mendoza ◽  
Laura Murcia ◽  
Carlos Lax ◽  
Marta Sanchis ◽  
...  
Keyword(s):  
Unknown Function ◽  
Gene Network ◽  
White Collar ◽  
Network Clustering ◽  
Phagocytic Cells ◽  
Traditional Role ◽  
Pathogenic Potential ◽  
Virulence Potential ◽  
Fungal Genes

Mucolares are an ancient group of fungi encompassing the causal agents for the lethal infection mucormycosis. The high lethality rates, the emerging character of this disease, and the broad antifungal resistance of its causal agents are mucormycosis features that are alarming clinicians and researchers. Thus, the research field around mucormycosis is currently focused on finding specific weaknesses and targets in Mucorales for developing new treatments. In this work, we tested the role of the white-collar genes family in the virulence potential of Mucor lusitanicus. Study of the three genes of this family, mcwc-1a, mcwc-1b, and mcwc-1c, resulted in a marked functional specialization, as only mcwc-1a was essential to maintain the virulence potential of M. lusitanicus. The traditional role of wc-1 genes regulating light-dependent responses is a thoroughly studied field, whereas their role in virulence remains uncharacterized. In this work, we investigated the mechanism involving mcwc-1a in virulence from an integrated transcriptomic and functional approach during the host–pathogen interaction. Our results revealed mcwc-1a as a master regulator controlling an extensive gene network. Further dissection of this gene network clustering its components by type of regulation and functional criteria disclosed a multifunctional mechanism depending on diverse pathways. In the absence of phagocytic cells, mcwc-1a controlled pathways related to cell motility and the cytoskeleton that could be associated with the essential tropism during tissue invasion. After phagocytosis, several oxidative response pathways dependent on mcwc-1a were activated during the germination of M. lusitanicus spores inside phagocytic cells, which is the first stage of the infection. The third relevant group of genes involved in virulence and regulated by mcwc-1a belonged to the “unknown function,” indicating that new and hidden pathways are involved in virulence. The unknown function category is especially pertinent in the study of mucormycosis, as it is highly enriched in specific fungal genes that represent the most promising targets for developing new antifungal compounds. These results unveil a complex multifunctional mechanism used by wc-1 genes to regulate the pathogenic potential in Mucorales that could also apply to other fungal pathogens.

scholarly journals A Mucoralean White Collar-1 Photoreceptor Controls Virulence by Regulating an Intricate Gene-Network during Host Interactions.

2020 ◽  
Author(s):  
Carlos Pérez Arques ◽  
María Isabel Navarrro Mendoza ◽  
Laura Murcia ◽  
Marta Sanchis ◽  
Javier Capilla ◽  
...  
Keyword(s):  
Unknown Function ◽  
Gene Network ◽  
White Collar ◽  
Network Clustering ◽  
Phagocytic Cells ◽  
Traditional Role ◽  
Pathogenic Potential ◽  
Virulence Potential ◽  
Fungal Genes

Mucolares are an ancient group of fungi encompassing the causal agents for the lethal infection mucormycosis. The high lethality rates, the emerging character of this disease, and the broad antifungal resistance of its causal agents are mucormycosis features alarming clinicians and researchers. Thus, the research field around mucormycosis is currently focused on finding specific weaknesses and targets in Mucorales for developing new treatments against mucormycosis. In this work, we tested the role of the white-collar genes family in the virulence potential of Mucor lusitanicus. In this regard, the study of the role in virulence of the three genes of this family, mcwc-1a, mcwc-1b, and mcwc-1c, resulted in a marked functional specialization, as only mcwc-1a was essential to maintain the virulence potential of M. lusitanicus. The traditional role of wc-1 genes regulating light-dependent responses is a thoroughly studied field, whereas their role in virulence remains uncharacterized. In this work, we investigated the mechanism involving mcwc-1a in virulence from an integrated transcriptomic and functional approach during the host-pathogen interaction. Our results revealed mcwc-1a as a master regulator controlling an extensive gene-network. Further dissection of this gene-network clustering its components by type of regulation and functional criteria disclosed a multifunctional mechanism depending on diverse pathways. In the absence of phagocytic cells, mcwc-1a controlled pathways related to cell motility and cytoskeleton that could be associated with the essential tropism during tissue invasion. After phagocytosis, several oxidative responding pathways dependent on mcwc-1a were activated during the germination of M. lusitanicus spore inside of phagocytic cells, which is the first stage of the infection. The third relevant group of genes involved in virulence and regulated by mcwc-1a belonged to the “unknown function,” indicating that new and hidden pathways are involved in virulence. The unknown function category is especially pertinent in the study of mucormycosis, as it is highly enriched in specific fungal genes that represent the most promising targets for developing new antifungal compounds. These results essentially unveil a complex multifunctional mechanism used by wc-1 genes to regulate the pathogenic potential in Mucorales that could also apply to other fungal pathogens.

scholarly journals Mucor circinelloidesThrives inside the Phagosome through an Atf-Mediated Germination Pathway

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Carlos Pérez-Arques ◽  
María Isabel Navarro-Mendoza ◽  
Laura Murcia ◽  
Carlos Lax ◽  
Pablo Martínez-García ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Network ◽  
Mucor Circinelloides ◽  
Extracellular Proteins ◽  
Antifungal Drugs ◽  
Host Cells ◽  
Molecular Processes ◽  
Phagocytic Cells ◽  
Content Type ◽  
Fungal Genes

ABSTRACTMucormycosis is an emerging fungal infection that is often lethal due to the ineffectiveness of current therapies. Here, we have studied the first stage of this infection—the germination ofMucor circinelloidesspores inside phagocytic cells—from an integrated transcriptomic and functional perspective. A relevant fungal gene network is remodeled in response to phagocytosis, being enriched in crucial functions to survive and germinate inside the phagosome, such as nutritional adaptation and response to oxidative stress. Correspondingly, the phagocytic cells induced a specific proinflammatory and apoptotic response to the pathogenic strain. Deletion of fungal genes encoding putative transcription factors (atf1,atf2, andgcn4), extracellular proteins (chi1andpps1), and an aquaporin (aqp1) revealed that these genes perform important roles in survival following phagocytosis, germination inside the phagosome, and virulence in mice.atf1andatf2play a major role in these pathogenic processes, since their mutants showed the strongest phenotypes and both genes control a complex gene network of secondarily regulated genes, includingchi1andaqp1. These new insights into the initial phase of mucormycosis define genetic regulators and molecular processes that could serve as pharmacological targets.IMPORTANCEMucorales are a group of ancient saprophytic fungi that cause neglected infectious diseases collectively known as mucormycoses. The molecular processes underlying the establishment and progression of this disease are largely unknown. Our work presents a transcriptomic study to unveil theMucor circinelloidesgenetic network triggered in fungal spores in response to phagocytosis by macrophages and the transcriptional response of the host cells. Functional characterization of differentially expressed fungal genes revealed three transcription factors and three extracellular proteins essential for the fungus to survive and germinate inside the phagosome and to cause disease in mice. Two of the transcription factors, highly similar to activating transcription factors (ATFs), coordinate a complex secondary gene response involved in pathogenesis. The significance of our research is in characterizing the initial stages that lead to evasion of the host innate immune response and, in consequence, the dissemination of the infection. This genetic study offers possible targets for novel antifungal drugs against these opportunistic human pathogens.

Questions on the role of biofilms for the adaptation of microorganisms to unfavorable environmental factors by the example of P. aeruginosa

2020 ◽  
Vol 99 (4) ◽  
pp. 379-383
Author(s):  
Vasily N. Afonyushkin ◽  
N. A. Donchenko ◽  
Ju. N. Kozlova ◽  
N. A. Davidova ◽  
V. Yu. Koptev ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Environmental Factors ◽  
Barrier Function ◽  
Infectious Agent ◽  
Antagonistic Activity ◽  
The Body ◽  
Main Function ◽  
Pathogenic Potential ◽  
The Face

Pseudomonas aeruginosa is a widely represented species of bacteria possessing of a pathogenic potential. This infectious agent is causing wound infections, fibrotic cystitis, fibrosing pneumonia, bacterial sepsis, etc. The microorganism is highly resistant to antiseptics, disinfectants, immune system responses of the body. The responses of a quorum sense of this kind of bacteria ensure the inclusion of many pathogenicity factors. The analysis of the scientific literature made it possible to formulate four questions concerning the role of biofilms for the adaptation of P. aeruginosa to adverse environmental factors: Is another person appears to be predominantly of a source an etiological agent or the source of P. aeruginosa infection in the environment? Does the formation of biofilms influence on the antibiotic resistance? How the antagonistic activity of microorganisms is realized in biofilm form? What is the main function of biofilms in the functioning of bacteria? A hypothesis has been put forward the effect of biofilms on the increase of antibiotic resistance of bacteria and, in particular, P. aeruginosa to be secondary in charcter. It is more likely a biofilmboth to fulfill the function of storing nutrients and provide topical competition in the face of food scarcity. In connection with the incompatibility of the molecular radii of most antibiotics and pores in biofilm, biofilm is doubtful to be capable of performing a barrier function for protecting against antibiotics. However, with respect to antibodies and immunocompetent cells, the barrier function is beyond doubt. The biofilm is more likely to fulfill the function of storing nutrients and providing topical competition in conditions of scarcity of food resources.

FAITH–BASED COMMUNITIES AND POLITICS IN DULLSTROOM-EMNOTWENI: LOCAL STORIES OF IDENTITY

2016 ◽  
Vol 1 (1) ◽  
pp. 45-57 ◽  
Author(s):  
Christina Landman
Keyword(s):  
Higher Education ◽  
Service Delivery ◽  
Special Focus ◽  
Traditional Role ◽  
Cultural Conflicts ◽  
Local Identities ◽  
Political Interests ◽  
Local Municipality ◽  
The Face

A majority of the black community of Dullstroom-Emnotweni in the Mpumalanga highveld in the east of South Africa trace their descent back to the southern Ndebele of the so-called ‘Mapoch Gronden’, who lost their land in the 1880s to become farm workers on their own land. A hundred years later, in 1980, descendants of the ‘Mapoggers’ settled in the newly built ‘township’ of Dullstroom, called Sakhelwe, finding jobs on the railways or as domestic workers. Oral interviews with the inhabitants of Sakhelwe – a name eventually abandoned in favour of Dullstroom- Emnotweni – testify to histories of transition from landowner to farmworker to unskilled labourer. The stories also highlight cultural conflicts between people of Ndebele, Pedi and Swazi descent and the influence of decades of subordination on local identities. Research projects conducted in this and the wider area of the eMakhazeni Local Municipality reveal the struggle to maintain religious, gender and youth identities in the face of competing political interests. Service delivery, higher education, space for women and the role of faith-based organisations in particular seem to be sites of contestation. Churches and their role in development and transformation, where they compete with political parties and state institutions, are the special focus of this study. They attempt to remain free from party politics, but are nevertheless co-opted into contra-culturing the lack of service delivery, poor standards of higher education and inadequate space for women, which are outside their traditional role of sustaining an oppressed community.

Pathogenic potential of Parabacteroides distasonis revealed in a splenic abscess case: a truth unfolded

2020 ◽  
Vol 13 (12) ◽  
pp. e236701
Author(s):  
Anitha Gunalan ◽  
Rakhi Biswas ◽  
Balamurugan Sridharan ◽  
Thirthar Palanivelu Elamurugan
Keyword(s):  
Abdominal Pain ◽  
Case Report ◽  
Antimicrobial Therapy ◽  
Splenic Abscess ◽  
Rare Entity ◽  
Normal Flora ◽  
Pathogenic Role ◽  
Pathogenic Potential ◽  
Open Splenectomy

Splenic abscess is a rare entity, however if unrecognised or left untreated, it is invariably fatal. We herein report a case of splenic abscess in a 40-year-old man presenting with fever, left-sided abdominal pain, altered sensorium and vomiting. On clinical examination, hepatosplenomegaly was noted and the ultrasound of the abdomen showed multiple hypoechoic regions in the upper pole of spleen, and the diagnosis of splenic abscess was made. The patient received antimicrobial therapy and underwent an open splenectomy with full recovery. Pus aspirated from the splenic abscess grew an unusual organism named Parabacteroides distasonis. In the literature, there are only a few recorded cases of P. distasonis causing splenic abscess. Through this case report, we would like to emphasise the pathogenic role of P. distasonis in causing clinical disease, as this organism is typically known to constitute a part of the normal flora.

scholarly journals Evaluation of the role of CD47 in sickle cell disease

2021 ◽  
Author(s):  
Basmah Eldakhakhny ◽  
Hadeel Al Sadoun ◽  
Nehal Bin Taleb ◽  
Dunya Ahmed Nori ◽  
Nawal Helmi ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Annexin V ◽  
Cell Disease ◽  
Phagocytic Cells ◽  
Surface Marker Expression ◽  
Inflammatory Phenotype ◽  
Healthy Control ◽  
Cell Surface Marker Expression ◽  
Pro Inflammatory Cytokines

AbstractCD47 is a self-marker expressed on the surface of RBCs and work to prevent the process of phagocytosis. SIRPα is the ligand of CD47 that is expressed on the surface of phagocytic cells, such as macrophages, to control the removal of dead/diseased cells. This study aimed to examine the expression of CD47 on RBCs and SIRPα on PBMC cells in SCD patients and the apoptosis of SCD RBCs. We also measured the levels of pro-inflammatory cytokines in SCD patients and correlated it with the cell surface marker expression of CD47 and SIRPα to determine whether CD47 and/or SIRPα played a role in promoting the pro-inflammatory phenotype in SCD. Whole blood samples were drawn from SCD patients, and healthy control and PBMC were isolated and stained with SIRPα. Change in CD47, apoptosis by annexin V marker, and pro-inflammatory cytokines were measured and correlation among these variants was determined. The expression of CD47 was significantly decreased and the apoptosis was increased in RBCs of SCD patients. A higher level of pro-inflammatory cytokines, IL-6 and IL-1β, was found in SCD patients and IL-1β was found to be inversely correlated with SIRPα expression. Our data showed that CD47 of erythrocytes of SCD samples is reduced and that the apoptosis is increased in those patients. Based on the role of CD47, we suggest that increased apoptosis in SCD would be impacted by the reduced level of CD47. An inverse relationship was found between SIRPα marker on PBMC and the increased production of pro-inflammatory cytokines in SCD.

Applications of Energy Beams in Material and Device Processing

1983 ◽  
Vol 23 ◽  
Author(s):  
G.J. Galvin ◽  
L.S. Hung ◽  
J.W. Mayer ◽  
M. Nastasi
Keyword(s):  
Ion Beam ◽  
High Energy ◽  
Ion Beams ◽  
Traditional Role ◽  
Near Surface ◽  
Device Processing ◽  
Composition Modification ◽  
Directed Energy ◽  
Transistor Fabrication

ABSTRACTEnergetic ion beams used outside the traditional role of ion implantation are considered for semiconductor applications involving interface modification for self-aligned silicide contacts, composition modification for formation of buried oxide layers in Si on insulator structures and reduced disorder in high energy ion beam annealing for buried collectors in transistor fabrication. In metals, aside from their use in modification of the composition of near surface regions, energetic ion beams are being investigated for structural modification in crystalline to amorphous transitions. Pulsed beams of photons and electrons are used as directed energy sources in rapid solidification. Here, we consider the role of temperature gradients and impurities in epitaxial growth of silicon.

scholarly journals A comprehensive p75 neurotrophin receptor gene network and pathway analyses identifying new target genes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Antti Sajanti ◽  
Seán B. Lyne ◽  
Romuald Girard ◽  
Janek Frantzén ◽  
Tomi Rantamäki ◽  
...  
Keyword(s):  
Gene Network ◽  
Brain Plasticity ◽  
Initial Point ◽  
Cellular Damage ◽  
Neurotrophin Receptor ◽  
Signaling Networks ◽  
Network Analyses ◽  
Pathway Analyses ◽  
General Response

Abstract P75 neurotrophic receptor (p75NTR) is an important receptor for the role of neurotrophins in modulating brain plasticity and apoptosis. The current understanding of the role of p75NTR in cellular adaptation following pathological insults remains blurred, which makes p75NTR’s related signaling networks an interesting and challenging initial point of investigation. We identified p75NTR and related genes through extensive data mining of a PubMed literature search including published works related to p75NTR from the past 20 years. Bioinformatic network and pathway analyses of identified genes (n = 235) were performed using ReactomeFIViz in Cytoscape based on the highly reliable Reactome functional interaction network algorithm. This approach merges interactions extracted from human curated pathways with predicted interactions from machine learning. Genome-wide pathway analysis showed total of 16 enriched hierarchical clusters. A total of 278 enriched single pathways were also identified (p < 0.05, false discovery rate corrected). Gene network analyses showed multiple known and new targets in the p75NTR gene network. This study provides a comprehensive analysis and investigation into the current knowledge of p75NTR signaling networks and pathways. These results also identify several genes and their respective protein products as involved in the p75NTR network, which have not previously been clearly studied in this pathway. These results can be used to generate novel hypotheses to gain a greater understanding of p75NTR in acute brain injuries, neurodegenerative diseases and general response to cellular damage.

scholarly journals Adaptation, Ecology, and Evolution of the Halophilic Stromatolite ArchaeonHalococcus hamelinensisInferred through Genome Analyses

Archaea ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Reema K. Gudhka ◽  
Brett A. Neilan ◽  
Brendan P. Burns
Keyword(s):  
Unknown Function ◽  
Energy Production ◽  
Extreme Environment ◽  
Evolutionary Significance ◽  
Base Pairs ◽  
Protein Coding ◽  
Inorganic Ion ◽  
Damage Repair ◽  
Genome Analyses

Halococcus hamelinensiswas the first archaeon isolated from stromatolites. These geomicrobial ecosystems are thought to be some of the earliest known on Earth, yet, despite their evolutionary significance, the role of Archaea in these systems is still not well understood. Detailed here is the genome sequencing and analysis of an archaeon isolated from stromatolites. The genome ofH. hamelinensisconsisted of 3,133,046 base pairs with an average G+C content of 60.08% and contained 3,150 predicted coding sequences or ORFs, 2,196 (68.67%) of which were protein-coding genes with functional assignments and 954 (29.83%) of which were of unknown function. Codon usage of theH. hamelinensisgenome was consistent with a highly acidic proteome, a major adaptive mechanism towards high salinity. Amino acid transport and metabolism, inorganic ion transport and metabolism, energy production and conversion, ribosomal structure, and unknown function COG genes were overrepresented. The genome ofH. hamelinensisalso revealed characteristics reflecting its survival in its extreme environment, including putative genes/pathways involved in osmoprotection, oxidative stress response, and UV damage repair. Finally, genome analyses indicated the presence of putative transposases as well as positive matches of genes ofH. hamelinensisagainst various genomes of Bacteria, Archaea, and viruses, suggesting the potential for horizontal gene transfer.

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