Research Highlights: Gut bacteria share ability to acquire vitamin B12 by “hugging” each other


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Credit: © SPL

Gut bacteria share ability to acquire vitamin B12 by “hugging” each other

  • Mobile genetic elements or MGEs are genetic materials that can move around within a genome or move across different genomes.[1]
  • One popular example of mobile genetic elements in evolutionary context is the transfer of antibiotic resistance genes to another bacteria.
  • Horizontal transfer refers to the transfer of genetic material between organisms rather than the transmission of DNA from parent to offspring.[3]
  • Horizontal transfer of mobile genetic elements can shape the diversity of the human gut microbiome.
  • Mobile genetic elements can encode genes which benefits their host such as providing self-defense or the ability to compete for limited resources.
  • Vitamin B12 is an important nutrient required to enable gut colonization of Bacteriodetes.
  • Bacteriodetes are Gram-negative bacteria found anywhere in gastrointestinal tract, including the mouth and stomach, despite the presence of gastric juices and digestive enzymes.[4]
  • Researchers discovered a distinct type of mobile genetic elements in the Bacteriodetes responsible for the movement and exchange of the genes required for the transport of corrinoids.
  • Corrinoid is cobalt-containing molecule that function as enzyme cofactors in many organisms.[5]
  • An example of corrinoid is vitamin B12 (cobalamin).[6]
  • The newly discovered mobile genetic elements include two distinct groups of conjugative transposons and one group of bacteriophage.
  • Conjugative transposons are elements that can move from one bacterial cell to another through cell to cell contact.[7]
  • Researchers confirmed the activity of two of the conjugative transposons in vitro and in vivo.
  • The study highlights the importance of mobile genetic elements in distribution of corrinoid transporters in gut bacteria.

Sources:

Frye, K. A., Piamthai, V., Hsiao, A., & Degnan, P. H. (2021). Mobilization of vitamin B12 transporters alters competitive dynamics in a human gut microbe. Cell reports, 37(13), 110164. https://doi.org/10.1016/j.celrep.2021.110164

[1] https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/mobile-genetic-elements

[2] https://en.wikipedia.org/wiki/Mobile_genetic_elements

[3] https://en.wikipedia.org/wiki/Horizontal_gene_transfer

[4] https://www.sciencedirect.com/topics/medicine-and-dentistry/bacteroidetes

[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485714

[6] https://en.wikipedia.org/wiki/Vitamin_B12

[7] https://link.springer.com/chapter/10.1007/978-1-4615-6369-3_13

Research Highlights: Microbes with high metabolic activity found in deep, hot subseafloor environment


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Microbes with high metabolic activity found in deep, hot subseafloor environment

  • About 25 percent of the world’s seabed sediment can be found at a depth where temperature is more than 80 °C.
  • Scientists previously proposed that 80 °C is the thermal barrier for life in the strata below the Earth’s surface.
  • Researchers discovered a population of methanogenic and sulfate-reducing organisms in deep buried marine sediment.
  • Methanogenic organisms produce methane as a metabolic byproduct in low oxygen conditions.[1]
  • Sulfate-reducing organisms can perform anaerobic respiration by using sulfate as terminal electron acceptor and reducing it to hydrogen sulfide.[2]
  • The IODP (International Ocean Discovery Program) Expedition 370 drilled and collected sediment cores in the Nankai Trough subduction zone just south of Japan.
  • The Nankai Trough subduction zone can reach temperatures of about 120 °C.
  • Subduction zone is the place where two plates of the Earth come together, one is found over the other.[3]
  • Researchers utilized a considerable suite of radiotracer experiments.
  • Radiotracers is a compound that contains a radioactive element and can be used to study the mechanism of chemical reactions.[4]
  • The small microbes discovered from the Nankai Trough subduction zone survived with high potential cell-specific rates of energy metabolism, similar to the rates in active surface microbes and laboratory cultures.
  • Researchers initially expected that the metabolic rates in the deep subseafloor will be extremely low.
  • The cells appear to expend almost all of their energy to repair damages from the high temperature.
  • At the same time, the cells are forced to balance between supporting themselves at a minimum level near the thermal barrier for life and a rich source of substrates and energy from the reactions of the sedimentary organic matter caused by the high temperature environment.

Sources:

Beulig, F., Schubert, F., Adhikari, R.R. et al. Rapid metabolism fosters microbial survival in the deep, hot subseafloor biosphere. Nat Commun 13, 312 (2022). https://doi.org/10.1038/s41467-021-27802-7

[1] https://en.wikipedia.org/wiki/Methanogen

[2] https://en.wikipedia.org/wiki/Sulfate-reducing_microorganism

[3] https://earthquake.usgs.gov/learn/glossary/?term=subduction%20zone

[4] https://www.iaea.org/topics/radiotracers

Research Highlights: Broccoli Contains Compound That Can Kill Yeast


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green broccoli vegetable on brown wooden table
Photo by Pixabay on Pexels.com

Broccoli Contains Compound That Can Kill Yeast

  • Broccoli is a common edible green plant in the family Brassicaceae with all of the parts eaten as vegetable.[1]
  • A compound called 3,3’-diindolylmethane or DIM can be obtained from the digestion of indole-3-carbinol, found in broccoli.
  • DIM promotes cell death and autophagy in some human cancer.
  • Autophagy refers to the natural process of cell degradation by which unnecessary or non-functional cellular components are removed or recycled.
  • DIM extends lifespan in the yeast called Schizosaccharomyces pombe.
  • S. pombe, often called fission yeast, is a species of yeast used in traditional brewing.[3]
  • However, the way by which DIM promotes cell destruction in humans and extends lifespan in S. pombe are not very well understood.
  • Researchers show that DIM promotes cell destruction in log-phase cells which is dose-dependent.
  • .Log-phase is the period by which cells exponentially increase in number.
  • Researchers discovered that when high concentration of DIM was added, the cell’s nuclear envelope was disrupted and the chromosome tightly packed at an early stage.
  • On the other hand, when low concentration of DIM was added, cells were degraded but did not cause disruption on the nuclear envelope.
  • Cells defective in autophagy were more vulnerable to the low concentration of DIM which suggest the autophagic pathway contributes to the cell’s survival against DIM.
  • Additionally, researchers discovered that the cells with lem2 mutation are more sensitive to DIM.
  • Lem2 is a protein that regulates the size of the cell’s nuclear envelope.[2]
  • The nuclear envelope of cells with lem2 mutation was disrupted even at low DIM concentration.
  • The results highlight the importance of autophagic pathway and nuclear envelope integrity in maintaining cell viability during exposure to low DIM concentration.
  • Researchers speculated that the process of cell death and autophagy induce by DIM are conserved in humans and S. pombe.
  • Future studies are needed to understand more about the DIM being able to induce cell death and autophagy in humans and S. pombe.

Sources:

Emami P, Ueno M (2021) 3,3’-Diindolylmethane induces apoptosis and autophagy in fission yeast. PLoS ONE 16(12): e0255758. https://doi.org/10.1371/journal.pone.0255758

[1] https://en.wikipedia.org/wiki/Broccoli

[2] https://www.nature.com/articles/s41467-019-09623-x

[3] https://en.wikipedia.org/wiki/Schizosaccharomyces_pombe

Research Highlights: Magnesium Helps The Immune System Fight Against Cancer


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clevelandclinic.org

Magnesium Helps The Immune System Fight Against Cancer

  • Magnesium is important in maintaining a healthy body.[1]
  • Magnesium is involved in muscle regulation, nerve function, blood sugar levels, blood pressure, protein production, bone maintenance, and genetic stability.[1]
  • Foods that contain magnesium include legumes, nuts, whole grains, green leafy vegetables, breakfast cereals, yogurt, and certain milk products.[1]
  • The role of magnesium outside the cells in regards to cellular immunity remains unclear.
  • Lymphocyte Function Associated Antigen 1 or LFA-1 is a cell-surface protein found on CD8+ T cells.[2]
  • LFA-1 functions as an adhesion molecule promoting contact between two cells or between a cell and the extracellular matrix.
  • Researchers discovered that magnesium activates the LFA-1 on CD8+ T cells, thereby increasing calcium influx, signal transduction, metabolic reprogramming, immunological interface, and cytotoxicity.
  • When LFA-1 detected high levels of magnesium, pathogen and tumor-specific T cell’s performance was improved, effectiveness of bi-specific T cell engaging antibodies was enhanced, and CAR T cell function was improved.
  • CAR T cells are a type of T cells that have been genetically modified to produce an artificial T cell receptor for use in immunological treatment.[3]
  • Low levels of magnesium in the blood were correlated with more rapid disease progression and lower survival rate in patients treated with CAR T cell and immune checkpoint antibody.
  • The findings highlight the relationship between co-stimulation and nutrient sensing, and direct to the magnesium-LFA-1 interaction as a therapeutically amenable biological system.

Sources:

Jonas Lötscher, Adrià-Arnau Martí i Líndez, Nicole Kirchhammer, Elisabetta Cribioli, Greta Giordano, Marcel P. Trefny, Markus Lenz, Sacha I. Rothschild, Paolo Strati, Marco Künzli, Claudia Lotter, Susanne H. Schenk, Philippe Dehio, Jordan Löliger, Ludivine Litzler, David Schreiner, Victoria Koch, Nicolas Page, Dahye Lee, Jasmin Grählert, Dmitry Kuzmin, Anne-Valérie Burgener, Doron Merkler, Miklos Pless, Maria L. Balmer, Walter Reith, Jörg Huwyler, Melita Irving, Carolyn G. King, Alfred Zippelius, Christoph Hess. Magnesium sensing via LFA-1 regulates CD8 T cell effector function. Cell, 2022; DOI: 10.1016/j.cell.2021.12.039

[1] https://ods.od.nih.gov/factsheets/Magnesium-Consumer

[2] https://www.sciencedirect.com/topics/medicine-and-dentistry/lymphocyte-function-associated-antigen-1

[3] https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell

Research Highlights: Superbug Methicillin-Resistant Staphylococcus aureus Existed in Hedgehogs Before the Introduction of Antibiotics


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shallow photo of hedgehog
Photo by Pixabay on Pexels.com

Superbug Methicillin-Resistant Staphylococcus aureus Existed in Hedgehogs Before the Introduction of Antibiotics

  • Human health significantly improved after antibiotics were discovered 80 years ago.
  • Antibiotic resistance in environmental bacteria is pretty well-known; however, resistance in human pathogenic bacteria is considered to be a modern occurrence that is caused by antibiotics.
  • Methicillin-resistant Staphylococcus aureus or MRSA is a well-known human pathogenic bacteria.
  • Researchers discovered that a particular lineages of MRSA existed in European hedgehogs before antibiotics were introduced.
  • Researchers also discovered that a fungus on these hedgehogs produces antibiotics that can eliminate susceptible bacteria but not MRSA.
  • The results suggest that the pre-antibiotic resistance emerged as an adaptation of S. aureus to the fungus-infected hedgehogs.
  • The discovery highlights One Health approach in which the health of human is closely related to the health of animals and the shared environment.
  • One Health approach in very important for our understanding and managing antibiotic resistance.


Sources:

Larsen, J., Raisen, C.L., Ba, X. et al. Emergence of methicillin resistance predates the clinical use of antibiotics. Nature (2022). https://doi.org/10.1038/s41586-021-04265-w

https://www.cdc.gov/onehealth/basics/index.html

Research Highlights: Mosquito and Malaria Parasite Are In A Mutualistic Relationship


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macro photo of a brown mosquito
Photo by Egor Kamelev on Pexels.com

Mosquito and Malaria Parasite Are In A Mutualistic Relationship

November 20, 2021

  • Anopheles is a genus of mosquito known to transmit the parasite Plasmodium that causes the disease malaria.
  • Malaria is one of the most harmful diseases in humans and can cause yellow skin, seizures, coma, and even death in severe cases.[1]
  • Malaria is transmitted when a mosquito becomes infected after biting an infected person, and then the infected mosquito bites a non-infected person.[2]
  • The evolutionary success of this transmission has been the long-term focus of debate and research study.
  • Researchers performed analysis to determine the effect of Plasmodium infection on the physiology of mosquito’s head, sensory appendages, and salivary glands.
  • Researchers compared the infected mosquitoes with the non-infected mosquitoes.
  • The result suggests that Plasmodium-infected mosquitoes had an increased sense of smell which can improve their ability to seek a host.
  • Additionally, Plasmodium-infected mosquitoes bear the hallmark of a younger, more reproduction-active insect.
  • The long-held thought that the Plasmodium causes disease in mosquitoes is now in question.
  • Data suggest that there are advantages for the mosquito that drives the conservation of its high transmission capability.

Related Video

Sources:

Carr, A.L., Rinker, D.C., Dong, Y. et al. Transcriptome profiles of Anopheles gambiae harboring natural low-level Plasmodium infection reveal adaptive advantages for the mosquito. Sci Rep 11, 22578 (2021). https://doi.org/10.1038/s41598-021-01842-x

[1] Caraballo H, King K (May 2014). “Emergency department management of mosquito-borne illness: malaria, dengue, and West Nile virus”. Emergency Medicine Practice. 16 (5): 1–23, quiz 23–4. PMID 25207355. Archived from the original on 2016-08-01.

[2] https://www.mayoclinic.org/diseases-conditions/malaria/multimedia/malaria-transmission-cycle/img-20006373

Research Highlights: Pathogenic Fungus On Infected Dead Female Flies Fools Male Flies To Mate


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By © Hans Hillewaert, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=6665971

Pathogenic Fungus On Infected Dead Female Flies Fools Male Flies To Mate

November 5, 2021

  • The recognition species concept is an idea that a species is characterized by a unique fertilization system that restricts gene-flow with other species.[3]
  • When males and females meet, mating competition and mating preferences may lead to low-quality decisions during mating.
  • Certain flowers exploit the willingness of an insect to mate by using sexual imitation to attract pollinator insects.
  • Some obligate pathogens can increase their chance for transmission when their host mate with the opposite conspecific member.
  • Also, many parasites and pathogens control the behavior of their host to ensure dispersal.
  • However, it is not normal for pathogens to rely on both behavioral manipulation and sexual imitation.
  • Researchers from the University of Copenhagen and the Swedish University of Agricultural Sciences show that the fungus, Entomophthora muscae, produces a chemical compound that alters the cuticular hydrocarbons of dead infected female house fly.[4]
  • E. muscae is a pathogenic fungus that causes disease in adult flies and has been identified as a potential biological agent for many years.
  • Cuticular hydrocarbons are primarily a moisture-saving agent present on the surface of an insect and are thought to play a role in insect communication.[2]
  • When the fungus alters the cuticular hydrocarbons of the dead female house fly, the male house flies respond to the compound produced by the fungi and are attracted into mating with the dead female.
  • This allows a higher probability of the fungus to infect the male flies due to its close proximity.
  • The research highlights the evolution of an extended phenotypic trait that exploit male flies’ tendency to mate and benefit the fungus by changing the behavior of uninfected male house flies.

Related Video

Sources:

Naundrup, A., Bohman, B., Kwadha, C., Jensen, A., Becher, P., De Fine Licht, H. (2021). A pathogenic fungus uses volatiles to entice male flies into fatal matings with infected female cadavers. bioRxiv. 0.1101/2021.10.21.465334. https://www.biorxiv.org/content/10.1101/2021.10.21.465334v1

[2] Drijfhout, Falko & Kather, R. & Martin, Stephen. (2013). The role of cuticular hydrocarbons in insects. Behavioral and Chemical Ecology. 91-114. https://www.researchgate.net/publication/286303349_The_role_of_cuticular_hydrocarbons_in_insects

[3] https://www.oxfordreference.com/view/10.1093/oi/authority.20110803100408187

[4] https://biocontrol.entomology.cornell.edu/pathogens/entomophagamuscae.php


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Research Highlights: Gut Bacteria Promote Therapy Resistant Prostate Cancer


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Image by Gerd Altmann from Pixabay

Gut Bacteria Promote Therapy Resistant Prostate Cancer

October 11, 2021

  • Androgens such as testosterone are important for male sexual and reproductive function.
  • Androgens play a role in the growth of prostate cancer cells.
  • Decreasing androgens by means of castration or hormone suppression is the current treatment for prostate cancer.
  • Castration refers to the process of removing the testicles in males.
  • The microbiota consist of microorganisms that inhabit a particular environment or location in or on the host.
  • Microbiota contains different types of organisms which includes symbiotic, commensal, and pathogenic microorganisms.
  • The role of the gut microbiota to the emergence of castration-resistance prostate cancer has not yet been addressed.
  • Researchers discovered that deprivation of androgen in mice and humans encourages the expansion of some commensal microbiota that helps to begin the castration resistance.
  • They found that when the body was deprived of androgens during the therapy, the gut microbiome could produce androgens from androgen precursors.
  • When the gut microbiota was removed by antibiotic therapy, the emergence of castration resistance was delayed even when mice are immunodeficient.
  • Fecal microbiota transplantation from castration-resistance prostate cancer mice and patients gave mice harboring prostate cancer resistant to castration.
  • In contrast, the growth of tumor was controlled by fecal microbiota transplantation from patients with hormone-sensitive prostate cancer.
  • Fecal microbiota transplantation, also known as a stool transplant, is the process of transferring fecal bacteria from a healthy individual into another individual.
  • The results suggest that the commensal gut bacteria contributes to endocrine resistance in castration-resistance prostate cancer by providing an alternative source of androgens.

Sources:

Pernigoni, N., Zagato, E., Calcinotto, A., Troiani, M., Mestre, R. P., Calì, B., Attanasio, G., Troisi, J., Minini, M., Mosole, S., Revandkar, A., Pasquini, E., Elia, A. R., Bossi, D., Rinaldi, A., Rescigno, P., Flohr, P., Hunt, J., Neeb, A., Buroni, L., … Alimonti, A. (2021). Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis. Science (New York, N.Y.), 374(6564), 216–224. https://doi.org/10.1126/science.abf8403

Research Highlights: Therapeutic Drug Accumulation in Gut Bacteria May Explain Individual Differences in Drug Response


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Dr. Microbe / iStock

Therapeutic Drug Accumulation in Gut Bacteria May Explain Individual Differences in Drug Response

September 12, 2021

  • The availability and efficacy of therapeutic drugs can be regulated by gut bacteria.
  • However, the systemic mapping of the drug-bacteria interactions has only started recently.
  • The primary underlying mechanism suggested is that microorganisms chemically transform drugs in the process called biotransformation.
  • Researchers investigated the reduction of 15 structurally diverse drugs by 25 representative strains of bacteria in the gut.
  • The study was led by researchers from the Medical Research Council Toxicology Unit at the University of Cambridge and the European Molecular Biology Laboratory in Heidelberg, Germany.
  • Researchers discovered 70 bacteria-drug interactions.
  • 29 of the 70 bacteria-drug interactions had not been reported.
  • More than 50 percent of the new interactions can be attributed to bioaccumulation.
  • In this context, bioaccumulation occurs when bacteria store the drug intracellularly without chemically modifying it.
  • Most of the time, bioaccumulation does not affect the growth of the bacteria.
  • Common drugs can accumulate in gut bacteria which can alter bacterial function and reduce drug effectiveness.
  • This interaction could help scientists better understand individual differences in drug responses.
  • Researchers studied the molecular basis of bioaccumulation of the widely used drug called duloxetine by using click chemistry, thermal proteome profiling, and metabolomics.
  • Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor antidepressant which is used to treat major depressive disorder in adults.[2]
  • Researchers found that duloxetine binds to several metabolic enzymes and affects the metabolite secretion of the respective bacteria.
  • The study used defined microbial community of accumulators and non-accumulators and found that duloxetine altered the composition of the community through metabolic cross-feeding.
  • Metabolic cross-feeding is defined as the interaction between bacterial strains in which molecules resulting from the metabolism of one strain are further metabolised by another strain.[3]
  • Researchers further validated their findings by using an animal model and found that bacterial bioaccumulation reduces the behavioral response of Caenorhabditis elegans to duloxetine.
  • In contrast, C. elegans with bacteria that did not accumulate duloxetine showed no behavioral changes.
  • C. elegans is a nematode worm commonly used to study gut bacteria.
  • The results suggest that bioaccumulation by bacteria in the gut may be a common mechanism that affects drug availability and bacterial metabolism.
  • Additionally, gut bacterial bioaccumulation can have an effect on microbiota composition, pharmacokinetics, side effects, and drug response, perhaps in an individual manner.

Sources:

Klünemann, M., Andrejev, S., Blasche, S., Mateus, A., Phapale, P., Devendran, S., Vappiani, J., Simon, B., Scott, T. A., Kafkia, E., Konstantinidis, D., Zirngibl, K., Mastrorilli, E., Banzhaf, M., Mackmull, M. T., Hövelmann, F., Nesme, L., Brochado, A. R., Maier, L., Bock, T., … Patil, K. R. (2021). Bioaccumulation of therapeutic drugs by human gut bacteria. Nature, 10.1038/s41586-021-03891-8. Advance online publication. https://doi.org/10.1038/s41586-021-03891-8

https://www.nature.com/articles/s41586-021-03891-8

[2] https://www.drugs.com/duloxetine.html

[3] https://www.frontiersin.org/articles/10.3389/fevo.2019.00153/full

Research Highlights: Cancer Cell Outcompetes T Cell in Methionine Consumption

T cells attacking cancer cells. Credit: Prasad Adusumilli

Original Article: https://doi.org/10.1038/s41586-020-2682-1

  • Abnormal epigenetic patterns is associated with effector T cell malfunction in tumors, but the cause of this correlation is unclear.
  • Methionine is an amino acid that is a component of most proteins, and it is an essential nutrient in the diet of vertebrates.
  • CD8+ T cell is a T lymphocyte that kills cancer cells.
  • The study show that tumor cells alter methionine metabolism in CD8+ T cells.
  • The alteration includes lowering the intracellular levels of methionine inside the cells.
  • The alteration also includes lowering the intracellular levels of methyl donor S-adenosylmethionine (SAM).
  • The result of these alteration is the loss of dimethylation at lysine 79 of histone H3 (H3K79me2).
  • Loss of H3K79me2 resulted in low expression of STAT5 and impaired T cell immunity.
  • STAT5 proteins are involved in cytosolic signalling and in mediating the expression of specific genes.
  • Mechanistically, tumor cells enthusiastically consumed methionine and outcompeted T cells.
  • Tumor cells compete with T cell for methionine by expressing high levels of the methionine transporter.
  • Genetic and biochemical inhibition of tumor methionine transporter restored H3K79me2 in T cells, as a result boosting spontaneous and checkpoint-induced tumor immunity.
  • In addition, methionine supplement improved the expression of H3K79me2 and STAT5 in T cells.
  • The improvement due to methionine supplementation went along with increased T cell immunity in tumor-bearing mice and patients with colon cancer.
  • Clinically, tumor methionine transporter has a negative correlation with T cell histone methylation and functional gene signatures.
  • The study identify a physical connection between methionine metabolism, histone patterns, and T cell immunity in the tumor micro-environment.
  • Cancer methionine consumption can be an immune evasion mechanism.
  • The study suggests that targeting cancer methionine signalling is a potential cancer therapy.

Source:

https://doi.org/10.1038/s41586-020-2682-1

https://languages.oup.com/google-dictionary-en/

https://doi.org/10.1016%2Fb978-0-12-817572-9.00007-0

https://doi.org/10.1093%2Femboj%2F18.17.4754

Keywords: cancer therapy, cancer cure, cancer treatment, cancer immunotherapy, how cancer cell affect t cell, t cell, immune system, immunity