Publications by authors named "Volker Brinkmann"

The antimicrobial activity of histones was discovered in the 1940s, but their mechanism of action is not fully known. Here we show that methicillin-resistant Staphylococcus aureus (MRSA) is susceptible to histone H1 (H1), even in the presence of divalent cations and serum. Through selective evolution and a genome-wide screen of a transposon library, as well as physiological and pharmacological experiments, we elucidated how H1 kills MRSA.

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Eosinophils control many aspects of the vertebrate innate immune response. They contribute to homeostasis, inflammatory conditions and defense against pathogens. With the varied functions of eosinophils, they have been found to play both protective and pathogenic roles in many diseases.

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Multiple peptide resistance factor (MprF) confers resistance to cationic antimicrobial peptides (AMPs) in several pathogens, thereby enabling evasion of the host immune response. The role of MprF in commensals remains, however, uncharacterized. To close this knowledge gap, we used a common gut commensal of animals, Lactiplantibacillus plantarum, and its natural host, the fruit fly Drosophila melanogaster, as an experimental model to investigate the role of MprF in commensal-host interactions.

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The gastroesophageal squamocolumnar junction (GE-SCJ) is a critical tissue interface between the esophagus and stomach, with significant relevance in the pathophysiology of gastrointestinal diseases. Despite this, the molecular mechanisms underlying GE-SCJ development remain unclear. Using single-cell transcriptomics, organoids, and spatial analysis, we examine the cellular heterogeneity and spatiotemporal dynamics of GE-SCJ development from embryonic to adult mice.

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Unlabelled: Activin A strongly influences immune responses; yet, few studies have examined its role in infectious diseases. We measured serum activin A levels in two independent tuberculosis (TB) patient cohorts and in patients with pneumonia and sarcoidosis. Serum activin A levels were increased in TB patients compared to healthy controls, including those with positive tuberculin skin tests, and paralleled severity of disease, assessed by X-ray scores.

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Resilience to short-term perturbations, like inflammation, is a fundamental feature of microbiota, yet the underlying mechanisms of microbiota resilience are incompletely understood. Here, we show that , a major commensal, stably colonizes the fruit fly gut during infection and is resistant to antimicrobial peptides (AMPs). By transposon screening, we identified mutants sensitive to AMPs.

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Mouse guanylate-binding proteins (mGBPs) are recruited to various invasive pathogens, thereby conferring cell-autonomous immunity against these pathogens. However, whether and how human GBPs (hGBPs) target (Mtb) and (Lm) remains unclear. Here, we describe hGBPs association with intracellular Mtb and Lm, which was dependent on the ability of bacteria to induce disruption of phagosomal membranes.

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Article Synopsis
  • - Maladjusted immune responses in COVID-19 can lead to severe issues like cytokine release syndrome and respiratory distress, signaling the need for effective treatments.
  • - Sphingosine-1-phosphate (S1P) and its receptors play a vital role in keeping blood vessel integrity and regulating immune cell movements, potentially improving outcomes in severe COVID-19 cases.
  • - The use of S1PR modulators like fingolimod and siponimod shows promise in reducing inflammation and could be beneficial for critically ill COVID-19 patients experiencing hyperinflammation.
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Neutrophils are critical to host defence, executing diverse strategies to perform their antimicrobial and regulatory functions. One tactic is the production of neutrophil extracellular traps (NETs). In response to certain stimuli, neutrophils decondense their lobulated nucleus and release chromatin into the extracellular space through a process called NETosis.

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  • - The research explores how coinfections with HPV16 and Chlamydia affect the cervical mucosa, utilizing patient-derived ectocervical organoids to mimic the cervical environment, which has previously limited the study of these interactions.
  • - Genetic manipulation of ectocervical stem cells created models that exhibit characteristics of precancerous lesions while still retaining their ability to develop into mature tissue, showing how HPV16 alters Chlamydia's behavior.
  • - The study reveals that Chlamydia not only disrupts HPV-induced cellular health mechanisms but also suggests that the unique interactions between these infections may contribute to an increased risk of cervical cancer.
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BCG - the only available vaccine against tuberculosis (TB) - was first given to babies 100 years ago in 1921. While it is effective against TB meningitis and disseminated TB, its efficacy against pulmonary TB is variable, notably in adults and adolescents. TB remains one of the world's leading health problems, with a higher prevalence among men.

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Mycofactocin is a new class of peptide-derived redox cofactors present in a selected group of bacteria including Mycobacterium tuberculosis. Mycofactocin biosynthesis requires at least six genes, including , encoding putative lactate dehydrogenase, which catalyzes the penultimate biosynthetic step. Cellular functions remained unknown until recent reports on the significance of mycofactocin in primary alcohol metabolism.

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  • The gastrointestinal epithelium maintains balance through the regeneration and differentiation of cells in glands and crypts, which is regulated by the Wnt/β-catenin pathway and various signaling signals.
  • Researchers created mucosoid cultures from human stomachs and tested different growth factors to identify how they contribute to the differentiation of specific cell types (foveolar, chief, and parietal cells).
  • Findings indicated that epidermal growth factor plays a crucial role in determining cell fate within gastric glands and may contribute to changes seen in precancerous conditions like atrophic gastritis, leading to a better understanding of gastric tissue signaling.
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Bacteriophages exert strong evolutionary pressure on their microbial hosts. In their lytic lifecycle, complete bacterial subpopulations are utilized as hosts for bacteriophage replication. However, during their lysogenic lifecycle, bacteriophages can integrate into the host chromosome and alter the host's genomic make-up, possibly resulting in evolutionary important adjustments.

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SARS-CoV-2, the agent that causes COVID-19, invades epithelial cells, including those of the respiratory and gastrointestinal mucosa, using angiotensin-converting enzyme-2 (ACE2) as a receptor. Subsequent inflammation can promote rapid virus clearance, but severe cases of COVID-19 are characterized by an inefficient immune response that fails to clear the infection. Using primary epithelial organoids from human colon, we explored how the central antiviral mediator IFN-γ, which is elevated in COVID-19, affects epithelial cell differentiation, ACE2 expression, and susceptibility to infection with SARS-CoV-2.

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Article Synopsis
  • The squamous and columnar epithelia are areas in the cervix that can develop cancer, often starting with a process called metaplasia, where one type of cell is replaced by another.
  • Researchers used advanced technology to study the different types of cells in these areas, discovering that they come from different types of stem cells that are controlled by opposite signals from surrounding tissue.
  • In experiments with mice, they found that changes in the tissue can lead to increased growth of certain stem cells, showing how the balance of cells at the transition zone is influenced by different signals in the tissue around them.
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Lactate dehydrogenase A (LDHA) mediates interconversion of pyruvate and lactate, and increased lactate turnover is exhibited by malignant and infected immune cells. Hypoxic lung granuloma in -infected animals present elevated levels of and lactate. Such alterations in the metabolic milieu could influence the outcome of host- interactions.

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  • Gliding motility and cell invasion are crucial for the transmission of Plasmodium parasites, relying on an acto-myosin motor under the plasma membrane.
  • The Myosin A-tail interacting protein (MTIP) is vital for linking the MyoA protein to gliding-associated proteins and for forming the motor assembly.
  • Research on Plasmodium berghei revealed that MTIP localizes to the front of motile ookinetes regardless of MyoA presence and that sporozoites have a specific MTIP distribution during movement, which is disrupted in mutant parasites with movement issues.
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Neutrophil extracellular traps (NETs) consist of decondensed chromatin fibers studded with granular and cytoplasmic proteins and peptides that are released by stimulated neutrophil granulocytes. If present in abundance (e.g.

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Neutrophils are essential innate immune cells that extrude chromatin in the form of neutrophil extracellular traps (NETs) when they die. This form of cell death has potent immunostimulatory activity. We show that heme-induced NETs are essential for malaria pathogenesis.

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Neutrophil granulocytes, also called polymorphonuclear leukocytes (PMN) due to their lobulated nucleus, are the most abundant type of leukocytes. They mature in the bone marrow and are released into the peripheral blood, where they circulate for about 6-8 h; however, in tissue, they can survive for days. By diapedesis through the endothelium, they leave the blood stream, enter tissues, and migrate towards the site of an infection following chemotactic gradients.

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  • The study focuses on a slow-growing, anaerobic bacterial species found on human skin and its unclear pathogenic potential.
  • Genetic analysis revealed significant misclassification of previously sequenced strains and identified two distinct genetic clades with differing features.
  • Findings suggest extensive genome decay and the bacterium's adaptation to its environment, indicating potential for tissue invasiveness and possible association with infections like prosthetic joint infections.
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Chronic infections of the fallopian tubes with Chlamydia trachomatis (Ctr) cause scarring and can lead to infertility. Here we use human fallopian tube organoids and genital Ctr serovars D, K and E for long-term in vitro analysis. The epithelial monolayer responds with active expulsion of the bacteria into the lumen and with compensatory cellular proliferation-demonstrating a role of epithelial homeostasis in the defense against this pathogen.

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