Biology subjects

Tetz, V.

Publications and source records attributed to Tetz, V..

12 recordsLinked to original sources

bioRxiv2025

Regulating white blood cell activity through the novel Universal Receptive System

The understanding of the mechanisms that control key features of immune cells in various disease contexts remains limited, and few techniques are available for manipulating immune cells. Thus, discovering novel strategies for regulating immune cells is essential for gaining insight into their roles in health and disease. In this study, we investigated the potential of the recently described Universal Receptive System to regulate human immune cell functions. This was achieved for the first time by specifically targeting newly discovered surface-bound DNA and RNA-based receptors on leukocytes and generating "Leukocyte-Tells." This approach upregulated numerous genes related to immune cell signaling, migration, endocytosis, and phagocytosis pathways. The antimicrobial and anticancer activities of Leukocyte-Tells exceeded the activity of control leukocytes in vitro. In some settings, such as in antibiofilm experiments, the Leukocyte-Tells showed up to 1,000,000-fold higher activities than control leukocytes. Our findings reveal, for the first time, that the Universal Receptive System can orchestrate fundamental properties of immune cells, including enhanced antimicrobial and anti-tumor activities. This novel approach offers a new avenue for understanding the biology and regulation of white blood cells.

immunology↗

bioRxiv2024

The Universal Receptive System acts as a novel regulator in the production of antimicrobial and anticancer bioactive compounds by white blood cells

Despite recent advances, the regulation of anticancer and antimicrobial bioactive compound (AABC) production by leukocytes remains poorly understood. Here, we demonstrate that inactivation of the DNA- and RNA-based Teazeled receptors of the Universal Receptive System in human leukocytes generated so called "Leukocyte-Tells," which showed enhanced AABC production. Comprehensive analysis of the AABCs produced by Leukocyte-Tells based on LC/MS identified 707 unique or differentially produced peptide or non-peptide metabolites. Functional testing demonstrated that many of these metabolites exhibited increased antibacterial, antifungal, and anticancer activities. The AABCs produced by the Leukocyte-Tells were effective against different multidrug-resistant clinical isolates of fungi and gram-positive and gram-negative bacteria (including their biofilms), as well as various cancer cell lines, with >100,000-fold activity than AABCs derived from control leukocytes. Notably, the AABCs produced by the Leukocyte-Tells exhibited greater stability under adverse environmental conditions. Our findings highlight the important role of the Universal Receptive System in regulating AABC production through a process named here as cell genome memory management, offering new insights into immune functions and suggesting potential therapeutic applications. SummaryThe Universal Receptive System acts as a novel regulator of biosynthetic activity in leukocytes. Modulating the leukocyte Universal Receptive System by inactivating Teazeled receptors triggers the production of new compounds not observed in naive cells. We refer to these TezR-modified cells as "Leukocyte-Tells." Leukocytes produce unique metabolites with strong anticancer and antimicrobial activities. Reproducibility in generating leukocytes from the blood of different donors suggests that the observed alterations in cell activity were preprogrammed.

molecular biology↗

bioRxiv2024

Universal Receptive System as a novel regulator of transcriptomic activity of Staphylococcus aureus

Our previous studies revealed the existence of a Universal Receptive System that regulates interactions between cells and their environment. This system is composed of DNA- and RNA-based Teazeled receptors (TezRs) found on the surface of prokaryotic and eukaryotic cells, as well as integrases and recombinases.. In the current study, we aimed to provide further insight into the regulatory role of TezR and its loss in Staphylococcus aureus gene transcription. To this end, transcriptomic analysis of S. aureus MSSA VT209 was performed following the destruction of TezRs. Bacterial RNA samples were extracted from nuclease-treated and untreated S. aureus MSSA VT209. After destruction of the DNA-based-, RNA-, or combined DNA- and RNA-based TezRs of S. aureus, 103, 150, and 93 genes were significantly differently expressed, respectively. The analysis revealed differential clustering of gene expression following the loss of different TezRs, highlighting individual cellular responses following the loss of DNA- and RNA-based TezRs. KEGG pathway gene enrichment analysis revealed that the most upregulated pathways following TezR inactivation included those related to energy metabolism, cell wall metabolism, and secretion systems. Some of the genetic pathways were related to the inhibition of biofilm formation and increased antibiotic resistance, and we confirmed this at the phenotypic level using in vitro studies. The results of this study add another line of evidence that the Universal Receptive System plays an important role in cell regulation, including cell responses to the environmental factors of clinically important pathogens, and that nucleic acid-based TezRs are functionally active parts of the extrabiome.

microbiology↗

bioRxiv2024

Previously unknown regulatory role of extracellular RNA on bacterial directional migration

Bacterial directional migration plays a significant role in bacterial adaptation. However, the regulation of this process, particularly in young biofilms, remains unclear. Here, we demonstrated the critical role of extracellular RNA as part of the Universal Receptive System in bacterial directional migration using a multidisciplinary approach, including bacterial culture, biochemistry, and genetics. We found that the destruction or inactivation of extracellular RNA with RNase or RNA-specific antibodies in the presence of the chemoattractant triggered the formation of bacterial "runner cells>> in what we call a "panic state" capable of directional migration. These cells quickly migrated even on the surface of 1.5% agar and formed evolved colonies that were transcriptionally and biochemically different from the ancestral cells. We have also shown that cell-free DNA from blood plasma can act as a potent bacterial chemoattractant. Our data revealed a previously unknown role of bacterial extracellular RNA in the regulation of bacterial migration and have shown that its destruction or inhibition triggered the directional migration of developing and mature biofilms towards the chemoattractant.

microbiology↗

bioRxiv2023

Antifungal activity of the novel compound M451 against phytopathogens

Phytopathogenic fungi are the dominant causal agents of plant diseases. Currently available fungicides have significant disadvantages, being insufficiently effective owing to both intrinsic tolerance and the spread of antibiotic resistance accumulating in plant tissues, posing a global threat to public health. Finding a new broad-spectrum fungicide is a challenge for plant protection. We studied the potency of a novel antimicrobial agent, M451, against different phytopathogenic fungi of the phyla Ascomycota, Oomycota, and Basidiomycota. M451 exhibited significant antifungal activity with EC50 values ranging from 34 to 145 {micro}g/mL. Analysis of the minimal fungicidal concentration and conidial destruction assay revealed that M451 possesses the highest activity compared with different polyene, azole, and phenylpyrrole antifungals against Fusarium oxysporum. Time-kill analysis revealed that M451 was the only antifungal agent tested that exhibited antifungal activity within 5 min of exposure. Spore production and germination were also significantly inhibited by M451 treatment. Based on the broad spectrum of antifungal effects across different plant pathogens, M451 could be a new chemical fungicide for plant disease management.

microbiology↗

bioRxiv2021

Novel prokaryotic sensing and regulatory system employing previously unknown nucleic acids-based receptors

The present study describes a previously unknown universal signaling and regulatory system, which we named TRB receptor system. This system is responsible for sensing, remembering, and regulating cell responses to various chemical, physical or biological stimuli. It controls cell survival, variability, reproduction, adaptation, genome changes, and gene transfer. Importantly, the TRB-receptor system is responsible for the formation and maintenance of cell memory, as well the ability to "forget" preceding events. The system is composed of DNA- and RNA-based receptors located outside the membrane named "TezRs", as well as reverse transcriptases and integrases. The sensory and regulatory functions of TezRs enable the TRB-receptor system to control all major aspects of bacterial behavior, such as growth, biofilm formation and dispersal, utilization of nutrients including xenobiotics, virulence, chemo- and magnetoreception, response to external factors (e.g., temperature, UV, light and gas content), mutation events, phage-host interaction and recombination activity. Additionally, it supervises the function of other receptor-mediated signaling pathways. Transcriptome analysis revealed that the loss of different TezRs instigates significant alterations in gene expression. HIGHLIGHTSThe TRB-receptor system regulates bacterial sensing and response to various stimuli. The TRB-receptor system is responsible for maintenance and loss of cell memory. The TRB-receptor system comprises DNA- and RNA-based "TezRs" receptors. The TRB-receptor system relies on reverse transcriptases and recombinases. The TRB-receptor system oversees other receptor-mediated signaling pathways. TezRs are implicated in cell mutation and recombination events.

microbiology↗

bioRxiv2019

Bacterial DNA promotes Tau aggregation

A hallmark feature of Alzheimers disease (AD) and other tauopathies is the misfolding, aggregation and cerebral accumulation of tau deposits. Compelling evidence indicates that misfolded tau aggregates are neurotoxic, producing synaptic loss and neuronal damage. Misfolded tau aggregates are able to spread the pathology from cell-to-cell by a prion like seeding mechanism. The factors implicated in the initiation and progression of tau misfolding and aggregation are largely unclear. In this study, we evaluated the effect of DNA extracted from diverse prokaryotic and eukaryotic cells in tau misfolding and aggregation. Our results show that DNA from various, unrelated gram-positive and gram-negative bacteria results in a more pronounced tau misfolding compared to eukaryotic DNA. Interestingly, a higher effect in promoting tau aggregation was observed for DNA extracted from certain bacterial species previously detected in the brain, CSF or oral cavity of patients with AD. Our findings indicate that microbial DNA may play a previously overlooked role in the propagation of tau protein misfolding and AD pathogenesis, providing a new conceptual framework that positions the compromised blood-brain and intestinal barriers as important sources of microbial DNA in the CNS, opening novel opportunities for therapeutic interventions.

microbiology↗

bioRxiv2019

Bacterial DNA induces the formation of heat-resistant disease-associated \"Tetz-proteins\" in human plasma

Our study demonstrated for the first time that bacterial extracellular DNA (eDNA) can change the thermal behaviour of specific human plasma proteins, leading to an elevation of the heat-resistant protein fraction, as well as to de novo acquisition of heat-resistance. In fact, the majority of these proteins were not known to be heat-resistant and nor do they possess any prion-like domain. Proteins found to become heat-resistant following DNA exposure were named \"Tetz-proteins\".\n\nInterestingly, plasma proteins that become heat-resistant following treatment with bacterial eDNA are known to be associated with cancer progression. Therefore, we analysed the heat-resistant proteome in the plasma of healthy subjects and in patients with pancreatic cancer and found that exposure to bacterial eDNA made the proteome of healthy subjects more similar to that of cancer patients. These findings open a discussion on the possible novel role of eDNA in disease development following its interaction with specific proteins, including those involved in multifactorial diseases such as cancer.

microbiology↗

bioRxiv2019

Evaluation of the novel culture-based FAST-T system allowing selection of optimal antibiotics for critically ill patients within 4 h (for other than bloodstream infectious).

Rapid diagnostic tests are needed to improve patient care, particularly in immunocompromised hosts. Here, we describe the validation of a new phenotypic culture-based FAST-T method for rapid selection of antibiotics in vitro using specimens with mono-and polybacterial infections. FAST-T approach, which can be applied to any type of non-blood tissue, does not require isolation of pure bacterial cultures. FAST-T-selected antibiotics are those that can completely eliminate mixed bacterial infections in specimens. The method uses a novel FASM-T medium that allows more rapid bacterial growth of gram-positive and gram-negative monoisolates compared with that achieved with conventional laboratory media. The application of the FAST-T method in 122 bacterial species demonstrated overall sensitivity, specificity, positive predictive value, and negative predictive value of 99.6%, 98.1%, 98.5%, and 99.4%, respectively, already after 4 h. The overall category agreement with the outcome of standard testing was 98.9% with very major errors and major errors being detected in 1.2% and 0.6% of cases.\n\nThe use of FASM-T medium in 20 clinical polymicrobial samples allowed culturing a more diverse set of bacteria, including fastidious species, compared with that achieved with the standard laboratory diagnostic and enabled, already within 4 h, accurate selection of the antibiotics that completely eliminated all cultivatable bacteria from clinical samples. In conclusion, FAST-T system may be a valuable tool in improving phenotypic-based antibiotic selection, enabling targeted empirical therapy and accurate antibiotic replacement, which is especially important in high-risk patients.

microbiology↗

bioRxiv2018

Type 1 Diabetes: an Association Between Autoimmunity the Dynamics of Gut Amyloid-producing E. coli and Their Phages

The etiopathogenesis of type 1 diabetes (T1D), a common autoimmune disorder, is not completely understood. Recent studies suggested the gut microbiome plays a role in T1D. We have used public longitudinal microbiome data from T1D patients to analyze amyloid-producing bacterial composition and found a significant association between initially high amyloid-producing Escherichia coli abundance, subsequent E. coli depletion prior to seroconversion, and T1D development. In children who presented seroconversion or developed T1D, we observed an increase in the E. coli phage/E. coli ratio prior to E. coli depletion, suggesting that the decrease in E. coli was due to prophage activation. Evaluation of the role of phages in amyloid release from E. coli biofilms in vitro suggested an indirect role of the bacterial phages in the modulation of host immunity.\n\nThis study for the first time suggests that amyloid-producing E. coli, their phages, and bacteria-derived amyloid might be involved in pro-diabetic pathway activation in children at risk for T1D.

microbiology↗

bioRxiv2018

In vitro activity of a novel antifungal compound, MYC-053, against clinically significant antifungal-resistant strains of Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis spp.

An urgent need exists for new antifungal compounds to treat fungal infections in immunocompromised patients. The aim of the current study was to investigate the potency of a novel antifungal compound, MYC-053, against the emerging yeast and yeast-like pathogens Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis spp. MYC-053 was equally effective against the susceptible control strains, clinical isolates, and resistant strains, with the minimum inhibitory concentrations (MIC) of 0.125-4.0 g/mL. Notably, unlike other antifungal compounds, MYC-053 was effective against Pneumocystis isolates. MYC-053 was highly effective against preformed 48-h-old yeast biofilms, with the minimal biofilm eradication concentrations equal to 1-4 times MIC. The compound was not cytotoxic against L2 and A549 cell lines at concentrations over 100 g/ml. Further, it possessed no apparent hemolytic activity up to 1000 g/ml (the highest concentration tested). Overall, these data indicated that MYC-053 has a broad therapeutic window and may be developed into a promising antifungal agent for the treatment and prevention of invasive fungal infections caused by yeasts and yeast-like fungi in neutropenic patients.

microbiology↗

bioRxiv2018

Parkinsons disease and bacteriophages as its overlooked contributors

Recent studies suggest that alterations in the gut phagobiota may contribute to pathophysiological processes in mammals; however, the association of bacteriophage community structure with Parkinsons disease (PD) has not been yet characterized. Towards this end, we used a published dataset to analyse bacteriophage composition and determine the phage/bacteria ratio in faecal samples from drug-naive PD patients and healthy participants. Our analyses revealed significant alterations in the representation of certain bacteriophages in the phagobiota of PD patients. We identified shifts of the phage/bacteria ratio in lactic acid bacteria known to produce dopamine and regulate intestinal permeability, which are major factors implicated in PD pathogenesis. Furthermore, we observed the depletion of Lactococcus spp. in the PD group, which was most likely due to the increase of lytic c2-like and 936-like lactococcal phages frequently present in dairy products. Our findings add bacteriophages to the list of possible factors associated with the development of PD, suggesting that gut phagobiota composition may serve as a diagnostic tool as well as a target for therapeutic intervention, which should be confirmed in further studies. Our results open a discussion on the role of environmental phages and phagobiota composition in health and disease.

microbiology↗