Search Results (3,017)

Background: Glioblastoma (GBM) is a highly aggressive, invasive, and growth factor-independent grade IV glioma. Survival following the diagnosis is generally poor, with a median survival of approximately 15 months, and it is considered the most aggressive and lethal central nervous system tumor. Conventional treatments based on surgery, chemotherapy, and radiation therapy only delay progression, and death is inevitable. Malignant glioma cells are resistant to traditional therapies, potentially due to a subpopulation of glioma stem cells that are invasive and capable of rapid regrowth. Methods: This is a literature review. The systematic retrieval of information was performed on PubMed, Embase, and Google Scholar. Specified keywords were used in PubMed and the articles retrieved were published in peer-reviewed scientific journals and were associated with brain GBM cancer and the sodium iodide symporter (NIS). Additionally, the words ‘radionuclide therapy OR mesenchyma, OR radioiodine OR iodine-131 OR molecular imaging OR gene therapy OR translational imaging OR targeted OR theranostic OR symporter OR virus OR solid tumor OR combined therapy OR pituitary OR plasmid AND glioblastoma OR GBM OR GB OR glioma’ were also used in the appropriate literature databases of PubMed and Google Scholar. A total of 68,244 articles were found in this search on Mesenchymal Stem Cell Sodium Iodide Symporter and GBM. These articles were found till 2024. To study recent advances, a filter was added to include articles only from 2014 to 2024, duplicates were removed, and articles not related to the title were excluded. These came out to be 78 articles. From these, nine were not retrieved and only seven were selected after the removal of keyword mismatched articles. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. Results: As a result of their natural capacity to identify malignancies, MSCs are employed as tumor therapy vehicles. Because MSCs may be transplanted using several methods, they have been proposed as the ideal vehicles for NIS gene transfer. MSCs have been used as a delivery vector for anticancer drugs in many tumor models due to their capacity to move precisely to malignancies. Also, by directly injecting radiolabeled MSCs into malignant tumors, a therapeutic dosage of beta radiation may be deposited, with the added benefit that the tumor would only localize and not spread to the surrounding healthy tissues. Conclusion: The non-invasive imaging-based detection of glioma stem cells presents an alternate means to monitor the tumor and diagnose and evaluate recurrence. The sodium iodide symporter gene is a specific gene in a variety of human thyroid diseases that functions to move iodine into the cell. In recent years, an increasing number of studies related to the sodium iodide symporter gene have been reported in a variety of tumors and as therapeutic vectors for imaging and therapy. Gene therapy and nuclear medicine therapy for GBM provide a new direction. In all the preclinical studies reviewed, image-guided cell therapy led to greater survival benefits and, therefore, has the potential to be translated into techniques in glioblastoma treatment trials. Full article

Bacteria have defense systems against the penetration of foreign DNA (phages and plasmids). Some defense systems protect bacteria from phage penetration into the cell, while others block phage replication. Antiphage defense systems are often located next to already known defense systems (RM system, CRISP-Cas system, and others). In this work, the genetic sequence flanking the restriction–modification system of Microbacterium sp. strain Gd 4-13 was analyzed. The genes of the endonuclease HNH, hypothetical proteins, recombinase, and helicase/ATPase have been identified. Their combination and some analogy with the DISARM, BREX, and Druantia systems allow us to hypothesize that, next to the MspGI restriction–modification system, there is another defense system, and together they create an island of antiphage defense in the bacteria in vivo. Full article

Contaminations with cephalosporin-resistant Escherichia coli across the food chain may pose a significant threat to public health because those antimicrobials are critically important in human medicine. The impact of the presented data is especially significant concerning Poland’s role as one of the leading food producers in the EU. This work aimed to characterize the genomic contents of cephalosporin-resistant Escherichia coli (n = 36) isolated from retail meat to expand the official AMR monitoring reported by EFSA. The ESBL mechanism was predominant (via bla_CTX-M-1 and bla_SHV-12), with the AmpC-type represented by the bla_CMY-2 variant. The strains harbored multiple resistance genes, mainly conferring resistance to aminoglycosides, sulfonamides, trimethoprim, tetracyclines. In some isolates, virulence factors—including intimin (eae) and its receptor (tir) were detected, indicating significant pathogenic potential. Resistance genes showed a link with IncI1 and IncB/O/K/Z plasmids. Cephalosporinases were particularly linked to ISEc9/ISEc1 (bla_CTX-M-1 and bla_CMY-2). The association of virulence with mobile elements was less common—mostly with IncF plasmids. The analysis of E. coli isolated from retail meat indicates accumulation of ARGs and their association with various mobile genetic elements, thus increasing the potential for the transmission of resistance across the food chain. Full article

Combinatorial antiretroviral therapy (cART) has transformed HIV infection from a death sentence to a controllable chronic disease, but cannot eliminate the virus. Latent HIV-1 reservoirs are the major obstacles to cure HIV-1 infection. Previously, we engineered exosomal Tat (Exo-Tat) to reactivate latent HIV-1 from the reservoir of resting CD4+ T cells. Here, we present an HIV-1 eradication platform, which uses our previously described Exo-Tat to activate latent virus from resting CD4+ T cells guided by the specific binding domain of CD4 in interleukin 16 (IL16), attached to the N-terminus of exosome surface protein lysosome-associated membrane protein 2 variant B (Lamp2B). Cells with HIV-1 surface protein gp120 expressed on the cell membranes are then targeted for immune cytolysis by a BiTE molecule CD4-αCD3, which colocalizes the gp120 surface protein of HIV-1 and the CD3 of cytotoxic T lymphocytes. Using primary blood cells obtained from antiretroviral treated individuals, we find that this combined approach led to a significant reduction in replication-competent HIV-1 in infected CD4+ T cells in a clonal in vitro cell system. Furthermore, adeno-associated virus serotype DJ (AAV-DJ) was used to deliver Exo-Tat, IL16lamp2b and CD4-αCD3 genes by constructing them in one AAV-DJ vector (the plasmid was named pEliminator). The coculture of T cells from HIV-1 patients with Huh-7 cells infected with AAV-Eliminator viruses led to the clearance of HIV-1 reservoir cells in the in vitro experiment, which could have implications for reducing the viral reservoir in vivo, indicating that Eliminator AAV viruses have the potential to be developed into therapeutic biologics to cure HIV-1 infection. Full article

Microorganisms harbor catabolic plasmids to tackle refractory organic pollutants, which is crucial for bioremediation and ecosystem health. Understanding the impacts of plasmids on hosts provides insights into the behavior and adaptation of degrading bacteria in the environment. Here, we examined alterations in the physiological properties and gene expression profiles of Rhodococcus sp. strain p52 after losing two conjugative dioxin-catabolic megaplasmids (pDF01 and pDF02). The growth of strain p52 accelerated after pDF01 loss, while it decelerated after pDF02 loss. During dibenzofuran degradation, the expression levels of dibenzofuran catabolic genes on pDF01 were higher compared to those on pDF02; accordingly, pDF01 loss markedly slowed dibenzofuran degradation. It was suggested that pDF01 is more beneficial to strain p52 under dibenzofuran exposure. Moreover, plasmid loss decreased biofilm formation, especially after pDF02 loss. Transcriptome profiling revealed different pathways enriched in upregulated and downregulated genes after pDF01 and pDF02 loss, indicating different adaptation mechanisms. Based on the transcriptional activity variation, pDF01 played roles in transcription and anabolic processes, while pDF02 profoundly influenced energy production and cellular defense. This study enhances our knowledge of the impacts of degradative plasmids on native hosts and the adaptation mechanisms of hosts, contributing to the application of plasmid-mediated bioremediation in contaminated environments. Full article

Recombination hotspot-activating DNA sites (e.g., M26, CCAAT, Oligo-C) and their binding proteins (e.g., Atf1-Pcr1 heterodimer; Php2-Php3-Php5 complex, Rst2, Prdm9) regulate the distribution of Spo11 (Rec12)-initiated meiotic recombination. We sought to create 14 different candidate regulatory DNA sites via bp substitutions in the ade6 gene of Schizosaccharomyces pombe. We used a fission yeast-optimized CRISPR-Cas9 system (SpEDIT) and 196 bp-long dsDNA templates with centrally located bp substitutions designed to ablate the genomic PAM site, create specific 15 bp-long DNA sequences, and introduce a stop codon. After co-transformation with a plasmid that encoded both the guide RNA and Cas9 enzyme, about one-third of colonies had a phenotype diagnostic for DNA sequence changes at ade6. PCR diagnostics and DNA sequencing revealed a diverse collection of alterations at the target locus, including: (A) complete or (B) partial template-directed substitutions; (C) non-homologous end joinings; (D) duplications; (E) bp mutations, and (F) insertions of ectopic DNA. We concluded that SpEDIT can be used successfully to generate a diverse collection of DNA sequence elements within a reporter gene of interest. However, its utility is complicated by low efficiency, incomplete template-directed repair events, and undesired alterations to the target locus. Full article

Salmonella species are causal pathogens instrumental in human food-borne diseases. The pandemic survey related to multidrug resistant (MDR) Salmonella genomics enables the prevention and control of their dissemination. Currently, serotype Mbandaka is notorious as a multiple host-adapted non-typhoid Salmonella. However, its epidemic and MDR properties are still obscure, especially its genetic determinants accounting for virulence and MD resistance. Here, we aim to characterize the genetic features of a strain SMEH pertaining to Salmonella Mbandaka (S. Mbandaka), isolated from the patient’s hydropericardium, using cell infections, a mouse model, antibiotic susceptibility test and comparative genomics. The antibiotic susceptibility testing showed that it could tolerate four antibiotics, including chloramphenicol, tetracycline, fisiopen and doxycycline by Kirby–Bauer (K-B) testing interpreted according to the Clinical and Laboratory Standards Institute (CLSI). Both the reproducibility in RAW 264.7 macrophages and invasion ability to infect HeLa cells with strain SMEH were higher than those of S. Typhimurium strain 14028S. In contrast, its attenuated virulence was determined in the survival assay using a mouse model. As a result, the candidate genetic determinants responsible for antimicrobial resistance, colonization/adaptability and their transferability were comparatively investigated, such as bacterial secretion systems and pathogenicity islands (SPI-1, SPI-2 and SPI-6). Moreover, collective efforts were made to reveal a potential role of the plasmid architectures in S. Mbandaka as the genetic reservoir to transfer or accommodate drug-resistance genes. Our findings highlight the essentiality of antibiotic resistance and risk assessment in S. Mbandaka. In addition, genomic surveillance is an efficient method to detect pathogens and monitor drug resistance. The genetic determinants accounting for virulence and antimicrobial resistance underscore the increasing clinical challenge of emerging MDR Mbandaka isolates, and provide insights into their prevention and treatment. Full article

Rats are particularly important from an epidemiological point of view, because they are regarded as reservoirs for diverse zoonotic pathogens including enteric bacteria. This study is the first to report the emergence of Salmonella serovar Ohio in brown rats (Rattus norvegicus) and food-producing animals in Hungary. We first reveal the genomic diversity of the strains and their phylogenomic relationships in the context of the international collection of S. Ohio genomes. This pathogen was detected in 4.3% (4/92) of rats, captured from multiple sites in Hungary. A whole-genome-based genotype comparison of S. Ohio, Infantis, Enteritidis, and Typhimurium strains showed that 76.4% (117/153) of the virulence and antimicrobial resistance genes were conserved among these serovars, and none of the genes were specific to S. Ohio. All S. Ohio strains lacked virulence and resistance plasmids. The cgMLST phylogenomic comparison highlighted a close genetic relationship between rat and poultry strains of S. Ohio from Hungary. These strains clustered together with the international S. Ohio genomes from aquatic environments. Overall, this study contributes to our understanding of the epidemiology of Salmonella spp. in brown rats and highlights the importance of monitoring to minimize the public health risk of rodent populations. However, further research is needed to understand the route of infection and evolution of this serovar. Full article

Herein, we investigated the toxicity and membrane-permeabilizing capabilities of Lpt and Lpt-like peptides, belonging to type I toxin–antitoxin systems carried by plasmid DNA of Lacticaseibacillus strains. These 29 amino acid peptides are predicted to form α-helical structures with a conserved central hydrophobic sequence and differently charged hydrophilic termini. Like Lpt, the expression of Lpt-like in E. coli induced growth arrest, nucleoid condensation, and cell membrane damage, suggesting membrane interaction as the mode of action. The membrane permeabilization activity of both peptides was evaluated by using liposome leakage assays, dynamic light scattering, and CD spectroscopy. Lpt and Lpt-like showed liposome leakage activity, which did not lead to liposome disruption but depended on peptide concentration. Lpt was generally more effective than Lpt-like, probably due to different physical chemical properties. Leakage was significantly reduced in larger liposomes and increased with negatively charged PCPS liposomes, indicating that electrostatic interactions and membrane curvature influence peptide activity. Contrary to most membrane-active peptides, Lpt an Lpt-like progressively lost their α-helical structure upon interaction with liposomes. Our data are inconsistent with the formation of membrane-spanning peptide pores but support a mechanism relying on the transient failure of the membrane permeability barrier possibly through the formation of “lipid pores”. Full article

Antimicrobial resistance (AMR) is a significant global health threat, with multidrug-resistant (MDR) bacterial clones becoming a major concern. Polymyxins, especially colistin, have reemerged as last-resort treatments for MDR Gram-negative infections. However, colistin use in livestock has spread mobile colistin resistance (mcr) genes, notably mcr-1, impacting human health. In consequence, its livestock use was banned in 2017, originating a natural experiment to study bacterial adaptation. The aim of this work was to analyse the changes in the mcr-1 genetic background after colistin restriction across the world. This study analyses 3163 Escherichia coli genomes with the mcr-1 gene from human and livestock hosts, mainly from Asia (n = 2621) and Europe (n = 359). Genetic characterisation identifies IncI2 (40.4%), IncX4 (26.7%), and multidrug-resistant IncHI2 (18.8%) as the most common plasmids carrying mcr-1. There were differences in plasmids between continents, with IncX4 (56.6%) being the most common in Europe, while IncI2 (44.8%) was predominant in Asia. Promoter variants related to reduced fitness costs and ISApl1 showed a distinct pattern of association that appears to be associated with adaptation to colistin restriction, which differed between continents. Thus, after the colistin ban, Europe saw a shift to specialised mcr-1 plasmids as IncX4, while ISApl1 decreased in Asia due to changes in the prevalence of the distinct promoter variants. These analyses illustrate the evolution of mcr-1 adaptation following colistin use restrictions and the need for region-specific strategies against AMR following colistin restrictions. Full article

Given the lack of genetic characterization data for multidrug-resistant (MDR) Salmonella in South Korean poultry, we analyzed 53 MDR Salmonella strains from 1232 poultry meat samples (723 chicken, 509 duck) using whole-genome sequencing. Five serotypes were identified: S. Infantis (30/53, 56.6%), S. Enteritidis (11/53, 20.8%), S. Virchow (9/53, 17.0%), S. Agona (2/53, 3.8%), and S. Indiana (1/53, 1.9%). Sequence types (STs) included ST32, ST11, ST16, ST13, and ST17, with three major clusters, each having two subclusters. Eight core genome sequence types (cgSTs) were identified: 225993, 2268, 58360, 150996, 232041, 96964, 117577, and 267045. Salmonella Infantis and S. Enteritidis had two (117577, 267045) and three (225993, 2268, 58360) cgSTs, respectively, whereas S. Virchow showed allelic differences in identical cgSTs. The S. Enteritidis subcluster was classified as chicken or duck. Twenty-eight antimicrobial resistance genes (ARGs), 10 plasmid replicons, 11 Salmonella pathogenicity islands (SPIs), and 230 virulence genes were identified, showing distinct profiles by cluster and subcluster. Salmonella Infantis, the primary MDR Salmonella, carried the IncFIB (pN55391) plasmid, 10–11 ARGs, nine SPIs, and approximately 163 virulence genes. Three major MDR Salmonella serotypes (S. Infantis, S. Enteritidis, and S. Virchow) had specific genetic profiles that can inform epidemiological surveillance. Full article

To gain deeper insights into the genomic characteristics of Limosilactobacillus reuteri (L. reuteri) YLR001 and uncover its probiotic properties, in the current study, a comprehensive analysis of its whole genome was conducted, explicitly exploring the genetic variations associated with different host organisms. The genome of YLR001 consisted of a circular 2,242,943 bp chromosome with a GC content of 38.84%, along with three circular plasmids (24,864, 38, 926, and 132,625 bp). Among the 2183 protein-coding sequences (CDSs), the specific genes associated with genetic adaptation and stress resistance were identified. We predicted the function of COG protein genes and analyzed the KEGG pathways. Comparative genome analysis revealed that the pan-genome contained 5207 gene families, including 475 core gene families and 941 strain-specific genes. Phylogenetic analysis revealed distinct host specificity among 20 strains of L. reuteri, highlighting substantial genetic diversity across different hosts. This study enhanced our comprehension of the genetic diversity of L. reuteri YLR001, demonstrated its potential probiotic characteristics, and established more solid groundwork for future applications. Full article

Staphylococcus aureus stands out as one of the most virulent pathogens in the genus Staphylococcus. This characteristic is due to its ability to produce a wide variety of staphylococcal enterotoxins (SEs) and exotoxins, which in turn can cause staphylococcal food poisoning (SFP), clinical syndromes such as skin infections, inflammation, pneumonia, and sepsis, in addition to being associated with the development of inflammation in the mammary glands of dairy cattle, which results in chronic mastitis and cell necrosis. SEs are small globular proteins that combine superantigenic and emetic activities; they are resistant to heat, low temperatures, and proteolytic enzymes and are tolerant to a wide pH range. More than 24 SE genes have been well described (SEA-SEE, SEG, SEH, SEI, SEJ, SElK, SElL, SElM, SElN, SElO, SElP, SElQ, SElR, SElS, SElT, SElU, SElV, SElW, SElX, SElY, and SElZ), being a part of different SFP outbreaks, clinical cases, and isolated animal strains. In recent years, new genes (sel26, sel27, sel28, sel31, sel32, and sel33) from SEs have been described, as well as two variants (seh-2p and ses-3p) resulting in a total of thirty-three genes from Ses, including the nine variants that are still in the process of genetic and molecular structure evaluation. SEs are encoded by genes that are located in mobile genetic elements, such as plasmids, prophages, pathogenicity islands, and the enterotoxin gene cluster (egc), and housed in the genomic island of S. aureus. Both classical SEs and SE-like toxins (SEls) share phylogenetic relationships, structure, function, and sequence homology, which are characteristics for the production of new SEs through recombination processes. Due to the epidemiological importance of SEs, their rapid assessment and detection have been crucial for food security and public health; for this reason, different methods of identification of SEs have been developed, such as liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS), molecular methods, and whole-genome sequencing; providing the diagnosis of SEs and a better understanding of the occurrence, spread, and eradication of SEs. This review provides scientific information on the enterotoxins produced by S. aureus, such as structural characteristics, genetic organization, regulatory mechanisms, superantigen activity, mechanisms of action used by SEs at the time of interaction with the immune system, methods of detection of SEs, and recent biocontrol techniques used in food. Full article

Compounds derived from natural sources pave the way for novel drug development. Cyanobacteria is an ubiquitous phylum found in various habitats. The fitness of those microorganisms, within different biotopes, is partially dependent on secondary metabolite production. Their enhanced production under biotic/abiotic stress factors accounts for better survival rates of cells, and thereby cyanobacteria are as an enticing source of bioactive compounds. Previous studies have shown the potent activity of extracts and fractions from Pseudanabaena galeata (Böcher 1949) strain CCNP1313 against cancer cells and viruses. However, active agents remain unknown, as the selected peptides had no effect on the tested cell lines. Here, we present a bottom-up approach, pinpointing key structures involved in secondary metabolite production. Consisting of six replicons, a complete genome sequence of P. galeata strain CCNP1313 was found to carry genes for non-ribosomal peptide/polyketide synthetases embedded within chromosome spans (4.9 Mbp) and for a ribosomally synthesized peptide located on one of the plasmids (0.2 Mbp). Elucidation of metabolite synthesis pathways led to prediction of their structure. While none of the synthesis-predicted products were found in mass spectrometry analysis, unexplored synthetases are characterized by structural similarities to those producing potent bioactive compounds. Full article

The rhizosphere of plants contains a wide range of microorganisms that can be cultivated and used for the benefit of agricultural practices. From garden soil near the rhizosphere region, Strain ES10-3-2-2 was isolated, and the cells were Gram-negative, aerobic, non-spore-forming rods that were 0.3–0.8 µm in diameter and 1.5–2.5 µm in length. The neighbor-joining method on 16S rDNA similarity revealed that the strain exhibited the highest sequence similarities with “Fibrivirga algicola JA-25” (99.2%) and Fibrella forsythia HMF5405^T (97.3%). To further explore its biotechnological potentialities, we sequenced the complete genome of this strain employing the PacBio RSII sequencing platform. The genome of Strain ES10-3-2-2 comprises a 6,408,035 bp circular chromosome with a 52.8% GC content, including 5038 protein-coding genes and 52 RNA genes. The sequencing also identified three plasmids measuring 212,574 bp, 175,683 bp, and 81,564 bp. Intriguingly, annotations derived from the NCBI-PGAP, eggnog, and KEGG databases indicated the presence of genes affiliated with radiation-resistance pathway genes and plant-growth promotor key/biofertilization-related genes regarding Fe acquisition, K and P assimilation, CO₂ fixation, and Fe solubilization, with essential roles in agroecosystems, as well as genes related to siderophore regulation. Additionally, T1SS, T6SS, and T9SS secretion systems are present in this species, like plant-associated bacteria. The inoculation of Strain ES10-3-2-2 to Arabidopsis significantly increases the fresh shoot and root biomass, thereby maintaining the plant quality compared to uninoculated controls. This work represents a link between radiation tolerance and the plant-growth mechanism of Strain ES10-3-2-2 based on in vitro experiments and bioinformatic approaches. Overall, the radiation-tolerant bacteria might enable the development of microbiological preparations that are extremely effective at increasing plant biomass and soil fertility, both of which are crucial for sustainable agriculture. Full article