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Background: Klebsiella pneumoniae causes severe diseases including sepsis, pneumonia
and wound infections and is differentiated into hypervirulent (hvKp) and classic (cKp) pathotypes.
hvKp isolates are characterized clinically by invasive and multiple site infection and phenotypically
in particular through hypermucoviscosity and increased siderophore production, enabled by the
presence of the respective virulence genes, which are partly carried on plasmids. Methods: Here, we
analyzed two K. pneumoniae isolates of a human patient that caused severe multiple site infection.
By applying both genomic and phenotypic experiments and combining basic science with clinical
approaches, we aimed at characterizing the clinical background as well as the two isolates in-depth.
This also included bioinformatics analysis of a chromosomal virulence plasmid integration event.
Results: Our genomic analysis revealed that the two isolates were clonal and belonged to sequence
type 420, which is not only the first description of this K. pneumoniae subtype in Germany but also
suggests belonging to the hvKp pathotype. The latter was supported by the clinical appearance and
our phenotypic findings revealing increased siderophore production and hypermucoviscosity similar
to an archetypical, hypervirulent K. pneumoniae strain. In addition, our in-depth bioinformatics
analysis suggested the insertion of a hypervirulence plasmid in the bacterial chromosome, mediated
by a new IS5 family sub-group IS903 insertion sequence designated ISKpn74. Conclusion: Our study
contributes not only to the understanding of hvKp and the association between hypervirulence and
clinical outcomes but reveals the chromosomal integration of a virulence plasmid, which might lead
to tremendous public health implications.
Proteasomes comprise a family of proteasomal complexes essential for maintaining protein homeostasis. Accordingly, proteasomes represent promising therapeutic targets in multiple human diseases. Several proteasome inhibitors are approved for treating hematological cancers. However, their side effects impede their efficacy and broader therapeutic applications. Therefore, understanding the biology of the different proteasome complexes present in the cell is crucial for developing tailor-made inhibitors against specific proteasome complexes. Here, we will discuss the structure, biology, and function of the alternative Proteasome Activator 200 (PA200), also known as PSME4, and summarize the current evidence for its dysregulation in different human diseases. We hereby aim to stimulate research on this enigmatic proteasome regulator that has the potential to serve as a therapeutic target in cancer.
Four aerobic bacteria with bacteriolytic capabilities were isolated from the brackish water site Strait Uzynaral of Lake Balkhash in Kazakhstan. The morphology and physiology of the bacterial isolates have subsequently been analyzed. Using matrix assisted laser desorption ionization-time of flight mass spectrum and partial 16S rRNA gene sequence analyses, three of the isolates have been identified as Pseudomonas veronii and one as Paenibacillus apiarius. We determined the capability of both species to lyse pre-grown cells of the Gram-negative strains Pseudomonas putida SBUG 24 and Escherichia coli SBUG 13 as well as the Gram-positive strains Micrococcus luteus SBUG 16 and Arthrobacter citreus SBUG 321 on solid media. The bacteriolysis process was analyzed by creating growth curves and electron micrographs of co-cultures with the bacteriolytic isolates and the lysis sensitive strain Arthrobacter citreus SBUG 321 in nutrient-poor liquid media. One metabolite of Paenibacillus apiarius was isolated and structurally characterized by various chemical structure determination methods. It is a novel antibiotic substance.
The main goal of this contribution was to determine the effect of predation of the often abundant to dominant doliolid Dolioletta gegenbauri (Tunicata, Thaliacea) on the abundance of co-occurring planktonic copepods by feeding on their eggs. Previous oceanographic investigations revealed that doliolids had ingested eggs of small calanoid copepods. The ecological significance of such feeding could not be quantified completely because the environmental abundance of such eggs was not known. In this study, the eggs and nauplii of the neritic calanoid Paracalanus quasimodo (Crustacea, Copepoda) were offered to gonozooids and phorozooids of D. gegenbauri with a 6–6.5 mm length together with three species of phytoplankton; i.e., simulating diet conditions on the shelf. We hypothesized that copepod eggs of a similar size as food particles would be readily ingested whereas small nauplii, which could escape, would hardly be eaten by the doliolids. Our results revealed that doliolids have the potential to control small calanoids by ingesting their eggs at high rates but not their nauplii or later stages. Late copepodid stages and adults of co-occurring calanoid species could cause less mortality because they prey less on such eggs than doliolids of a similar weight. However, certain abundant omnivorous calanoid species with pronounced perception and/or capture abilities can prey successfully on the nauplii of small calanoids.
MicroRNAs (miRNA) are ubiquitous non-coding RNAs that have a prominent role in cellular regulation. The expression of many miRNAs is often found deregulated in prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). Although their expression can be associated with PCa and CRPC, their functions and regulatory activity in cancer development are poorly understood. In this study, we used different proteomics tools to analyze the activity of hsa-miR-3687-3p (miR-3687) and hsa-miR-4417-3p (miR-4417), two miRNAs upregulated in CRPC. PCa and CRPC cell lines were transfected with miR-3687 or miR-4417 to overexpress the miRNAs. Cell lysates were analyzed using 2D gel electrophoresis and proteins were subsequently identified using mass spectrometry (Maldi-MS/MS). A whole cell lysate, without 2D-gel separation, was analyzed by ESI-MS/MS. The expression of deregulated proteins found across both methods was further investigated using Western blotting. Gene ontology and cellular process network analysis determined that miR-3687 and miR-4417 are involved in diverse regulatory mechanisms that support the CRPC phenotype, including metabolism and inflammation. Moreover, both miRNAs are associated with extracellular vesicles, which point toward a secretory mechanism. The tumor protein D52 isoform 1 (TD52-IF1), which regulates neuroendocrine trans-differentiation, was found to be substantially deregulated in androgen-insensitive cells by both miR-3687 and miR-4417. These findings show that these miRNAs potentially support the CRPC by truncating the TD52-IF1 expression after the onset of androgen resistance.
Multidrug-resistant (MDR) Enterobacterales, including extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, not only emerge in healthcare settings but also in other habitats, such as livestock and wildlife. The spread of these pathogens, which often combine resistance with high-level virulence, is a growing problem, as infections have become increasingly difficult to treat. Here, we investigated the occurrence of ESBL-producing E. coli and K. pneumoniae in fecal samples from two black-headed gull colonies breeding on two nature conservation islands in Western Pomerania, Germany. In addition to cloacal samples from adult birds (n = 211) and their nestlings (n = 99) during the 2021 breeding season, collective fecal samples (n = 29) were obtained. All samples were screened for ESBL producers, which were then subjected to whole-genome sequencing. We found a total of 12 ESBL-producing E. coli and K. pneumoniae consisting of 11 E. coli and 1 K. pneumoniae, and including the international high-risk E. coli sequence types (ST)131, ST38, and ST58. Eight of the investigated strains had a MDR genotype and carried a large repertoire of virulence-associated genes, including the pap operon, which is important for urinary tract infections. In addition, we identified many genes associated with adherence, biofilm formation, iron uptake, and toxin production. Finally, our analysis revealed the close phylogenetic relationship of ST38 strains with genomes originating from human sources, underlining their zoonotic and pathogenic character. This study highlights the importance of the One Health approach, and thus the interdependence between human and animal health and their surrounding environment.
Re-Establishment Techniques and Transplantations of Charophytes to Support Threatened Species
(2021)
Re-establishment of submerged macrophytes and especially charophyte vegetation is a common aim in lake management. If revegetation does not happen spontaneously, transplantations may be a suitable option. Only rarely have transplantations been used as a tool to support threatened submerged macrophytes and, to a much lesser extent, charophytes. Such actions have to consider species-specific life strategies. K-strategists mainly inhabit permanent habitats, are perennial, have low fertility and poor dispersal ability, but are strong competitors and often form dense vegetation. R-strategists are annual species, inhabit shallow water and/or temporary habitats, and are richly fertile. They disperse easily but are weak competitors. While K-strategists easily can be planted as green biomass taken from another site, rare R-strategists often must be reproduced in cultures before they can be planted on-site. In Sweden, several charophyte species are extremely rare and fail to (re)establish, though apparently suitable habitats are available. Limited dispersal and/or lack of diaspore reservoirs are probable explanations. Transplantations are planned to secure the occurrences of these species in the country. This contribution reviews the knowledge on life forms, dispersal, establishment, and transplantations of submerged macrophytes with focus on charophytes and gives recommendations for the Swedish project.
Proteomic Adaptation of Clostridioides difficile to Treatment with the Antimicrobial Peptide Nisin
(2021)
Urm1: A Non-Canonical UBL
(2021)
Glutathione (GSH) was initially identified and characterized for its redox properties andlater for its contributions to detoxification reactions. Over the past decade, however, the essentialcontributions of glutathione to cellular iron metabolism have come more and more into focus. GSH isindispensable in mitochondrial iron-sulfur (FeS) cluster biosynthesis, primarily by co-ligating FeSclusters as a cofactor of the CGFS-type (class II) glutaredoxins (Grxs). GSH is required for the exportof the yet to be defined FeS precursor from the mitochondria to the cytosol. In the cytosol, it is anessential cofactor, again of the multi-domain CGFS-type Grxs, master players in cellular iron and FeStrafficking. In this review, we summarize the recent advances and progress in this field. The mosturgent open questions are discussed, such as the role of GSH in the export of FeS precursors frommitochondria, the physiological roles of the CGFS-type Grx interactions with BolA-like proteins andthe cluster transfer between Grxs and recipient proteins