Arene-Ruthenium(II) Complexes with Carbothiamidopyrazoles as a Potential Alternative for Antibiotic Resistance in Human.

To meet the demand for alternatives to commonly used antibiotics, this paper evaluates the antimicrobial potential of arene-ruthenium(II) complexes and their salts, which may be of value in antibacterial treatment. Their antimicrobial activity (MIC, MBC/MFC) was examined in vitro against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus vulgaris and Candida albicans and compared with classic antibiotics used as therapeutics. Selected arene-ruthenium(II) complexes were found to have synergistic effects with oxacillin and vancomycin against staphylococci. Their bactericidal effect was found to be associated with cell lysis and the ability to cut microbial DNA. To confirm the safety of the tested arene-ruthenium(II) complexes in vivo, their cytotoxicity was also investigated against normal human foreskin fibroblasts (HFF-1). In addition, the antioxidant and thus pro-health potential of the compounds, i.e., their nonenzymatic antioxidant capacity (NEAC), was determined by two different methods: ferric-TPTZ complex and DPPH assay.

Staphylococcal species less frequently isolated from human clinical specimens - are they a threat for hospital patients?

BACKGROUND: Coagulase-negative staphylococci belonging to S. haemolyticus, S. hominis subsp. hominis, S. simulans, and S. warneri are often described as etiological factors of infections. Staphylococci are a phylogenetically coherent group; nevertheless, there are differences among the species which may be important to clinicians. METHODS: We investigated selected virulence factors and antibiotic resistance that were phenotypically demonstrated, the presence and expression of genes encoding the virulence factors, and the type of the SCCmec cassette. RESULTS: The differences between the tested species were revealed. A great number of isolates produced a biofilm and many of them contained single icaADBC operon genes. Clear differences between species in the lipolytic activity spectrum could be related to their ability to cause various types of infections. Our studies also revealed the presence of genes encoding virulence factors homologous to S. aureus in the analysed species such as enterotoxin and pvl genes, which were also expressed in single isolates of S. simulans and S. warneri. S. haemolyticus and S. hominis subsp. hominis isolates were resistant to all clinically important antibiotics including ß-lactams. The identified SCCmec cassettes belonged to IV, V, VII, and IX type but most of the detected cassettes were non-typeable. Among the investigated species, S. hominis subsp. hominis isolates accumulated virulence genes typical for S. aureus in the most efficient way and were widely resistant to antibiotics. CONCLUSIONS: Our results clearly indicated significant differences between the tested species, which might be a result of the horizontal gene transfer (HGT) and can lead to the formation and selection of multi-drug resistant strains as well as strains with new virulence features. Such strains can have a new clinical relevance.

Analysis of the Presence of the Virulence and Regulation Genes from Staphylococcus aureus (S. aureus) in Coagulase Negative Staphylococci and the Influence of the Staphylococcal Cross-Talk on Their Functions.

Coagulase-negative staphylococci (CoNS) are increasingly becoming a public health issue worldwide due to their growing resistance to antibiotics and common involvement in complications related to invasive surgical procedures, and nosocomial and urinary tract infections. Their behavior either as a commensal or a pathogen is a result of strict regulation of colonization and virulence factors. Although functionality of virulence factors and processes involved in their regulation are quite well understood in S. aureus, little is known about them in CoNS species. Therefore, the aim of our studies was to check if clinical CoNS strains may contain virulence factors and genes involved in resistance to methicillin, that are homologous to S. aureus. Moreover, we checked the presence of elements responsible for regulation of genes that encode virulence factors typical for S. aureus in tested isolates. We also investigated whether the regulation factors produced by one CoNS isolate can affect virulence activity of other strains by co-incubation of tested isolates with supernatant from other isolates. Our studies confirmed the presence of virulence factor and regulatory genes attributed to S. aureus in CoNS isolates and indicated that one strain with an active agr gene is able to affect biofilm formation and δ-toxin activity of strains with inactive agr genes. The cognition of prevalence and regulation of virulence factors as well as antibiotic resistance of CoNS isolates is important for better control and treatment of CoNS infections.

How to Naturally Support the Immune System in Inflammation-Essential Oils as Immune Boosters.

Efficient functionality of the immune system is needed to fight against the development of infectious diseases, including, among others, serious recurrent chronic infections. Research has shown that many modern common diseases, such as inflammatory bowel diseases and cardiovascular diseases, e.g., thromboembolism, cancer, obesity, or depression, are connected with inflammatory processes. Therefore, new, good stimulators of the immune system's response are sought. They include synthetic compounds as well as biological preparations such as lipopolysaccharides, enzymes, bacterial metabolites, and secondary metabolites of plants, demonstrating a multidirectional effect. Essential oils are characterized by many invaluable activities, including antimicrobial, antioxidant, anti-inflammatory, and immunostimulating. Essential oils may stimulate the immune system via the utilization of their constituents, such as antibodies, cytokines, and dendritic cells. Some essential oils may stimulate the proliferation of immune-competent cells, including polymorphonuclear leukocytes, macrophages, dendritic cells, natural killer cells, and B and T lymphocytes. This review is focused on the ability of essential oils to affect the immune system. It is also possible that essential oil components positively interact with recommended anti-inflammatory and antimicrobial drugs. Thus, there is a need to explore possible synergies between essential oils and their active ingredients for medical use.

Anticancer and antimicrobial properties of novel η6-p-cymene ruthenium(ii) complexes containing a N,S-type ligand, their structural and theoretical characterization.

Ruthenium(ii) complexes are lately of great scientific interest due to their chemotherapeutic potential as anticancer and antimicrobial agents. Here we present the synthesis of new pyrazole carbothioamide derivatives and their four arene-ruthenium complexes. The title compounds were characterized with the application of IR, NMR, mass spectrometry, elemental analysis and X-ray diffraction. Additionally, for new complexes DFT calculations were done. Their antimicrobial activity (MIC, MBC/MFC) was examined in vitro against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus vulgaris and Candida albicans. Their cytotoxic effects, using the MTT assay, against three cancer cell lines: HL-60, NALM-6, WM-115 and normal human foreskin fibroblasts (HFF-1) were also investigated. The influence of the new arene-ruthenium(ii) complexes on the DNA structure was also tested. From our results, compound 2d showed higher cytotoxicity against melanoma cell line WM-115 than cisplatin. Strong biostatic and biocidal activity of the tested complexes against Gram-positive bacteria, including S. aureus, S. epidermidis and E. faecalis was demonstrated. The new arene-ruthenium(ii) compounds could not only inhibit proliferation of cancer cells, but also protect patients against malignant wound infections.

Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma.

Tumor-driven immune suppression is a major barrier to successful immunotherapy in ovarian carcinomas (OvCa). Among various mechanisms responsible for immune suppression, arginase-1 (ARG1)-carrying small extracellular vesicles (EVs) emerge as important contributors to tumor growth and tumor escape from the host immune system. Here, we report that small EVs found in the ascites and plasma of OvCa patients contain ARG1. EVs suppress proliferation of CD4+ and CD8+ T-cells in vitro and in vivo in OvCa mouse models. In mice, ARG1-containing EVs are transported to draining lymph nodes, taken up by dendritic cells and inhibit antigen-specific T-cell proliferation. Increased expression of ARG1 in mouse OvCa cells is associated with accelerated tumor progression that can be blocked by an arginase inhibitor. Altogether, our studies show that tumor cells use EVs as vehicles to carry over long distances and deliver to immune cells a metabolic checkpoint molecule - ARG1, mitigating anti-tumor immune responses.

Synthesis, physico-chemical properties and biological analysis of newly obtained copper(II) complexes with pyrazole derivatives.

Three new copper(II) complexes containing two different pyrazole bound ligands (1, 2) have been synthesized and characterized by IR, LSI-MS (liquid secondary ion mass spectrometry) and elemental analysis. (1)H NMR spectra of the organic ligands have been recorded. We describe the influence of these complexes on particular cancer cell lines and DNA structure by MTT-assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], APA (acid phosphatase activity)-assay or CD-spectroscopy and agarose gel electrophoresis methods, together with their physico-chemical properties such as lipophilicity and stability in aqueous solution. The cytotoxic effect on HUVEC (endothelial cells) for the most active complex 4 has been also investigated. Moreover, the ability of these complexes to induce apoptosis in cancer cells has been assessed by using fluorescence microscopy. Our results indicate that dichloridobis{1-[amino(thioxo)methyl]-5-hydroxy-3-phenyl-1H-pyrazole-κN2}copper(II) is the most potent complex among the tested complexes.