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.

Meningitis

The term aseptic meningitis encompasses all types of inflammations of the brain meninges other than that caused by pus producing organisms. It is usually a mild illness. Etiology of aseptic meningitis is very wide and includes many infections - both viral and non viral, drugs, malignancy and systemic illness. The most common cause is viral infection and enteroviruses - Coxsackie and ECHO viruses account for more than half of all cases. Clinical manifestations include headache, fever, malaise, photophobia and meningeal signs. Convulsions, neurological deficits and severe obtundation are rare except with certain non viral infectious meningitis. Diagnostic work up includes blood and cerebrospinal fluid (CSF) examination and serology for infectious meningitis. The polymerase chain reaction is a rapid and accurate method for detection of microbial DNA in CSF. Treatment is mainly supportive, except for the nonviral infectious etiology.

Bacterial composition and inferring function profiles in the biofloc system rearing Litopenaeus vannamei postlarvae at a low salinity

This study aimed to investigate the bacterial composition and inferring function profiles in the biofloc system rearing Litopenaeus vannamei postlarvae (PL) at a low salinity condition. PL (~ stage 15) were stocked in four parallel tanks filled in water with a salinity of 5.0‰ at a density of 4000 individuals per m3 for a 28-days culture experiment, during which glucose was added as carbon source with a C:N of 20:1. At the end of experiment, water was sampled from each tank and pooled to extract microbial DNA for high-throughput sequencing of V3-V4 region of 16S rRNA gene. Results showed that the bacterial community at 28 d was dominated by phyla of Proteobacteria (45.8%), Bacteroidetes (21.1%), Planctomycetes (13.5%), Chlamydiae (10.3%) and Firmicutes (6.8%). A proportion of 81% inferring KEGG functions of this bacterial community associated with metabolism. Among functions relating to nitrogen metabolism, 48.5% were involved in the conversion of ammonia to glutamate, but the proportion of those involved in transformation among ammonia, nitrite and nitrate was 18.0% in total, inferring higher protein-synthesis but lower inorganic nitrogen-transformation capacities of the bacterial community. At the same time (28 d), high levels of total nitrogen (231.3±6.0 mg L-1) and biofloc (127.0±63.0 mL L-1), but low concentrations of ammonia (0.04±0.01 mg L-1), nitrite (0.2±0.1 mg L-1) and nitrate (12.9±2.5 mg L-1) were observed. The results supply a novel insight for understanding the function of bacterial community in the biofloc system nursing L. vannamei PL at a low salinity.

In vitro behavior of Mycoplasmagallisepticum live-type nosode

As a step of a doctoral research project, in this study a live-type nosode was prepared from microorganism Mycoplasmagallisepticum strain R (ATCC 93-08/19610) according to Costa model and the rules by Brazilian Homeopathic Pharmacopoeia. Live nosode was tested in vitro to assess safety when used to immunize domestic fowl (Gallus gallus) against infection by this microorganism and to investigate its behavior under laboratory conditions. M. gallisepticum was not shown to grow in fluid (broth) and solid (plate) modified Frey medium with dilutions 11d, 12d, 20d and 30d. Inhibition halos about 2.0 mm were observed around paper disks impregnated with live-type nosode in microorganism-sown Petri dishes, whereas disks impregnated with conventional antibiotic oxytetracycline exhibited 8.0 mm inhibition halos. Protein assessment by Folin-Lowry method showed protein absence in dilutions 12d and 30d and neither microbial DNA traces were found in PCR assay in dilutions 12d, 20d and 30d.

STING-Mediated Interferon Induction by Herpes Simplex Virus 1 Requires the Protein Tyrosine Kinase Syk

The innate immune response to virus infection leads to interferon production and inhibition of viral replication. STING, an ER-bound protein, mediates such a response to cytoplasmic cellular or microbial DNA.

The Value of Vaginal Microbiome in Patients with Endometrial Hyperplasia

Objective. To investigate the profiles of the vaginal microbiome in patients with endometrial hyperplasia and to explore the potential value of vaginal microbiome in the diagnosis of endometrial hyperplasia. Materials/Methods. 26 patients suffering from abnormal uterine bleeding (AUB) with thickened endometrium revealed by transvaginal ultrasonography were enrolled. Based on pathology, 12 patients with endometrial hyperplasia were classified as the Veh group and 14 patients with proliferative endometrium were classified as the Vne group. The vaginal samples were collected for the presence of microbial DNA by high-throughput next-generation sequencing of the 16S rRNA gene. The α-diversity and ß-diversity of vaginal microbiome were analyzed and compared between bacterial populations. The ROC curve was made to evaluate the feasibility of flora as a biomarker. Results. The diversity of vaginal microbiome in the Veh group was significantly lower than that in the Vne group ( P < 0.05 ). Lactobacillus was the most represented genus in the Veh group. The study’s t-test between the two groups showed that Lactobacillus has the only significant difference in the abundance of the first 15 genera ( P < 0.01 ). ROC analysis of the abundance of Lactobacillus showed that the area of AUC was 0.83, the sensitivity was 93.00%, and the specificity was 75.00%. Conclusion. The study offers insight into the nature of the vaginal microbiome and suggests that surveying the vaginal microbiota might be useful for detection of endometrial hyperplasia.

Occurrence of Antimicrobial Resistance Genes in the Oral Cavity of Cats with Chronic Gingivostomatitis

Feline chronic gingivostomatitis (FCGS) is a severe immune-mediated inflammatory disease with concurrent oral dysbiosis (bacterial and fungal). Broad-spectrum antibiotics are used empirically in FCGS. Still, neither the occurrence of antimicrobial-resistant (AMR) bacteria nor potential patterns of co-occurrence between AMR genes and fungi have been documented in FCGS. This study explored the differential occurrence of AMR genes and the co-occurrence of AMR genes with oral fungal species. Briefly, 14 clinically healthy (CH) cats and 14 cats with FCGS were included. Using a sterile swab, oral tissue surfaces were sampled and submitted for 16S rRNA and ITS-2 next-generation DNA sequencing. Microbial DNA was analyzed using a proprietary curated database targeting AMR genes found in bacterial pathogens. The co-occurrence of AMR genes and fungi was tested using point biserial correlation. A total of 21 and 23 different AMR genes were detected in CH and FCGS cats, respectively. A comparison of AMR-gene frequencies between groups revealed statistically significant differences in the occurrence of genes conferring resistance to aminoglycosides (ant4Ib), beta-lactam (mecA), and macrolides (mphD and mphC). Two AMR genes (mecA and mphD) showed statistically significant co-occurrence with Malassezia restricta. In conclusion, resistance to clinically relevant antibiotics, such as beta-lactams and macrolides, is a significant cause for concern in the context of both feline and human medicine.

Macrophages in dermal disease progression of phospholipase D4–deficient Fleckvieh calves

A new gene defect in Fleckvieh calves leads to a syndrome with partial phenotype overlap with bovine hereditary zinc deficiency. A mutation in a gene encoding phospholipase D4 ( PLD4), an endosomal exonuclease, causes the disorder. In mice, PLD4 activity indirectly regulates the Toll-like receptor 9 (TLR9) pathway via degradation of microbial DNA. PLD4 absence thus results in visceral macrophage activation comparable to human macrophage activation syndrome. In this study, disease progression and the role of macrophages in affected calves were monitored clinically, clinicopathologically, and histologically over time. Breeding data identified 73 risk matings of heterozygous carriers resulting in 54 potentially PLD4-deficient calves born on farms. PLD4 status was examined via 5′-exonuclease assay, detecting 6 calves carrying the defect. These were purchased and monitored daily until final necropsy. The calves developed progressive skin lesions starting with small scaling areas terminating in severe crusting dermatitis, especially in areas with mechanical exposure. Histological and immunohistochemical analyses indicated that macrophages with cytoplasmic vacuolation increased considerably in skin sections obtained weekly during the disease course. Macrophage increase correlated with increased dermal lesion severity. Macrophage activation was confirmed by prominent phagocytic activity in the superficial dermis using electron microscopy. Dermal mRNA abundance of CCL2 and CCL3 measured by quantitative polymerase chain reaction verified macrophage activation. Further increase in mRNA of downstream molecule MyD88 and cytokine IL12b connected bovine PLD4 deficiency to increased TLR9 pathway activation. In contrast to human macrophage activation syndrome, the main feature of bovine PLD4 deficiency was local disease in organs with contact to microbial DNA (skin, intestine, lungs).