The human uterus is traditionally believed to be sterile, while the vaginal microbiota plays an important role in fending off pathogens. Emerging evidence demonstrates the presence of bacteria beyond the vagina. However, a microbiome-wide metagenomic analysis characterizing the diverse microbial communities has been lacking.
Staphylococcus aureus poses a severe public health problem as one of the vital causative agents of healthcare- and community-acquired infections. There is a globally urgent need for new drugs with a novel mode of action (MoA) to combat S. aureus biofilms and persisters that tolerate antibiotic treatment. We demonstrate that a benzonaphthopyranone glycoside, chrysomycin A (ChryA), is a rapid bactericide that is highly active against S. aureus persisters, robustly eradicates biofilms in vitro, and shows a sustainable killing efficacy in vivo. ChryA was suggested to target multiple critical cellular processes. A wide range of genetic and biochemical approaches showed that ChryA directly binds to GlmU and DapD, involved in the biosynthetic pathways for the cell wall peptidoglycan and lysine precursors, respectively, and inhibits the acetyltransferase activities by competition with their mutual substrate acetyl-CoA. Our study provides an effective antimicrobial strategy combining multiple MoAs onto a single small molecule for treatments of S. aureus persistent infections.
Abstract Unsaturated fatty acids (UFAs) are essential for functional membrane phospholipids in most bacteria. The bifunctional dehydrogenase/isomerase FabX is an essential UFA biosynthesis enzyme in the widespread human pathogen Helicobacter pylori , a bacterium etiologically related to 95% of gastric cancers. Here, we present the crystal structures of FabX alone and in complexes with an octanoyl-acyl carrier protein (ACP) substrate or with holo-ACP. FabX belongs to the nitronate monooxygenase (NMO) flavoprotein family but contains an atypical [4Fe-4S] cluster absent in all other family members characterized to date. FabX binds ACP via its positively charged α7 helix that interacts with the negatively charged α2 and α3 helices of ACP. We demonstrate that the [4Fe-4S] cluster potentiates FMN oxidation during dehydrogenase catalysis, generating superoxide from an oxygen molecule that is locked in an oxyanion hole between the FMN and the active site residue His182. Both the [4Fe-4S] and FMN cofactors are essential for UFA synthesis, and the superoxide is subsequently excreted by H. pylori as a major resource of peroxide which may contribute to its pathogenic function in the corrosion of gastric mucosa.
Metasomatic alteration of fluorapatite has been reported in several iron-oxide apatite (IOA) deposits, but its effect on elemental and isotopic variations has not been well understood. In this study, we present integrated elemental, U-Pb, Sr, and O isotopic microanalytical data on fresh and altered domains in fluorapatite from the Taocun IOA deposit, Eastern China, to evaluate the timing and nature of the metasomatism and its effects on the ore-forming event. Orebodies of the Taocun deposit are spatially associated with a subvolcanic, intermediate intrusion, which displays zonal alteration patterns with albite in the center and increasing actinolite, chlorite, epidote, and carbonate toward the margin. Both disseminated and vein-type ores are present in the Taocun deposit, and fluorapatite commonly occurs with magnetite and actinolite in most ores.
Abstract High-titanium (high-Ti, more than 1 wt % Ti) magnetite, commonly containing ilmenite exsolution, has long been attributed to an igneous origin and has been used as the most critical factor in previously developed discriminant diagrams. However, recent studies have shown that high-Ti magnetite can be present in high-temperature hydrothermal deposits, suggesting a probable hydrothermal origin. This also calls for reconsideration and necessary modification of the currently available discriminant diagrams. This high-Ti magnetite issue is particularly acute in iron oxide-apatite (IOA) deposits and raises controversy in the discussion of the origin of the high-Ti magnetite. With statistical analysis and machine learning techniques, this study applies two unsupervised dimensionality reduction methods—principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE)—on a compiled data set consisting of 876 laser ablation-inductively coupled plasma-mass spectrometry analyses of primary high-Ti magnetite from high-temperature ore-forming systems worldwide. Three models are built with different element combinations to identify magnetite of different origins. The models were further evaluated by the support vectors machine (SVM) and receiver operating characteristic (ROC) curves and proved to be able to describe the characteristics of trace element compositions of high-Ti magnetite of different origins. Our models suggest that Mg, Mn, Al, Ti, V, and Co from 59 analyzed trace elements show promising properties as effective discriminators, and on this basis, a new discrimination diagram of lg(Al) + lg(Ti) + lg(V) versus lg(Mn)/[lg(Co) + lg(Mg)] is developed for distinguishing high-Ti magnetite of igneous and hydrothermal origin. Our results also show that the high-Ti magnetite in the IOA deposits has chemical compositions similar to those of high-temperature hydrothermal deposits, including the iron oxide copper-gold and porphyry deposits, but significantly distinct from the igneous magnetite. Our study, hence, implies a magmatic-hydrothermal origin for the magnetite in IOA deposits.
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