Summary
Clostridia comprise bacteria of environmental, biotechnological and medical interest and many commensals of the gut microbiota. Because of their strictly anaerobic lifestyle, oxygen is a ...major stress for Clostridia. However, recent data showed that these bacteria can cope with O2 better than expected for obligate anaerobes through their ability to scavenge, detoxify and consume O2. Upon O2 exposure, Clostridia redirect their central metabolism onto pathways less O2‐sensitive and induce the expression of genes encoding enzymes involved in O2‐reduction and in the repair of oxidized damaged molecules. While Faecalibacterium prausnitzii efficiently consumes O2 through a specific extracellular electron shuttling system requiring riboflavin, enzymes such as rubrerythrins and flavodiiron proteins with NAD(P)H‐dependent O2‐ and/or H2O2‐reductase activities are usually encoded in other Clostridia. These two classes of enzymes play indeed a pivotal role in O2 tolerance in Clostridioides difficile and Clostridium acetobutylicum. Two main signalling pathways triggering O2‐induced responses have been described so far in Clostridia. PerR acts as a key regulator of the O2‐ and/or reactive oxygen species–defence machinery while in C. difficile, σB, the sigma factor of the general stress response also plays a crucial role in O2 tolerance by controlling the expression of genes involved in O2 scavenging and repair systems.
The thioredoxin (Trx) system, found universally, is responsible for the regeneration of reversibly oxidized protein thiols in living cells. This system is made up of a Trx and a Trx reductase, and it ...plays a central role in maintaining thiol‐based redox homeostasis by reducing oxidized protein thiols, such as disulfide bonds in proteins. Some Trxs also possess a chaperone function that is independent of thiol‐disulfide exchange, in addition to their thiol‐disulfide reductase activity. These two activities of the Trx system are involved in numerous physiological processes in bacteria. This review describes the diverse physiological roles of the Trx system that have emerged throughout bacterial evolution. The Trx system is essential for responding to oxidative and nitrosative stress. Beyond this primary function, the Trx system also participates in redox regulation and signal transduction, and in controlling metabolism, motility, biofilm formation, and virulence. This range of functions has evolved alongside the diversity of bacterial lifestyles and their specific constraints. This evolution can be characterized by the multiplication of the systems and by the specialization of cofactors or targets to adapt to the constraints of atypical lifestyles, such as photosynthesis, insect endosymbiosis, or spore‐forming bacteria.
The thioredoxin (Trx) system, an ancestral and ubiquitous mechanism, maintains thiol homeostasis. The prolonged co‐evolution of this system with bacteria has resulted in a broad spectrum of physiological roles. Bacterial Trx systems play a significant part in numerous key processes, including response to stress, metabolism, regulatory cascades, motility, biofilm formation, and virulence.
Grapevine (
Vitis vinifera
L.) is one of the most important crops worldwide but is subjected to multiple biotic and abiotic stresses, especially related to climate change. In this context, the ...grapevine culture could take advantage of symbiosis through association with arbuscular mycorrhizal fungi (AMF), which are able to establish symbiosis with most terrestrial plants. Indeed, it is well established that mycorrhization improves grapevine nutrition and resistance to stresses, especially water stress and resistance to root pathogens. Thus, it appears essential to understand the effect of mycorrhization on grapevine metabolism and defense responses. In this study, we combined a non-targeted metabolomic approach and a targeted transcriptomic study to analyze changes induced in both the roots and leaves of
V. vinifera
cv. Gewurztraminer by colonization with
Rhizophagus irregularis
(Ri). We showed that colonization of grapevine with AMF triggers major reprogramming of primary metabolism in the roots, especially sugar and fatty acid metabolism. On the other hand, mycorrhizal roots had decreased contents of most sugars and sugar acids. A significant increase in several fatty acids (C16:1, linoleic and linolenic acids and the C20 arachidonic and eicosapentaenoic acids) was also detected. However, a downregulation of the JA biosynthesis pathway was evidenced. We also found strong induction of the expression of PR proteins from the proteinase inhibitor (PR6) and subtilase (PR7) families in roots, suggesting that these proteins are involved in the mycorrhiza development but could also confer higher resistance to root pathogens. Metabolic changes induced by mycorrhization were less marked in leaves but involved higher levels of linoleic and linolenic acids and decreased sucrose, quinic, and shikimic acid contents. In addition, Ri colonization resulted in enhanced JA and SA levels in leaves. Overall, this study provides a detailed picture of metabolic changes induced by AMF colonization in a woody, economically important species. Moreover, stimulation of fatty acid biosynthesis and PR protein expression in roots and enhanced defense hormone contents in leaves establish first insight in favor of better resistance of grapevine to various pathogens provided by AMF colonization.
Spectroscopic techniques such as Fourier-transform infrared (FTIR) spectroscopy are used to study interactions of light with biological materials. This interaction forms the basis of many analytical ...assays used in disease screening/diagnosis, microbiological studies, and forensic/environmental investigations. Advantages of spectrochemical analysis are its low cost, minimal sample preparation, non-destructive nature and substantially accurate results. However, an urgent need exists for repetition and validation of these methods in large-scale studies and across different research groups, which would bring the method closer to clinical and/or industrial implementation. For this to succeed, it is important to understand and reduce the effect of random spectral alterations caused by inter-individual, inter-instrument and/or inter-laboratory variations, such as variations in air humidity and CO
levels, and aging of instrument parts. Thus, it is evident that spectral standardization is critical to the widespread adoption of these spectrochemical technologies. By using calibration transfer procedures, in which the spectral response of a secondary instrument is standardized to resemble the spectral response of a primary instrument, different sources of variation can be normalized into a single model using computational-based methods, such as direct standardization (DS) and piecewise direct standardization (PDS); therefore, measurements performed under different conditions can generate the same result, eliminating the need for a full recalibration. Here, we have constructed a protocol for model standardization using different transfer technologies described for FTIR spectrochemical applications. This is a critical step toward the construction of a practical spectrochemical analysis model for daily routine analysis, where uncertain and random variations are present.
Objectives
Our objective was to identify missed opportunities for the use of pre‐exposure prophylaxis (PrEP) in people with recently acquired HIV, factors associated with PrEP knowledge, and reasons ...for not using PrEP.
Design
This was a French national cross‐sectional multicentre study enrolling people diagnosed with recent HIV (incomplete Western blot or negative HIV test in the previous 6 months) in 28 HIV clinical centres. Data were gathered using a self‐administered questionnaire (SAQ).
Method
We analysed missed opportunities for PrEP use via a retrospective prep cascade. Factors associated with prior knowledge of PrEP and reasons for PrEP non‐use among those who knew about PrEP were described using univariate and multivariate logistic regression models.
Results
Of the 224 eligible patients, 185 completed the SAQ and 168 (91%) were eligible for PrEP. Of these, 90% reported seeing at least one physician during the previous year, 26% received information about PrEP, and 5% used PrEP. Factors independently associated with a higher probability of knowing about PrEP were being a man who has sex with men, being aged 25–30 years (vs older), undergoing HIV screening at least once every semester (vs less often; odds ratio OR 4.11; 95% confidence interval CI 2.00–8.45), and practicing chemsex (OR 3.19; 95% CI 1.12–9.10). Fear of side effects and a low perceived risk of HIV infection were the two most common reasons for not using PrEP (N = 40 33.33% and N = 34 28.3%, respectively).
Conclusions
We found two gaps in the retrospective PrEP cascade: insufficient provision of PrEP information by healthcare providers (mainly general practitioners) and low PrEP acceptability by informed, eligible patients. More diverse healthcare providers need to be involved in PrEP prescription, and at‐risk people need to be sensitized to the risk of HIV infection.
The chemical stability and caesium retention properties of a nonstoichiometric compoundK2-xNix/2NiFe(CN)6.nH2O (KNiFCN) was studied in different pH conditions. Different solutions with controlled pH ...were prepared. Leaching tests were done with chemical analysis of the solutions. The compound was characterized before and after exposure by chemical analysis, SEM-BSE, X-ray diffraction and infrared spectroscopy. The face-centered cubic (FCC) structure of KNiFCN without caesium was stable even in presence of 1 g/l HNO3 (pH equal 2) or NaOH (pH equal 13). In presence of caesium trapped on KNiFCN structure, it appears that the increase in caesium content change the KNiFCN structure, thus influencing the retention properties in KNiFCN according to the pH of the solution. The KNiFCN structure was decomposed when the NaOH concentration exceeds 1 g/l (pH equal 14), probably due to the hydrolysis of constitutional elements. A selection of cementitious matrix is the proposed to satisfy stability conditions of this compound.
Overview of the KNiFCN and KNiFCN–Cs stability study as a function of pH. Display omitted
•The increase in caesium sorbed changed the structure of KNiFCN, influencing the caesium sorption capacity as function of pH.•In basic condition, a change of chemical environment of the ferrocyanure compounds was observed.•Precipitation of new compounds –such as nickel and/or iron hydroxide (Ni(OH)2, Fe(OH)2 and/or Fe(OH)3.(H2O)), was shown.•In order to ensure the sludge conditioning for nuclear process, the cementing system will have to satisfy pHs below 12.
Altered cellular metabolism is a hallmark of tumor cells and contributes to a host of properties associated with resistance to radiotherapy. Detection of radiation-induced biochemical changes can ...reveal unique metabolic pathways affecting radiosensitivity that may serve as attractive therapeutic targets. Using clinically relevant doses of radiation, we performed label-free single cell Raman spectroscopy on a series of human cancer cell lines and detected radiation-induced accumulation of intracellular glycogen. The increase in glycogen post-irradiation was highest in lung (H460) and breast (MCF7) tumor cells compared to prostate (LNCaP) tumor cells. In response to radiation, the appearance of this glycogen signature correlated with radiation resistance. Moreover, the buildup of glycogen was linked to the phosphorylation of GSK-3β, a canonical modulator of cell survival following radiation exposure and a key regulator of glycogen metabolism. When MCF7 cells were irradiated in the presence of the anti-diabetic drug metformin, there was a significant decrease in the amount of radiation-induced glycogen. The suppression of glycogen by metformin following radiation was associated with increased radiosensitivity. In contrast to MCF7 cells, metformin had minimal effects on both the level of glycogen in H460 cells following radiation and radiosensitivity. Our data demonstrate a novel approach of spectral monitoring by Raman spectroscopy to assess changes in the levels of intracellular glycogen as a potential marker and resistance mechanism to radiation therapy.
The pathogenic clostridia cause many human and animal diseases, which typically arise as a consequence of the production of potent exotoxins. Among the enterotoxic clostridia, Clostridium difficile ...is the main causative agent of nosocomial intestinal infections in adults with a compromised gut microbiota caused by antibiotic treatment. The symptoms of C. difficile infection are essentially caused by the production of two exotoxins: TcdA and TcdB. Moreover, for severe forms of disease, the spectrum of diseases caused by C. difficile has also been correlated to the levels of toxins that are produced during host infection. This observation strengthened the idea that the regulation of toxin synthesis is an important part of C. difficile pathogenesis. This review summarizes our current knowledge about the regulators and sigma factors that have been reported to control toxin gene expression in response to several environmental signals and stresses, including the availability of certain carbon sources and amino acids, or to signaling molecules, such as the autoinducing peptides of quorum sensing systems. The overlapping regulation of key metabolic pathways and toxin synthesis strongly suggests that toxin production is a complex response that is triggered by bacteria in response to particular states of nutrient availability during infection.
Summary
The strict anaerobe Clostridium difficile is the most common cause of antibiotic‐associated diarrhoea. The oxygen‐resistant C. difficile spores play a central role in the infectious cycle, ...contributing to transmission, infection and recurrence. The spore surface layers, the coat and exosporium, enable the spores to resist physical and chemical stress. However, little is known about the mechanisms of their assembly. In this study, we characterized a new spore protein, CotL, which is required for the assembly of the spore coat. The cotL gene was expressed in the mother cell compartment under the dual control of the RNA polymerase sigma factors, σE and σK. CotL was localized in the spore coat, and the spores of the cotL mutant had a major morphologic defect at the level of the coat/exosporium layers. Therefore, the mutant spores contained a reduced amount of several coat/exosporium proteins and a defect in their localization in sporulating cells. Finally, cotL mutant spores were more sensitive to lysozyme and were impaired in germination, a phenotype likely to be associated with the structurally altered coat. Collectively, these results strongly suggest that CotL is a morphogenetic protein essential for the assembly of the spore coat in C. difficile.
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