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Mycobacterium kansasii can cause serious pulmonary disease. It belongs to a group of closely-related species of non-tuberculous mycobacteria known as the M. kansasii complex (MKC). Here, we report a population genomics analysis of 358 MKC isolates from worldwide water and clinical sources. We find that recombination, likely mediated by distributive conjugative transfer, has contributed to speciation and on-going diversification of the MKC. Our analyses support municipal water as a main source of MKC infections. Furthermore, nearly 80% of the MKC infections are due to closely-related M. kansasii strains, forming a main cluster that apparently originated in the 1900s and subsequently expanded globally. Bioinformatic analyses indicate that several genes involved in metabolism (e.g., maintenance of the methylcitrate cycle), ESX-I secretion, metal ion homeostasis and cell surface remodelling may have contributed to M. kansasii ’s success and its ongoing adaptation to the human host. Mycobacterium kansasii can cause serious pulmonary disease. Here, the authors present a population genomics analysis of 358 environmental and clinical isolates from around the world, supporting the idea that municipal water is a main source of infection, and shedding light into the pathogen’s diversity and adaptation to the human host.

Exposure to heavy metals, including cadmium (Cd), can induce neurotoxicity and cell death. Cd is abundant in the environment and accumulates in the striatum, the primary brain region selectively affected by Huntington’s disease (HD). We have previously reported that mutant huntingtin protein (mHTT) combined with chronic Cd exposure induces oxidative stress and promotes metal dyshomeostasis, resulting in cell death in a striatal cell model of HD. To understand the effect of acute Cd exposure on mitochondrial health and protein degradation pathways, we hypothesized that expression of mHTT coupled with acute Cd exposure would cooperatively alter mitochondrial bioenergetics and protein degradation mechanisms in striatal STHdh cells to reveal novel pathways that augment Cd cytotoxicity and HD pathogenicity. We report that mHTT cells are significantly more susceptible to acute Cd-induced cell death as early as 6 h after 40 µM CdCl2 exposure compared with wild-type (WT). Confocal microscopy, biochemical assays, and immunoblotting analysis revealed that mHTT and acute Cd exposure synergistically impair mitochondrial bioenergetics by reducing mitochondrial potential and cellular ATP levels and down-regulating the essential pro-fusion proteins MFN1 and MFN2. These pathogenic effects triggered cell death. Furthermore, Cd exposure increases the expression of autophagic markers, such as p62, LC3, and ATG5, and reduces the activity of the ubiquitin–proteasome system to promote neurodegeneration in HD striatal cells. Overall, these results reveal a novel mechanism to further establish Cd as a pathogenic neuromodulator in striatal HD cells via Cd-triggered neurotoxicity and cell death mediated by an impairment in mitochondrial bioenergetics and autophagy with subsequent alteration in protein degradation pathways.

Introduction: Cytomegalovirus (CMV) infection has long been recognized as an important viral syndrome in the immunocompromised host. The disease is less well described in critically-ill patients. We evaluated the risk factors for the development of CMV infection in patients admitted to the intensive care unit (ICU). We also compared the outcomes of CMV infection in ICU patients to those of patients with hematological malignancies. Methodology: This is a retrospective study composed of three arms: patients admitted to the ICU with infection (ICU + / CMV + arm), patients admitted to the ICU who did not develop CMV infection (ICU + / CMV- arm, and patients with hematological malignancies on the hematology ward without CMV infection (ICU - / CMV + arm). Results: Patients who were admitted to ICU for surgical causes had a decreased risk of CMV infection. On the other hand, receiving corticosteroids and vasoactive drugs was associated with an increased risk of CMV infection with adjusted odds ratios (aOR) of 2.4 and 25.3, respectively. Mortality was higher in ICU + / CMV + patients compared to ICU - / CMV + patients. In the ICU + /CMV + population, male sex and being on mechanical ventilation after CMV infection were independent predictors of mortality (aOR 4.6 and 5.0, respectively). Conclusions: CMV infection in ICU patients is a potentially serious disease requiring close attention. The findings from our study help in identifying patients in the ICU at risk for CMV infection, thereby warranting frequent screening. Patients at high risk of death (male, on mechanical ventilation) should receive prompt treatment and intensive follow-up.

Stress granules (SGs) are dynamic accumulations of stalled preinitiation complexes and translational machinery that assemble under stressful conditions. Sodium selenite (Se) induces the assembly of noncanonical type II SGs that differ in morphology, composition, and mechanism of assembly from canonical SGs. Se inhibits translation initiation by altering the cap-binding activity of eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1). In this work, we show that human immunodeficiency virus type 1 (HIV-1) Gag is able to block the assembly of type II noncanonical SGs to facilitate continued Gag protein synthesis. We demonstrate that expression of Gag reduces the amount of hypophosphorylated 4EBP1 associated with the 5′ cap potentially through an interaction with its target, eIF4E. These results suggest that the assembly of SGs is an important host antiviral defense that HIV-1 has evolved for inhibition through several distinct mechanisms. IMPORTANCE The antiviral stress response is an important host defense that many viruses, including HIV-1, have evolved to evade. Selenite induces a block in translation and leads to stress granule assembly through the sequestration of eIF4E by binding hypophosphorylated 4EBP1. In this work, we demonstrate that in the face of selenite-induced stress, HIV-1 is able to maintain Gag mRNA translation and to elicit a blockade to selenite-induced stress granule assembly by altering the amount of hypophosphorylated 4EBP1 on the 5′ cap. The antiviral stress response is an important host defense that many viruses, including HIV-1, have evolved to evade. Selenite induces a block in translation and leads to stress granule assembly through the sequestration of eIF4E by binding hypophosphorylated 4EBP1. In this work, we demonstrate that in the face of selenite-induced stress, HIV-1 is able to maintain Gag mRNA translation and to elicit a blockade to selenite-induced stress granule assembly by altering the amount of hypophosphorylated 4EBP1 on the 5′ cap.

This work sheds light on the role of the lipid 1-tuberculosinyladenosine in the evolution of an environmental ancestor to M. tuberculosis . On a larger scale, it reinforces the importance of horizontal gene transfer in bacterial evolution and examines novel models and methods to provide a better understanding of the subtle effects of individual M. tuberculosis -specific virulence factors in infection settings that are relevant to the pathogen. Mycobacterium kansasii is an environmental nontuberculous mycobacterium that causes opportunistic tuberculosis-like disease. It is one of the most closely related species to the Mycobacterium tuberculosis complex. Using M. kansasii as a proxy for the M. kansasii - M. tuberculosis common ancestor, we asked whether introducing the M. tuberculosis -specific gene pair Rv3377c-Rv3378c into M. kansasii affects the course of experimental infection. Expression of these genes resulted in the production of an adenosine-linked lipid species, known as 1-tuberculosinyladenosine (1-TbAd), but did not alter growth in vitro under standard conditions. Production of 1-TbAd enhanced growth of M. kansasii under acidic conditions through a bacterial cell-intrinsic mechanism independent of controlling pH in the bulk extracellular and intracellular spaces. Production of 1-TbAd led to greater burden of M. kansasii in the lungs of C57BL/6 mice during the first 24 h after infection, and ex vivo infections of alveolar macrophages recapitulated this phenotype within the same time frame. However, in long-term infections, production of 1-TbAd resulted in impaired bacterial survival in both C57BL/6 mice and Ccr2 −/− mice. We have demonstrated that M. kansasii is a valid surrogate of M. tuberculosis to study virulence factors acquired by the latter organism, yet shown the challenge inherent to studying the complex evolution of mycobacterial pathogenicity with isolated gene complementation. IMPORTANCE This work sheds light on the role of the lipid 1-tuberculosinyladenosine in the evolution of an environmental ancestor to M. tuberculosis . On a larger scale, it reinforces the importance of horizontal gene transfer in bacterial evolution and examines novel models and methods to provide a better understanding of the subtle effects of individual M. tuberculosis -specific virulence factors in infection settings that are relevant to the pathogen.

This work reports, for the first time, the mineralogical and geochemical characteristics of karst aquifers in the Central West Bank (CWB) catchment in Palestine. It provides an integrated study approach by correlating the geochemistry of the lithology and hydrochemical data of groundwater samples. Mineralogical analysis showed that all of the samples were dominantly composed of either calcite CaCO3 (5–100 wt. %) or dolomite CaMg(CO3)2 (4–100 wt. %), with minor amounts of quartz and feldspar, which is supported by the inorganic carbon content (9–13 wt. %) and hydrochemical composition of the spring water samples. The whole-rock geochemical data indicated that the samples have low contents of trace elements and transition metals. In contrast, the concentrations of alkaline earth elements (Mg, Ca, Sr, Ba) and Mn were high in the rock and groundwater samples. Generally, the trace elements of rock samples with concentrations >10 ppm included Sr (17–330 ppm), Mn (17–367 ppm), Ba (2–32 ppm), W (5–37 ppm), Cr (3–23 ppm), Zn (1.7–28 ppm), V (4–23 ppm), and Zr (1–22 ppm), while the concentrations of all the other trace elements was below 10 ppm. Ionic ratios and hierarchical cluster analysis (HCA) suggested that the chemical evolution of groundwater was mainly related to the geogenic (rock–water) interaction in the study area. This is clear in the alkaline earth elements (Mg, Ca, Sr, Ba) ratios, especially regarding the Sr values. The calcite rock samples had higher Sr (mean 160 ppm, n = 11) than those of the dolomite rocks (mean 76 ppm, n = 9).

Las Loras UNESCO Global Geopark (UGGp) is geologically diverse, particularly in relation to water-derived features: springs, karst springs, travertine buildings, waterfalls, caves. In this work, the interactions between geology, geomorphology, structures and hydrogeology are analyzed. As a result of this study, a first conceptual model of the hydrogeological functioning at Las Loras UGGp is presented. The most plausible hypothesis is that the system is formed by two superimposed aquifer systems, separated by an aquitard formed by Lower Cretaceous material. The deep lower aquifer formed by the Jurassic limestones only outcrops on the northern and southern edges of the Geopark and in a small arched band to the south of Aguilar de Campoo. It forms a basement subject to intense deformation. The upper aquifer system, formed by outcropping materials from the Upper Cretaceous, is a free aquifer. It is formed by a multilayered aquifer system that is highly compartmentalized, constituting individual moorland and lora units acting as a separate recharge–discharge system. This model explains the base level of the permanent rivers and the abundant springs, important components of the water cycle and representing a contribution to the rich geological heritage of the location.

The objective of this study is to investigate the hydrogeological and hydrochemical characteristics of the spring aquifer system in the potential Jericho Geopark in Jericho, Palestine. The spring’s hydrochemistry influences the physical and hydrochemical characteristics of Jericho Geopark in qualitative potentials. The springs are used for domestic water supplies and irrigation in Jericho area, which is considered as one of the most important agricultural baskets of the West Bank feeding from the “spring system complex”. From the geological and structural point of view, the area is considered to be complex in relation to the major structural features of faults and folds, which formed during the formation of the Jordan Rift Valley. The physical properties (pH, DO, temperature, TDS and EC) were interpreted. The hydro-chemical concentration major ions of Ca2+, Mg2+, Na+, K+, Cl−, SO42−, NO3− and HCO3− were analyzed for the spring water system samples. The dominant spring water type is the calcium bicarbonate due to the dissociation of calcite mineral during the water rock interaction processes. The microbiological parameters of Total and Fecal coliforms were analyzed for the targeted springs and indicates no detected pollution. The hydrochemical characteristics of the spring waters indicate no ion concentration trends. The calculated quality water Index indicated that all springs are of excellent spring water type. The study contributes to the qualitative spring water as a major component to the potential Jericho Geopark in order to have better understanding of the community-based protection practice.

Drug-resistant tuberculosis (TB) is estimated to cause 13% of all antimicrobial resistance-attributable deaths worldwide and is driven by both ongoing resistance acquisition and person-to-person transmission. Poor outcomes are exacerbated by late diagnosis and inadequate access to effective treatment. Advances in rapid molecular testing have recently improved the diagnosis of TB and drug resistance. Next-generation sequencing of Mycobacterium tuberculosis has increased our understanding of genetic resistance mechanisms and can now detect mutations associated with resistance phenotypes. All-oral, shorter drug regimens that can achieve high cure rates of drug-resistant TB within 6–9 months are now available and recommended but have yet to be scaled to global clinical use. Promising regimens for the prevention of drug-resistant TB among high-risk contacts are supported by early clinical trial data but final results are pending. A person-centred approach is crucial in managing drug-resistant TB to reduce the risk of poor treatment outcomes, side effects, stigma and mental health burden associated with the diagnosis. In this Review, we describe current surveillance of drug-resistant TB and the causes, risk factors and determinants of drug resistance as well as the stigma and mental health considerations associated with it. We discuss recent advances in diagnostics and drug-susceptibility testing and outline the progress in developing better treatment and preventive therapies.In this Review, Pai and colleagues examine the global landscape of drug-resistant tuberculosis, exploring its epidemiology, causes, risk factors, stigma and associated mental health burden as well as discussing the most recent developments in diagnostics, treatment and preventive regimens.

Watershed modelling was carried out in Sarida Catchment in the West Bank (Palestine) in order to determine the physical characteristics of the watershed. Generated storm water and runoff were estimated for watershed sub-catchments for enhancing the potentiality of rainwater harvesting development. Climatic data across eight years (seven wet seasons) were used for watershed modelling by using the software application systems of Watershed Modelling and Hydrologic Modelling. The Geographical Information System (GIS) and Microsoft Excel were used as well for the estimation of different model parameters and features. The physical and meteorological characteristics for each sub-catchment including land use, topography, soil, rainfall, and other parameters were identified. The model results provided sensitive conceptual principles for understanding the runoff mechanisms in the watershed. The average generated storm water over the seven seasons (2008/09 to 2014/15) is 23.16 and 13.44 Mm 3 /year for northern and southern sub-catchments in Sarida watershed, respectively. The generated runoff of the sub-catchments over this period ranged between 2.13 and 23.18 million cubic meters per year. The results suggest a high potential for rainwater harvesting to promote agricultural development and the need to establish a climatic monitoring network in Sarida watershed, as well as in other catchments in the West Bank, for better informing watershed management practices and policies.