Sugar phosphate-mediated inhibition of peptidoglycan precursor synthesis.

Antibiotic tolerance, the widespread ability of diverse pathogenic bacteria to sustain viability in the presence of typically bactericidal antibiotics for extended time periods, is an understudied steppingstone towards antibiotic resistance. The Gram-negative pathogen , the causative agent of cholera, is highly tolerant to β-lactam antibiotics. We previously found that the disruption of glycolysis, via deletion of (, glucose-6-phosphate isomerase), resulted in significant cell wall damage and increased sensitivity towards β-lactam antibiotics.

Estimating black carbon levels using machine learning models in high-concentration regions.

Black carbon (BC) is emitted into the atmosphere during combustion processes, often in conjunction with emissions such as nitrogen oxides (NO) and ozone (O), which are also by-products of combustion. In highly polluted regions, combustion processes are one of the main sources of aerosols and particulate matter (PM) concentrations, which affect the radiative budget. Despite the high relevance of this air pollution metric, BC monitoring is quite expensive in terms of instrumentation and of maintenance and servicing.

The operon protects magnesium-dependent enzymes by supporting manganese efflux.

Microbes encounter a myriad of stresses during their life cycle. Dysregulation of metal ion homeostasis is increasingly recognized as a key factor in host-microbe interactions. Bacterial metal ion homeostasis is tightly regulated by dedicated metalloregulators that control uptake, sequestration, trafficking, and efflux.

The operon protects magnesium-dependent enzymes by supporting manganese efflux.

Microbes encounter a myriad of stresses during their life cycle. Dysregulation of metal ion homeostasis is increasingly recognized as a key factor in host-microbe interactions. Bacterial metal ion homeostasis is tightly regulated by dedicated metalloregulators that control uptake, sequestration, trafficking, and efflux.

Metabolic Rewiring of upon Drug Treatment and Antibiotics Resistance.

Tuberculosis (TB), caused by (), remains a significant global health challenge, further compounded by the issue of antimicrobial resistance (AMR). AMR is a result of several system-level molecular rearrangements enabling bacteria to evolve with better survival capacities: metabolic rewiring is one of them. In this review, we present a detailed analysis of the metabolic rewiring of in response to anti-TB drugs and elucidate the dynamic mechanisms of bacterial metabolism contributing to drug efficacy and resistance.

, a Promising Vaccine Vector for Preventing TB and Other Diseases: Vaccinomics Insights and Applications.

() is frequently used as an alternative model organism in ) studies. While containing high sequence homology with it is considered non-pathogenic in humans. As such it has been used to study and other infections in vivo and more recently been explored for potential therapeutic applications.

Insights into the central role of N-acetyl-glucosamine-1-phosphate uridyltransferase (GlmU) in peptidoglycan metabolism and its potential as a therapeutic target.

Several decades after the discovery of the first antibiotic (penicillin) microbes have evolved novel mechanisms of resistance; endangering not only our abilities to combat future bacterial pandemics but many other clinical challenges such as acquired infections during surgeries. Antimicrobial resistance (AMR) is attributed to the mismanagement and overuse of these medications and is complicated by a slower rate of the discovery of novel drugs and targets. Bacterial peptidoglycan (PG), a three-dimensional mesh of glycan units, is the foundation of the cell wall that protects bacteria against environmental insults.

Mutations in That Confer Rifampicin Resistance Can Alter Levels of Peptidoglycan Precursors and Affect β-Lactam Susceptibility.

Bacteria can adapt to stressful conditions through mutations affecting the RNA polymerase core subunits that lead to beneficial changes in transcription. In response to selection with rifampicin (RIF), mutations arise in the RIF resistance-determining region (RRDR) of that reduce antibiotic binding. These changes can also alter transcription and thereby have pleiotropic effects on bacterial fitness.

Therapeutic Potentials of Immunometabolomic Modulations Induced by Tuberculosis Vaccination.

Metabolomics is emerging as a promising tool to understand the effect of immunometabolism for the development of novel host-directed alternative therapies. Immunometabolism can modulate both innate and adaptive immunity in response to pathogens and vaccinations. For instance, infections can affect lipid and amino acid metabolism while vaccines can trigger bile acid and carbohydrate pathways.

Immunotherapy: an alternative promising therapeutic approach against cancers.

The immune system interacts with cancer cells in multiple intricate ways that can shield the host against hyper-proliferation but can also contribute to malignancy. Understanding the protective roles of the immune system in its interaction with cancer cells can help device new and alternate therapeutic strategies. Many immunotherapeutic methodologies, including adaptive cancer therapy, cancer peptide vaccines, monoclonal antibodies, and immune checkpoint treatment, have transformed the traditional cancer treatment landscape.

B-Cell-Based Immunotherapy: A Promising New Alternative.

The field of immunotherapy has undergone radical conceptual changes over the last decade. There are various examples of immunotherapy, including the use of monoclonal antibodies, cancer vaccines, tumor-infecting viruses, cytokines, adjuvants, and autologous T cells carrying chimeric antigen receptors (CARs) that can bind cancer-specific antigens known as adoptive immunotherapy. While a lot has been achieved in the field of T-cell immunotherapy, only a fraction of patients (20%) see lasting benefits from this mode of treatment, which is why there is a critical need to turn our attention to other immune cells.

A critical review of the application of polymer of low concern regulatory criteria to fluoropolymers II: Fluoroplastics and fluoroelastomers.

Fluoropolymers are a distinct class of per- and polyfluoroalkyl substances (PFAS), high molecular weight (MW) polymers with fluorine attached to their carbon-only backbone. Fluoropolymers possess a unique combination of properties and unmatched functional performance critical to the products and manufacturing processes they enable and are irreplaceable in many uses. Fluoropolymers have documented safety profiles; are thermally, biologically, and chemically stable, negligibly soluble in water, nonmobile, nonbioavailable, nonbioaccumulative, and nontoxic.

A hydrogel-based implantable multidrug antitubercular formulation outperforms oral delivery.

We present a non-immunogenic, injectable, low molecular weight, amphiphilic hydrogel-based drug delivery system (TB-Gel) that can entrap a cocktail of four front-line antitubercular drugs, isoniazid, rifampicin, pyrazinamide, and ethambutol. We showed that TB-Gel is more effective than oral delivery of the combination of four drugs in reducing the mycobacterial infection in mice. Results show that half the dose of chemotherapeutic drugs is sufficient to achieve a comparable therapeutic effect to that of oral delivery.

Signature of strong localization and crossover conduction processes in doped ZnO thin films: synergetic effect of doping fraction and dense electronic excitations.

GaZnO thin films with varying Ga fraction within the solubility limit were irradiated with high-energy heavy ions to induce electronic excitations. The films show good transmittance in the visible region and a reduction of about 20% in transmittance was observed for irradiated films at higher ion fluences. The Urbach energy was estimated and showed an augmenting response upon increase in doping fraction and ion irradiation, this divulges an enhancement of localized states in the bandgap or disorder in the films.

Unique C-terminal extension and interactome of Mycobacterium tuberculosis GlmU impacts it's in vivo function and the survival of pathogen.

N-acetyl glucosamine-1-phosphate uridyltransferase (GlmU) is a bifunctional enzyme involved in the biosynthesis of Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is a critical precursor for the synthesis of peptidoglycan and other cell wall components. The absence of a homolog in eukaryotes makes GlmU an attractive target for therapeutic intervention.

Improved air quality during COVID-19 at an urban megacity over the Indo-Gangetic Basin: From stringent to relaxed lockdown phases.

The enforced lockdown amid COVID-19 pandemic eased anthropogenic activities across India. The satellite-derived aerosol optical depth (AOD) and absorption AOD showed a significant reduction of ~30% over the Indo-Gangetic Basin (IGB) in north India during the lockdown period in 2020 with respect to the previous year 2019, when no such lockdown was in effect. Further, near-surface air pollutants were investigated at an urban megacity Delhi during 01 March to 31 May 2020.

Performance of high resolution (400 m) PM forecast over Delhi.

This study reports a very high-resolution (400 m grid-spacing) operational air quality forecasting system developed to alert residents of Delhi and the National Capital Region (NCR) about forthcoming acute air pollution episodes. Such a high-resolution system has been developed for the first time and is evaluated during October 2019-February 2020. The system assimilates near real-time aerosol observations from in situ and space-borne platform in the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) to produce a 72-h forecast daily in a dynamical downscaling framework.

Transcriptional regulator-induced phenotype screen reveals drug potentiators in Mycobacterium tuberculosis.

Transposon-based strategies provide a powerful and unbiased way to study the bacterial stress response, but these approaches cannot fully capture the complexities of network-based behaviour. Here, we present a network-based genetic screening approach: the transcriptional regulator-induced phenotype (TRIP) screen, which we used to identify previously uncharacterized network adaptations of Mycobacterium tuberculosis to the first-line anti-tuberculosis drug isoniazid (INH). We found regulators that alter INH susceptibility when induced, several of which could not be identified by standard gene disruption approaches.

Evaluation of spatial and temporal heterogeneity of black carbon aerosol mass concentration over India using three year measurements from IMD BC observation network.

Extensive measurements of equivalent black carbon (EBC) aerosol mass concentration at fifteen stations of India Meteorological Department (IMD) BC observation network during the period 2016-2018 are used to study the spatial and temporal heterogeneity over India. The sampling sites represent different geographical region of India. Spatial distribution shows higher values of EBC over stations of north India and IGP.

Mode-of-action profiling reveals glutamine synthetase as a collateral metabolic vulnerability of to bedaquiline.

Combination chemotherapy can increase treatment efficacy and suppress drug resistance. Knowledge of how to engineer rational, mechanism-based drug combinations, however, remains lacking. Although studies of drug activity have historically focused on the primary drug-target interaction, growing evidence has emphasized the importance of the subsequent consequences of this interaction.

The bifunctional protein GlmU is a key factor in biofilm formation induced by alkylating stress in Mycobacterium smegmatis.

Living organisms have developed specific defence mechanisms to counteract hostile environmental conditions. Alkylation stress response mechanisms also occur in Mycobacterium tuberculosis (MTB) the pathogen responsible for tuberculosis. The effect of alkylating agents on the cellular growth of MTB was investigated using methyl methanesulfonate (MMS) as methyl donor demonstrating that limited doses of alkylating agents might affect MTB cell viability.