Discovery of Conformationally Constrained Dihydro Benzo-Indole Derivatives as Metallo-β-Lactamase Inhibitors to Tackle Multidrug-Resistant Bacterial Infections.

The discovery of metallo-β-lactamase (MBL) inhibitors is crucial in the fight against bacterial infections following the emergence and rapid spread of New Delhi metallo-β-lactamase-1 (NDM-1), as well as clinically relevant Verona integrin-encoded metallo-β-lactamase (VIM), and Imipenemase (IMP). The situation is alarming as there are insufficient antibiotics in the pipeline to combat critical multidrug-resistant infections. Here, we report the discovery of novel dihydrobenzo-indole (dBI) derivatives as a new class of potent metallo-β-lactamase inhibitors (MBLIs) by applying scaffold hopping, conformation constrained, and substituent-decorating strategies.

Temporal Dynamics of Microbial Community Composition and Antimicrobial Resistance in a Mass Gathering Setting Using Culturomics and Metagenomic Approaches.

Introduction: Antimicrobial resistance (AMR) is one of the major global concerns in the current scenario. Mass-gathering events in fast-developing and densely populated areas may contribute to antibiotic resistance. Despite meticulous planning and infrastructure development, the effect of mass gatherings on microbial ecosystems and antibiotic resistance must be investigated.

alginate lyase and Psl glycoside hydrolase inhibit biofilm formation by CF2843 on three-dimensional aggregates of lung epithelial cells.

is an opportunistic pathogen that produces a biofilm containing the polysaccharides, alginate, Psl, and Pel, and causes chronic lung infection in cystic fibrosis patients. Others and we have previously explored the use of alginate lyases in inhibiting biofilm formation on plastic and lung epithelial cell monolayers. We now employ a more physiologically representative model system, i.

SAXS data based glycosylated models of human alpha-1-acid glycorprotein, a key player in health, disease and drug circulation.

Plasma Alpha-1-glycoprotein (AGP) binds diverse drugs, its isoforms and their levels vary significantly in acute phases of health. Relative binding pattern of drugs to AGP and albumin has been used to model their release profiles, and structural insights on glycosylated form of AGP will improve predictions. Main challenge is the heavy and heterogeneous glycosylation of AGP molecules.

Genomic insights into Marinospirillum alkalitolerans sp. nov., a novel PHB producing bacterium from an Indian impact crater, and an emended description of family Oceanospirillaceae.

Two Gram-stain-negative bacterial strains (MEB164 and MEB148), were isolated from haloalkaline waters of Lonar, crater lake, India. The strains were helical, non-spore-forming and motile with polar tufts of flagella. Optimal growth occurred at 37 ℃, at pH 10 and with 3% (w/v) NaCl.

Comprehensive safety and toxicity analysis of 2,2'-Bipyridine derivatives in combating MRSA biofilm formation and persistence.

Introduction: Methicillin-resistant (MRSA) infections have become arduous to treat due to their capacity to form biofilms, develop persistence, and exhibit significant antimicrobial resistance. These factors contribute to the complexity of managing MRSA infections and highlight the urgent need for innovative treatment strategies.

Objectives: This endeavor aims to evaluate the safety of 2,2'-Bipyridine (2,2'-Bipy) derivatives and their antimicrobial, anti-biofilm, and anti-persister activities in treating MRSA Infections.

Burkholderia cepacia complex nosocomial outbreaks in India: A scoping review.

Burkholderia cepacia complex (Bcc) is an opportunistic pathogen that causes severe infections in immunocompromised individuals. It is a common contaminant of medical drugs, solutions and devices used in healthcare setups. This scoping review aimed to assess Bcc outbreaks in Indian hospital settings and address a wide range of sources to improve outbreak management.

The Microbiology Galaxy Lab: A community-driven gateway to tools, workflows, and training for reproducible and FAIR analysis of microbial data.

Microbial research generates vast and complex data from diverse omics technologies, demanding innovative analytical solutions. The microGalaxy community addresses these needs with the Microbiology Lab, a user-friendly platform that integrates 290+ tool suites and 85+ curated workflows for microbial analyses, including taxonomic profiling, assembly, annotation, and functional analysis. Hosted on several public Galaxy servers (microbiology.

Bioremediation of catecholic pollutants with novel oxygen-insensitive catechol 2,3-dioxygenase and its potential in biomonitoring of catechol in wastewater.

The oxygenases are essential in the bioremediation of xenobiotic pollutants. To overcome cultivability constraints, this study aims to identify new potential extradiol dioxygenases using the functional metagenomics approach. RW1-4CC, a novel catechol 2,3-dioxygenase, was isolated using functional metagenomics approach, expressed in a heterologous system, and characterized thoroughly using state-of-the-art techniques.

Palladium-Catalyzed Intramolecular C-H Amination via Oxidative Coupling on Indole Derivatives: Access to 11-Benzo[4,5]imidazo[1,2-]indoles.

A novel palladium-catalyzed intramolecular C-H amination via oxidative coupling exploiting inactivated N-substituted aryl amines on indoles for the one-pot synthesis of novel 11-benzo[4,5]imidazo[1,2-]indole derivatives is reported. The optimized reaction conditions accommodated a wide range of electronic variations on both the indole and the pendant aryl amine ring, resulting in products with good to excellent yields.

Biochemical and molecular mechanisms of Rhodococcus rhodochrous IITR131 for polyethylene terephthalate degradation.

Aims: To isolate polyethylene terephthalate (PET)-degrading bacteria and elucidate the underlying mechanisms of PET biodegradation through biochemical and genome analysis.

Methods And Results: Rhodococcus rhodochrous IITR131 was found to degrade PET. Strain IITR131 genome revealed metabolic versatility of the bacterium and had the ability to form biofilm on PET sheet, resulting in the cracks, abrasions, and degradation.

Tubules, Rods, and Spirals: Diverse Modes of SepF-FtsZ Assembling.

Z-ring formation by FtsZ, the master assembler of the divisome, is a key step in bacterial cell division. Membrane anchoring of the Z-ring requires the assistance of dedicated Z-ring binding proteins, such as SepF and FtsA. SepF participates in bundling and membrane anchoring of FtsZ in gram-positive bacteria.

Anticandidal Efficacy of Green Synthesized Silver Nanoparticles Using Trans-Himalayan Plant Extracts Against Drug Resistant Clinical Isolates of .

Unlabelled: is the most common, globally detected nosocomial fungal pathogen with multi-drug resistance. The high prevalence of infections has raised concern about drug resistance and adverse effects, compounded by a lack of effective alternative drugs. Bioengineered nanomaterials play a significant role in combating nosocomial infections.

Substitution of leucine by glutamate perturbs VopE localization to mitochondria: Lessons from yeast model system.

VopE, a type III effector protein of Vibrio cholerae, modulates host mitochondrial function. Mitochondrial entry of VopE is directly linked with an N-terminal precursor sequence known as the mitochondrial targeting sequence or MTS. MTS of VopE is constituted with 23 amino acids.

Visualizing gaussian-chain like structural models of human α-synuclein in monomeric pre-fibrillar state: Solution SAXS data and modeling analysis.

Here, using small angle X-ray scattering (SAXS) data profile as reference, we attempted to visualize conformational ensemble accessible prefibrillar monomeric state of α-synuclein in solution. In agreement with previous reports, our analysis also confirmed that α-synuclein molecules adopted disordered shape profile under non-associating conditions. Chain-ensemble modeling protocol with dummy residues provided two weighted averaged clusters of semi-extended shapes.

Administration of novobiocin and apomorphine mitigates cholera toxin mediated cellular toxicity: Lessons from cholera toxin yeast model system.

Cholera is a dreadful disease. The scourge of this deadly disease is still evident in the developing world. Though several therapeutic strategies are in practice to combat and contain the disease, there is still a need for new drugs to control the disease safely and effectively.

Oleuropein: a viable therapeutic option for malaria and cancer.

Oleuropein (OLP) holds promise as a therapeutic candidate for both Plasmodium falciparum infection and cancer. It modulates the phosphoinositide 3-kinase (PI3K)-Akt1 signaling pathway to regulate inflammation and restore immune homeostasis. Moreover, it influences the cell death/autophagy axis, along with increasing the antimalarial efficacy of artemisinin.

HiFiBGC: an ensemble approach for improved biosynthetic gene cluster detection in PacBio HiFi-read metagenomes.

Background: Microbes produce diverse bioactive natural products with applications in fields such as medicine and agriculture. In their genomes, these natural products are encoded by physically clustered genes known as biosynthetic gene clusters (BGCs). Genome and metagenome sequencing advances have enabled high-throughput identification of BGCs as a promising avenue for natural product discovery.

2,2'- Bipyridine Derivatives Exert Anticancer Effects by Inducing Apoptosis in Hepatocellular Carcinoma (HepG2) Cells.

Purpose: To elucidate the therapeutic potential of 2,2'-bipyridine derivatives [NPS (1-6)] on hepatocellular carcinoma HepG2 cells.

Methods: The effects on cell survival, colony formation, cellular and nuclear morphology, generation of reactive oxygen species (ROS), change in the integrity of mitochondrial membrane potential (MMP), and apoptosis were investigated. Additionally, docking studies were conducted to analyze and elucidate the interactions between the derivatives and AKT and BRAF proteins.

Synthetic indole derivatives as an antibacterial agent inhibiting respiratory metabolism of multidrug-resistant gram-positive bacteria.

The survival of modern medicine depends heavily on the effective prevention and treatment of bacterial infections, are threatened by antibacterial resistance. The increasing use of antibiotics and lack of stewardship have led to an increase in antibiotic-resistant pathogens, so the growing issue of resistance can be resolved by emphasizing chemically synthesized antibiotics. This study discovered SMJ-2, a synthetic indole derivative, is effective against all multidrug-resistant gram-positive bacteria.

Rho and riboswitch-dependent regulations of mntP gene expression evade manganese and membrane toxicities.

The trace metal ion manganese (Mn) in excess is toxic. Therefore, a small subset of factors tightly maintains its cellular level, among which an efflux protein MntP is the champion. Multiple transcriptional regulators and a manganese-dependent translational riboswitch regulate the MntP expression in Escherichia coli.

Modulation of gut microbiome in response to the combination of Nissle 1917 and sugars: a pilot study using host-free system reflecting impact on interpersonal microbiome.

Introduction: The differential effects of probiotic, prebiotic, and synbiotic formulations on human health are dictated by the inter-individual gut microbial profile. The effects of probiotics such as Nissle 1917 (ECN) on gut microbiota may vary according to the microbiome profiles of individuals and may be influenced by the presence of certain carbohydrates, which can impact microbial community structure and treatment results.

Method: Processed fecal samples from donors having contrasting lifestyles, dietary patterns, and disease histories were mixed with 5 × 10 CFU/mL ECN with or without 1% (w/v) sugars (glucose, galactose, or rice starch) in a host-free system.

Xanthomonas protegens sp. nov., a novel rice seed-associated bacterium, provides in vivo protection against X. oryzae pv. oryzae, the bacterial leaf blight pathogen.

Historically, Xanthomonas species are primarily known for their pathogenicity against plants, but recently, there have been more findings of non-pathogenic xanthomonads. In the present study, we report isolates from healthy rice seeds that belong to a new species, Xanthomonas protegens, a protector of the rice plants against a serious pathogenic counterpart, i.e.

Mycobacterium tuberculosis exploits SIRT2 to trap iron for its intracellular survival.

Iron is a critical nutrient for all organisms ranging from bacteria to humans. Ensuring control of this strategic vital resource significantly influences the dynamics of the struggle between host and invading pathogen. Mycobacterium tuberculosis (Mtb), the causative agent of the pulmonary disease tuberculosis (TB), has been plaguing humans for millennia and has evolved to successfully persist and multiply within host cells evading the mammalian immune defences.