Antibiotic Lethality and Membrane Bioenergetics.

Antibiotic Lethality and Membrane Bioenergetics. Adv Microb Physiol. 2018;73:77-122 Authors: Voskuil MI, Covey CR, Walter ND Abstract A growing body of research suggests bacterial metabolism and membrane bioenergetics affect the lethality of a broad spectrum of antibiotics. Electrochemical gradients spanning energy-transducing membranes are the foundation of the chemiosmotic hypothesis and are essential for life; accordingly, their dysfunction appears to be a critical factor in bacterial death. Proton flux across energy-transducing membranes is central for cellular homeostasis as vectorial proton translocation generates a proton motive force used for ATP synthesis, pH homeostasis, and maintenance of solute gradients. Our recent investigations indicate that maintenance of pH homeostasis is a critical factor in antibiotic killing and suggest an imbalance in proton flux initiates disruptions in chemiosmotic gradients that lead to cell death. The complex and interconnected relationships between electron transport systems, central carbon metabolism, oxidative stress generation, pH homeostasis, and electrochemical gradients provide challenging obstacles to deciphering the roles for each of these processes in antibiotic lethality. In this chapter, we will present evidence for the pH homeostasis hypothesis of antibiotic lethality that bactericidal activity flows from disruption of cellular energetics and loss of chemiosmotic homeostasis. A holistic understanding...
Source: Advances in Microbial Physiology - Category: Microbiology Authors: Tags: Adv Microb Physiol Source Type: research

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Publication date: Available online 13 September 2019Source: Life SciencesAuthor(s): Emiliana Echeverría, Ana Julia Velez Rueda, Maia Cabrera, Ezequiel Juritz, Valeria Burghi, Lucas Fabián, Carlos Davio, Pablo Lorenzano Menna, Natalia Cristina FernándezAbstractAimsG protein-coupled receptor (GPCR) kinases (GRKs) are mainly involved in the desensitization of GPCRs. Among them, GRK2 has been described to be upregulated in many pathological conditions and its crucial role in cardiac hypertrophy, hypertension, and heart failure promoted the search for pharmacological inhibitors of its activity. There have b...
Source: Life Sciences - Category: Biology Source Type: research
Malignant gastrointestinal neuroectodermal tumour is an extremely rare neoplasm that arises in the wall of the small bowel, stomach or large bowel in young-aged and middle-aged adults. Histologically, it is generally characterized by monomorphic cells with clear cytoplasma, S-100 protein expression, and EWSR1 gene translocation. To the best of our knowledge, we describe for the first time, the case of a young woman with a diagnosis of metastatic gastrointestinal neuroectodermal tumour arising from ileum, who had a childhood adrenal neuroblastoma with liver, bone and lymph nodes metastasis, treated with four cycles of chemo...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Case Reports Source Type: research
Authors: Grevel A, Pfanner N, Becker T Abstract Biogenesis and function of mitochondria depend on the import of about 1000 precursor proteins that are produced on cytosolic ribosomes. The translocase of the outer membrane (TOM) forms the entry gate for most proteins. After passage through the TOM channel, dedicated preprotein translocases sort the precursor proteins into the mitochondrial subcompartments. Many proteins have to be assembled into oligomeric membrane-integrated complexes in order to perform their functions. In this review, we discuss a dual role of mitochondrial preprotein translocases in protein tran...
Source: Biological Chemistry - Category: Chemistry Tags: Biol Chem Source Type: research
ConclusionsAfter the PGT-SR treatment, the reciprocal translocation carriers who had previously experienced two or more unfavorable pregnancy outcomes had a low risk of miscarriages and birth defects. The rate of normal live births per pregnancy was higher after PGT-SR treatment.
Source: Journal of Assisted Reproduction and Genetics - Category: Reproduction Medicine Source Type: research
In this study, we reported a 2-(N-Phenylmethylsulfonamido)-N-(2-(phenylthio)phenyl)propanamide (PSTP) compound, PSTP-3,5-Me, as a potential therapeutic agent for osteoporosis. Mouse bone marrow-derived macrophages (BMMs) were differentiated into osteoclasts by receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in the presence of PSTP-3,5-Me. PSTP-3,5-Me inhibited osteoclast differentiation by reduced tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and suppressed the expression of osteoclast marker genes, such as cathepsin K (Ctsk) and TRAP (Acp5). W...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
AbstractIn recent decades, the problem of the constantly increasin level of anthropogenic load on the environment is becoming more and more acute. Some of the most dangerous pollutants entering the environment from industrial emissions are heavy metals. These pollutants are not susceptible to biodegradation over time, which leads to their accumulation in the environment in dangerous concentrations. The purpose of this work is to study the sustainability of cultivated and wild plants of the Poaceae family to aerotechnogenic pollution in the soil. The content of heavy metals in couch grass (Elytrigia repens (L.) Nevski), mea...
Source: Environmental Geochemistry and Health - Category: Environmental Health Source Type: research
Abstract The patients with mantle cell lymphoma (MCL) have translocation t(11;14) associated with cyclin D1 overexpression. We observed that iron (an essential cofactor of dioxygenases including prolyl hydroxylases [PHDs]) depletion by deferoxamine blocked MCL cells' proliferation, increased expression of DNA damage marker γH2AX, induced cell cycle arrest and decreased cyclin D1 level. Treatment of MCL cell lines with dimethyloxalylglycine, which blocks dioxygenases involving PHDs by competing with their substrate 2-oxoglutarate, leads to their decreased proliferation and the decrease of cyclin D1 level. We ...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
In this study, the results showed that dioscin significantly ameliorated Dox-induced cell injury, reduced reactive oxygen species (ROS) level, and suppressed cell apoptosis in alpha mouse liver 12 (AML-12) cells caused by Dox. In vivo, dioscin evidently decreased the levels of alanine transaminase (ALT), aspartate transaminase (AST), malondialdehyde (MDA); increased the levels of superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px); and alleviated liver injury. Mechanism study showed that dioscin remarkably up-regulated the expression levels of silent information regulator 1 (Sirt1) and heme o...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
We have shown that the Shigella spa33 gene, encoding a type 3 secretion system component, gives rise to 5 fragments of various sizes. Among them, three are necessary for type 3 secretion. For the first time, we have shown that Spa33 is implicated in the regulation of secretion and interacts with the gatekeeper protein, MxiC. AbstractShigella invasion and dissemination in intestinal epithelial cells relies on a type 3 secretion system (T3SS), which mediates translocation of virulence proteins into host cells. T3SSs are composed of three major parts: an extracellular needle, a basal body, and a cytoplasmic complex. Three cat...
Source: MicrobiologyOpen - Category: Microbiology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Persistent immune activation in virologically suppressed HIV-1 patients, which may be the consequence of various factors including microbial translocation, is a major cause of comorbidities. We have previously shown that different profiles of immune activation may be distinguished in virological responders. Here, we tested the hypothesis that a particular profile might be the consequence of microbial translocation. To this aim, we measured 64 soluble and cell surface markers of inflammation and CD4+ and CD8+ T-cell, B cell, monocyte, NK cell, and endothelial activation in 140 adults under efficient antiretroviral therapy, ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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