Sideromycins are a group of antibiotics linked to siderophores by covalent bonds. Examples of naturally occurring sideromycins are albomycin and salmycin. [1] Sideromycins have some unique merits as antibiotic. They can actively bypass permeability barriers (membranes) to deliver the drug inside the target bacterial cell, irrespective of the size and polarity of the antibiotic moiety contained into it. Most importantly as they are substrates of high affinity siderophore transport systems they can be effective to kill bacteria at very low concentration. Also the delivery of the antibiotic will be highly target specific, so wouldn't affect the host system. Sideromycins is being considered as a new microbe-selective antibacterial agent, which can limit the emergence of resistance. [2]
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit growth of viruses are termed antiviral drugs or antivirals rather than antibiotics. They are also not effective against fungi; drugs which inhibit growth of fungi are called antifungal drugs.
The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system where neurons reside. The blood–brain barrier is formed by endothelial cells of the capillary wall, astrocyte end-feet ensheathing the capillary, and pericytes embedded in the capillary basement membrane. This system allows the passage of some small molecules by passive diffusion, as well as the selective and active transport of various nutrients, ions, organic anions, and macromolecules such as glucose and amino acids that are crucial to neural function.
Pseudomonas fluorescens is a common Gram-negative, rod-shaped bacterium. It belongs to the Pseudomonas genus; 16S rRNA analysis as well as phylogenomic analysis has placed P. fluorescens in the P. fluorescens group within the genus, to which it lends its name.
Siderophores (Greek: "iron carrier") are small, high-affinity iron-chelating compounds that are secreted by microorganisms such as bacteria and fungi. They help the organism accumulate iron. Although a widening range of siderophore functions is now being appreciated. Siderophores are among the strongest (highest affinity) Fe3+ binding agents known. Phytosiderophores are siderophores produced by plants.
Aspergillus fumigatus is a species of fungus in the genus Aspergillus, and is one of the most common Aspergillus species to cause disease in individuals with an immunodeficiency.
In chemistry, an ionophore is a chemical species that reversibly binds ions. Many ionophores are lipid-soluble entities that transport ions across the cell membrane. Ionophores catalyze ion transport across hydrophobic membranes, such as liquid polymeric membranes or lipid bilayers found in the living cells or synthetic vesicles (liposomes). Structurally, an ionophore contains a hydrophilic center and a hydrophobic portion that interacts with the membrane.
Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for antimicrobial peptides. These peptides are potent, broad spectrum antibiotics which demonstrate potential as novel therapeutic agents. Antimicrobial peptides have been demonstrated to kill Gram negative and Gram positive bacteria, enveloped viruses, fungi and even transformed or cancerous cells. Unlike the majority of conventional antibiotics it appears that antimicrobial peptides frequently destabilize biological membranes, can form transmembrane channels, and may also have the ability to enhance immunity by functioning as immunomodulators.
Pseudomonas aeruginosa is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, P. aeruginosa is a multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistance mechanisms, and its association with serious illnesses – hospital-acquired infections such as ventilator-associated pneumonia and various sepsis syndromes.
Cheating is a term used in behavioral ecology and ethology to describe behavior whereby organisms receive a benefit at the cost of other organisms. Cheating is common in many mutualistic and altruistic relationships. A cheater is an individual who does not cooperate but can potentially gain the benefit from others cooperating. Cheaters are also those who selfishly use common resources to maximize their individual fitness at the expense of a group. Natural selection favors cheating, but there are mechanisms to regulate it. The stress gradient hypothesis states that facilitation, cooperation or mutualism should be more common in stressful environments, while cheating, competition or parasitms are common in benign environments.
Monobactams are monocyclic and bacterially-produced β-lactam antibiotics. The β-lactam ring is not fused to another ring, in contrast to most other β-lactams. Monobactams are effective only against aerobic Gram-negative bacteria. Siderophore-conjugated monobactams show promise for the treatment of multi drug-resistant pathogens.
Burkholderia cenocepacia is a Gram-negative, rod-shaped bacterium that is commonly found in soil and water environments and may also be associated with plants and animals, particularly as a human pathogen. It is one of over 20 species in the Burkholderia cepacia complex (Bcc) and is notable due to its virulence factors and inherent antibiotic resistance that render it a prominent opportunistic pathogen responsible for life-threatening, nosocomial infections in immunocompromised patients, such as those with cystic fibrosis or chronic granulomatous disease. The quorum sensing systems CepIR and CciIR regulate the formation of biofilms and the expression of virulence factors such as siderophores and proteases. Burkholderia cenocepacia may also cause disease in plants, such as in onions and bananas. Additionally, some strains serve as plant growth-promoting rhizobacteria.
Cobalamin riboswitch is a cis-regulatory element which is widely distributed in 5' untranslated regions of vitamin B12 (Cobalamin) related genes in bacteria.
Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and are often beneficial but others can cause infectious diseases. The number of these pathogenic species in humans is estimated to be fewer than a hundred. By contrast, several thousand species are part of the gut flora present in the digestive tract.
Ferrichrome is a cyclic hexa-peptide that forms a complex with iron atoms. It is a siderophore composed of three glycine and three modified ornithine residues with hydroxamate groups [-N(OH)C(=O)C-]. The 6 oxygen atoms from the three hydroxamate groups bind Fe(III) in near perfect octahedral coordination.
Binding selectivity is defined with respect to the binding of ligands to a substrate forming a complex. Binding selectivity describes how a ligand may bind more preferentially to one receptor than another. A selectivity coefficient is the equilibrium constant for the reaction of displacement by one ligand of another ligand in a complex with the substrate. Binding selectivity is of major importance in biochemistry and in chemical separation processes.
Plasmid-mediated resistance is the transfer of antibiotic resistance genes which are carried on plasmids. Plasmids possess mechanisms that ensure their independent replication as well as those that regulate their replication number and guarantee stable inheritance during cell division. By the conjugation process, they can stimulate lateral transfer between bacteria from various genera and kingdoms. Numerous plasmids contain addiction-inducing systems that are typically based on toxin-antitoxin factors and capable of killing daughter cells that don't inherit the plasmid during cell division. Plasmids often carry multiple antibiotic resistance genes, contributing to the spread of multidrug-resistance (MDR). Antibiotic resistance mediated by MDR plasmids severely limits the treatment options for the infections caused by Gram-negative bacteria, especially family Enterobacteriaceae. The global spread of MDR plasmids has been enhanced by selective pressure from antimicrobial medications used in medical facilities and when raising animals for food.
Albomycins are a group of naturally occurring antibiotics belonging to the class of sideromycins, which are "compounds composed of iron carriers called siderophores linked to antibiotic moieties". They are particularly effective against Gram-negative bacteria of the family Enterobacteriaceae and few Gram-positive bacteria such s Streptococcus pneumoniae, Bacillus subtilis and Staphylococcus aureus. In 2000 a group of scientists from SmithKline Beecham Pharmaceuticals, UK reported that the antibiotic part of albomycin in vitro can inhibit seryl t-RNA synthetase from both eukaryotic and prokaryotic representatives.
Rebecca Abergel is a French inorganic chemist who specializes in the coordination chemistry between lanthanide and actinide complexes. Alongside the effects of heavy element exposure and contamination on different biological systems. Abergel is currently a Faculty Scientist and Heavy Element Chemistry Group Leader at the Chemical Sciences Division of Lawrence Berkeley National Laboratory in Berkeley, California. She is also Assistant Professor of Nuclear Engineering at University of California, Berkeley.
Cefiderocol, sold under the brand name Fetroja among others, is an antibiotic used to treat complicated urinary tract infections when no other options are available. It is indicated for the treatment of multi-drug-resistant Gram-negative bacteria including Pseudomonas aeruginosa. It is given by injection into a vein.
Elizabeth Marie Nolan is an American chemist and Associate Professor at Massachusetts Institute of Technology.