European Chemicals Agency
The European Chemicals Agency is an agency of the European Union which manages the technical and administrative aspects of the implementation of the European Union regulation called Registration, Evaluation and Restriction of Chemicals. ECHA is the driving force among regulatory authorities in implementing the EU's chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and addresses chemicals of concern, it is located in Finland. The agency headed by Executive Director Bjorn Hansen, started working on 1 June 2007; the REACH Regulation requires companies to provide information on the hazards and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most used substances have been registered; the information is technical but gives detail on the impact of each chemical on people and the environment.
This gives European consumers the right to ask retailers whether the goods they buy contain dangerous substances. The Classification and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU; this worldwide system makes it easier for workers and consumers to know the effects of chemicals and how to use products safely because the labels on products are now the same throughout the world. Companies need to notify ECHA of the labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100 000 substances; the information is available on their website. Consumers can check chemicals in the products. Biocidal products include, for example, insect disinfectants used in hospitals; the Biocidal Products Regulation ensures that there is enough information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation; the law on Prior Informed Consent sets guidelines for the import of hazardous chemicals.
Through this mechanism, countries due to receive hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have serious effects on human health and the environment are identified as Substances of Very High Concern 1; these are substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment and do not break down. Other substances considered. Companies manufacturing or importing articles containing these substances in a concentration above 0,1% weight of the article, have legal obligations, they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy. Once a substance has been identified in the EU as being of high concern, it will be added to a list; this list is available on ECHA's website and shows consumers and industry which chemicals are identified as SVHCs.
Substances placed on the Candidate List can move to another list. This means that, after a given date, companies will not be allowed to place the substance on the market or to use it, unless they have been given prior authorisation to do so by ECHA. One of the main aims of this listing process is to phase out SVHCs where possible. In its 2018 substance evaluation progress report, ECHA said chemical companies failed to provide “important safety information” in nearly three quarters of cases checked that year. "The numbers show a similar picture to previous years" the report said. The agency noted that member states need to develop risk management measures to control unsafe commercial use of chemicals in 71% of the substances checked. Executive Director Bjorn Hansen called non-compliance with REACH a "worry". Industry group CEFIC acknowledged the problem; the European Environmental Bureau called for faster enforcement to minimise chemical exposure. European Chemicals Bureau Official website
Beta-lactamases are enzymes produced by bacteria that provide multi-resistance to β-lactam antibiotics such as penicillins, cephalosporins and carbapenems, although carbapenems are resistant to beta-lactamase. Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure; these antibiotics all have a common element in their molecular structure: a four-atom ring known as a β-lactam. Through hydrolysis, the lactamase enzyme breaks the β-lactam ring open, deactivating the molecule's antibacterial properties. Beta-lactam antibiotics are used to treat a broad spectrum of Gram-positive and Gram-negative bacteria. Beta-lactamases produced by Gram-negative organisms are secreted when antibiotics are present in the environment; the structure of a Streptomyces β-lactamase is given by 1BSG. Penicillinase is a specific type of β-lactamase, showing specificity for penicillins, again by hydrolysing the β-lactam ring. Molecular weights of the various penicillinases tend to cluster near 50 kiloDaltons.
Penicillinase was the first β-lactamase to be identified. It was first isolated by Abraham and Chain in 1940 from Gram-negative E. coli before penicillin entered clinical use, but penicillinase production spread to bacteria that did not produce it or produced it only rarely. Penicillinase-resistant beta-lactams such as methicillin were developed, but there is now widespread resistance to these. Among Gram-negative bacteria, the emergence of resistance to expanded-spectrum cephalosporins has been a major concern, it appeared in a limited number of bacterial species that could mutate to hyperproduce their chromosomal class C β-lactamase. A few years resistance appeared in bacterial species not producing AmpC enzymes due to the production of TEM- or SHV-type ESBLs. Characteristically, such resistance has included oxyimino-, but not 7-alpha-methoxy-cephalosporins. Chromosomal-mediated AmpC β-lactamases represent a new threat, since they confer resistance to 7-alpha-methoxy-cephalosporins such as cefoxitin or cefotetan but are not affected by commercially available β-lactamase inhibitors, can, in strains with loss of outer membrane porins, provide resistance to carbapenems.
Members of the family express plasmid-encoded β-lactamases, which confer resistance to penicillins but not to expanded-spectrum cephalosporins. In the mid-1980s, a new group of enzymes, the extended-spectrum β-lactamases, was detected; the prevalence of ESBL-producing bacteria have been increasing in acute care hospitals. ESBLs are beta-lactamases that hydrolyze extended-spectrum cephalosporins with an oxyimino side chain; these cephalosporins include cefotaxime and ceftazidime, as well as the oxyimino-monobactam aztreonam. Thus ESBLs confer multi-resistance to related oxyimino-beta lactams. In typical circumstances, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. A broader set of β-lactam antibiotics are susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have been described; the ESBLs are plasmid encoded. Plasmids responsible for ESBL production carry genes encoding resistance to other drug classes.
Therefore, antibiotic options in the treatment of ESBL-producing organisms are limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. TEM-1 is the most encountered beta-lactamase in Gram-negative bacteria. Up to 90% of ampicillin resistance in E. coli is due to the production of TEM-1. Responsible for the ampicillin and penicillin resistance, seen in H. influenzae and N. gonorrhoeae in increasing numbers. Although TEM-type beta-lactamases are most found in E. coli and K. pneumoniae, they are found in other species of Gram-negative bacteria with increasing frequency. The amino acid substitutions responsible for the extended-spectrum beta lactamase phenotype cluster around the active site of the enzyme and change its configuration, allowing access to oxyimino-beta-lactam substrates.
Opening the active site to beta-lactam substrates typically enhances the susceptibility of the enzyme to β-lactamase inhibitors, such as clavulanic acid. Single amino acid substitutions at positions 104, 164, 238, 240 produce the ESBL phenotype, but ESBLs with the broadest spectrum have more than a single amino acid substitution. Based upon different combinations of changes 140 TEM-type enzymes have been described. TEM-10, TEM-12, TEM-26 are among the most common in the United States; the term TEM comes from the name of the Athenian patient from which the isolate was recovered in 1963. SHV-1 has a similar overall structure; the SHV-1 beta-lactamase is most found i
Bacteria are a type of biological cell. They constitute a large domain of prokaryotic microorganisms. A few micrometres in length, bacteria have a number of shapes, ranging from spheres to rods and spirals. Bacteria were among the first life forms to appear on Earth, are present in most of its habitats. Bacteria inhabit soil, acidic hot springs, radioactive waste, the deep portions of Earth's crust. Bacteria live in symbiotic and parasitic relationships with plants and animals. Most bacteria have not been characterised, only about half of the bacterial phyla have species that can be grown in the laboratory; the study of bacteria is known as a branch of microbiology. There are 40 million bacterial cells in a gram of soil and a million bacterial cells in a millilitre of fresh water. There are 5×1030 bacteria on Earth, forming a biomass which exceeds that of all plants and animals. Bacteria are vital in many stages of the nutrient cycle by recycling nutrients such as the fixation of nitrogen from the atmosphere.
The nutrient cycle includes the decomposition of dead bodies. In the biological communities surrounding hydrothermal vents and cold seeps, extremophile bacteria provide the nutrients needed to sustain life by converting dissolved compounds, such as hydrogen sulphide and methane, to energy. Data reported by researchers in October 2012 and published in March 2013 suggested that bacteria thrive in the Mariana Trench, with a depth of up to 11 kilometres, is the deepest known part of the oceans. Other researchers reported related studies that microbes thrive inside rocks up to 580 metres below the sea floor under 2.6 kilometres of ocean off the coast of the northwestern United States. According to one of the researchers, "You can find microbes everywhere—they're adaptable to conditions, survive wherever they are."The famous notion that bacterial cells in the human body outnumber human cells by a factor of 10:1 has been debunked. There are 39 trillion bacterial cells in the human microbiota as personified by a "reference" 70 kg male 170 cm tall, whereas there are 30 trillion human cells in the body.
This means that although they do have the upper hand in actual numbers, it is only by 30%, not 900%. The largest number exist in the gut flora, a large number on the skin; the vast majority of the bacteria in the body are rendered harmless by the protective effects of the immune system, though many are beneficial in the gut flora. However several species of bacteria are pathogenic and cause infectious diseases, including cholera, anthrax and bubonic plague; the most common fatal bacterial diseases are respiratory infections, with tuberculosis alone killing about 2 million people per year in sub-Saharan Africa. In developed countries, antibiotics are used to treat bacterial infections and are used in farming, making antibiotic resistance a growing problem. In industry, bacteria are important in sewage treatment and the breakdown of oil spills, the production of cheese and yogurt through fermentation, the recovery of gold, palladium and other metals in the mining sector, as well as in biotechnology, the manufacture of antibiotics and other chemicals.
Once regarded as plants constituting the class Schizomycetes, bacteria are now classified as prokaryotes. Unlike cells of animals and other eukaryotes, bacterial cells do not contain a nucleus and harbour membrane-bound organelles. Although the term bacteria traditionally included all prokaryotes, the scientific classification changed after the discovery in the 1990s that prokaryotes consist of two different groups of organisms that evolved from an ancient common ancestor; these evolutionary domains are called Archaea. The word bacteria is the plural of the New Latin bacterium, the latinisation of the Greek βακτήριον, the diminutive of βακτηρία, meaning "staff, cane", because the first ones to be discovered were rod-shaped; the ancestors of modern bacteria were unicellular microorganisms that were the first forms of life to appear on Earth, about 4 billion years ago. For about 3 billion years, most organisms were microscopic, bacteria and archaea were the dominant forms of life. Although bacterial fossils exist, such as stromatolites, their lack of distinctive morphology prevents them from being used to examine the history of bacterial evolution, or to date the time of origin of a particular bacterial species.
However, gene sequences can be used to reconstruct the bacterial phylogeny, these studies indicate that bacteria diverged first from the archaeal/eukaryotic lineage. The most recent common ancestor of bacteria and archaea was a hyperthermophile that lived about 2.5 billion–3.2 billion years ago. Bacteria were involved in the second great evolutionary divergence, that of the archaea and eukaryotes. Here, eukaryotes resulted from the entering of ancient bacteria into endosymbiotic associations with the ancestors of eukaryotic cells, which were themselves related to the Archaea; this involved the engulfment by proto-eukaryotic cells of alphaproteobacterial symbionts to form either mitochondria or hydrogenosomes, which are still found in all known Eukarya. Some eukaryotes that contained mitochondria engulfed cyanobacteria-like organisms, leading to the formation of chloroplasts in algae and plants; this is known as primary endosymbiosis. Bacteria display a wide diversity of sizes, called morphologies.
Bacterial cells are about one-tenth the size of eukaryotic cells
In enzymology, a D-alanine—D-alanine ligase is an enzyme that catalyzes the chemical reaction ATP + 2 D-alanine ⇌ ADP + phosphate + D-alanyl-D-alanineThus, the two substrates of this enzyme are ATP and D-alanine, whereas its 3 products are ADP, D-alanyl-D-alanine. This enzyme belongs to the family of ligases those forming carbon-nitrogen bonds as acid-D-amino-acid ligases; the systematic name of this enzyme class is D-alanine:D-alanine ligase. Other names in common use include alanine:alanine ligase, alanylalanine synthetase; this enzyme participates in d-alanine peptidoglycan biosynthesis. Phosphinate and D-cycloserine are known to inhibit this enzyme; the N-terminal region of the D-alanine—D-alanine ligase is thought to be involved in substrate binding, while the C-terminus is thought to be a catalytic domain. As of late 2007, 8 structures have been solved for this class of enzymes, with PDB accession codes 1EHI, 1IOV, 1IOW, 2DLN, 2FB9, 2I80, 2I87, 2I8C. Ito, E. "Enzymatic synthesis of the peptide in bacterial uridine nucleotides II.
Enzymatic synthesis and addition of D-alanyl-D-alanine". J. Biol. Chem. 237: 2696–2703. Neuhaus FC. "Kinetic studies on D-Ala-D-Ala synthetase". Fed. Proc. 21: 229. Van Heijenoort J. "Recent advances in the formation of the bacterial peptidoglycan monomer unit". Nat. Prod. Rep. 18: 503–19. Doi:10.1039/a804532a. PMID 11699883
A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough and sometimes rigid, it provides the cell with both structural support and protection, acts as a filtering mechanism. Cell walls are present in most prokaryotes, in algae and fungi but in other eukaryotes including animals. A major function is to act as pressure vessels, preventing over-expansion of the cell when water enters; the composition of cell walls varies between species and may depend on cell type and developmental stage. The primary cell wall of land plants is composed of the polysaccharides cellulose and pectin. Other polymers such as lignin, suberin or cutin are anchored to or embedded in plant cell walls. Algae possess cell walls made of glycoproteins and polysaccharides such as carrageenan and agar that are absent from land plants. In bacteria, the cell wall is composed of peptidoglycan; the cell walls of archaea have various compositions, may be formed of glycoprotein S-layers, pseudopeptidoglycan, or polysaccharides.
Fungi possess cell walls made of the N-acetylglucosamine polymer chitin. Unusually, diatoms have a cell wall composed of biogenic silica. A plant cell wall was first observed and named by Robert Hooke in 1665. However, "the dead excrusion product of the living protoplast" was forgotten, for three centuries, being the subject of scientific interest as a resource for industrial processing or in relation to animal or human health. In 1804, Karl Rudolphi and J. H. F. Link proved. Before, it had been thought that fluid passed between them this way; the mode of formation of the cell wall was controversial in the 19th century. Hugo von Mohl advocated the idea. Carl Nägeli believed that the growth of the wall in thickness and in area was due to a process termed intussusception; each theory was improved in the following decades: the apposition theory by Eduard Strasburger, the intussusception theory by Julius Wiesner. In 1930, Ernst Münch coined the term apoplast in order to separate the "living" symplast from the "dead" plant region, the latter of which included the cell wall.
By the 1980s, some authors suggested replacing the term "cell wall" as it was used for plants, with the more precise term "extracellular matrix", as used for animal cells, but others preferred the older term. Cell walls serve similar purposes in those organisms, they may give cells offering protection against mechanical stress. In multicellular organisms, they permit the organism to hold a definite shape. Cell walls limit the entry of large molecules that may be toxic to the cell, they further permit the creation of stable osmotic environments by preventing osmotic lysis and helping to retain water. Their composition and form may change during the cell cycle and depend on growth conditions. In most cells, the cell wall is flexible, meaning that it will bend rather than holding a fixed shape, but has considerable tensile strength; the apparent rigidity of primary plant tissues is enabled by cell walls, but is not due to the walls' stiffness. Hydraulic turgor pressure creates this rigidity, along with the wall structure.
The flexibility of the cell walls is seen when plants wilt, so that the stems and leaves begin to droop, or in seaweeds that bend in water currents. As John Howland explains Think of the cell wall as a wicker basket in which a balloon has been inflated so that it exerts pressure from the inside; such a basket is rigid and resistant to mechanical damage. Thus does the prokaryote cell gain strength from a flexible plasma membrane pressing against a rigid cell wall; the apparent rigidity of the cell wall thus results from inflation of the cell contained within. This inflation is a result of the passive uptake of water. In plants, a secondary cell wall is a thicker additional layer of cellulose which increases wall rigidity. Additional layers may be formed by suberin in cork cell walls; these compounds are rigid and waterproof. Both wood and bark cells of trees have secondary walls. Other parts of plants such as the leaf stalk may acquire similar reinforcement to resist the strain of physical forces.
The primary cell wall of most plant cells is permeable to small molecules including small proteins, with size exclusion estimated to be 30-60 kDa. The pH is an important factor governing the transport of molecules through cell walls. Cell walls evolved independently including within the photosynthetic eukaryotes. In these lineages, the cell wall is related to the evolution of multicellularity, terrestrialization and vascularization; the walls of plant cells must have sufficient tensile strength to withstand internal osmotic pressures of several times atmospheric pressure that result from the difference in solute concentration between the cell interior and external solutions. Plant cell walls vary from 0.1 to several µm in thickness. Up to three strata or layers may be found in plant cell walls: The primary cell wall a thin and extensible layer formed while the cell is growing; the secondary cell wall, a thick layer formed inside the primary cell wall after the cell is grown. It is not found in all cell types.
Some cells, such as the conducting cells in xylem, possess a secondary wall containing lignin, which strengthens and waterproofs the wall. The middle lamella, a layer rich in pectins; this outermost layer
Acinetobacter is a genus of Gram-negative bacteria belonging to the wider class of Gammaproteobacteria. Acinetobacter species are oxidase-negative, exhibit twitching motility, occur in pairs under magnification, they are important soil organisms, where they contribute to the mineralization of, for example, aromatic compounds. Acinetobacter species are a key source of infection in debilitated patients in the hospital, in particular the species Acinetobacter baumannii. Species of the genus Acinetobacter are aerobic, Gram-negative bacilli, they show a coccobacillary morphology on nonselective agar. Rods predominate in fluid media during early growth; the morphology of Acinetobacter species can be quite variable in Gram-stained human clinical specimens, cannot be used to differentiate Acinetobacter from other common causes of infection. Most strains of Acinetobacter, except some of the A. lwoffii strain, grow well on MacConkey agar. Although classified as not lactose-fermenting, they are partially lactose-fermenting when grown on MacConkey agar.
They are oxidase-negative, catalase-positive, indole-negative and nitrate-negative. Bacteria of the genus Acinetobacter are known to form intracellular inclusions of polyhydroxyalkanoates under certain environmental conditions. Acinetobacter is a compound word from scientific Greek; the first element acineto- appears as a somewhat baroque rendering of the Greek morpheme ακίνητο- transliterated in English is akineto-, but stems from the French cinetique and was adopted directly into English. The genus Acinetobacter comprises 38 validly named species. Identification of Acinetobacter species is complicated by lack of standard identification techniques. Identification was based on phenotypic characteristics such as growth temperature, colony morphology, growth medium, carbon sources, gelatin hydrolysis, glucose fermentation, among others; this method allowed identification of A. calcoaceticus–A. Baumannii complex by the formation of smooth, mucoid colonies at 37 °C. Related species could not be differentiated and individual species such as A. baumannii and Acinetobacter genomic species 3 could not be positively identified phenotypically.
Because routine identification in the clinical microbiology laboratory is not yet possible, Acinetobacter isolates are divided and grouped into three main complexes: Acinetobacter calcoaceticus-baumanii complex: glucose-oxidising nonhemolytic, Acinetobacter lwoffii: glucose-negative nonhemolytic Acinetobacter haemolyticus: hemolyticDifferent species of bacteria in this genus can be identified using fluorescence-lactose-denitrification to find the amount of acid produced by metabolism of glucose. The other reliable identification test at genus level is chromosomal DNA transformation assay. In this assay, a competent tryptophan auxotrophic mutant of Acinetobacter baylyi is transformed with the total DNA of a putative Acinetobacter isolate and the transformation mixture is plated on a brain heart infusion agar; the growth is harvested after incubation for 24 h at 30 °C, plating on an Acinetobacter minimal agar, incubating at 30 °C for 108 h. Growth on the AMA indicates a positive transformation assay and confirms the isolate as a member of the genus Acinetobacter.
E. coli HB101 and A. calcoaceticus MTCC1921T can be used as the negative and positive controls, respectively. Some of the molecular methods used in species identification are repetitive extragenic palindromic sequence-based PCR, pulsed field gel electrophoresis, random amplified polymorphic DNA, amplified fragment length polymorphism and sequence analysis of tRNA and 16S-23S rRNA gene spacers and amplified 16S ribosomal DNA restriction analysis. PFGE, AFLP, ARDRA are validated common methods in use today because of their discriminative ability. However, most recent methods include multilocus sequence typing and multilocus PCR and electrospray ionization mass spectrometry, which are based on amplification of conserved housekeeping genes and can be used to study the genetic relatedness between different isolates. Acinetobacter species are distributed in nature, occur in soil and water, their ability to survive on moist and dry surfaces, as well as to survive exposure to various common disinfectants, allows some Acinetobacter species to survive in a hospital environment.
Furthermore, Acinetobacter species can grow at a broad range of temperatures, allowing them to survive in a broad array of environments. Acinetobacter is isolated in nosocomial infections, is prevalent in intensive care units, where both sporadic cases and epidemic and endemic occurrences are common. A. baumannii is a frequent cause of hospital-acquired pneumonia of late-onset, ventilator-associated pneumonia. It can cause various other infections, including skin and wound infections and meningitis, but A. lwoffi is responsible for the latter. Of the Acinetobacter, A. baumannii is the greatest cause of human disease, having been implicated in a number of hospital-acquired infections such as bacteremia, urinary tract infections, secondary meningitis, infective endocarditis, wound and burn infections. In particular, A. baumannii is isolated as the cause of hospital-acquired pneumonia among patients admitted to the intensive care unit. Risk factors include tracheal or lung aspiration. In most cases of ventilator-associated pn
Serratia is a genus of Gram-negative, facultatively anaerobic, rod-shaped bacteria of the family Enterobacteriaceae. They are 1–5 μm in length and do not produce spores; the most common and pathogenic of the species in the genus, S. marcescens, is the only pathogen and causes nosocomial infections. However, rare strains of S. plymuthica, S. liquefaciens, S. rubidaea, S. odoriferae have caused diseases through infection. S. marcescens is found in showers, toilet bowls, around wetted tiles. Some members of this genus produce characteristic red pigment and can be distinguished from other members of the family Enterobacteriaceae by their unique production of three enzymes: DNase and gelatinase; the bacterium is an opportunistic human pathogen, capitalizing on its ability to form tight-knit surface communities called biofilms wherever it can. S. marcescens is thought to be transmitted through hand-to-hand transmission by hospital personnel. In the hospital, Serratia species tend to colonize the respiratory and urinary tracts, rather than the gastrointestinal tract, in adults.
Serratia infection is responsible for about 2% of nosocomial infections of the bloodstream, lower respiratory tract, urinary tract, surgical wounds, skin and soft tissues in adult patients. Outbreaks of S. marcescens meningitis, wound infections, arthritis have occurred in pediatric wards. Cases of Serratia arthritis have been reported in outpatients receiving intra-articular injections. Chronic Granulomatous Disease Human Immunodeficiency Virus Idiopathic CD4+-lymphopenia Species of Serratia have been isolated in a variety of environments, including soil, plants and air. Several methods can be used to study the epidemiology of S. marcescens. Usual enrichment strategies involve the use of media containing antibiotic and antifungal substances. A caprylate-thallous media seems to be preferred for the selective growth of genus Serratia, as it can use caprylic acid as a carbon source. Serological typing and different types of polymerase chain reaction can be used to identify the bacteria. Biotyping, bacteriocin typing, phage typing, plasmid analysis, ribotyping can be usedS.
Marcescens appears red on trypticase soy agar slants when grown at around 25 °C. S. marcescens and S. liquefaciens can be confused in the lab when using the analytical profile index system. They can both oxidise arabinose. S. marcescens was first documented as a red-coloured putrefaction of polenta by Bartolomeo Bizio in Padua. The bacterium was named in honour of Italian physicist Serafino Serrati and marcescens because of the pigment's rapid discolouration and decay