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Anthracimycin
Anthracimycin is a polyketide antibiotic discovered in 2013. Anthracimycin is derived from marine actinobacteria. In preliminary laboratory research, it has shown activity against '' Bacillus anthracis'', the bacteria that causes anthrax, and against methicillin-resistant ''Staphylococcus aureus'' (MRSA). Discovery of anthracimycin Anthracimycin was first isolated from a species of marine '' Streptomyces'' (strain CNH365) which was collected off the shore of Santa Barbara, CA. Another strain of '' Streptomyces'' (strain T676) isolated off the coast of St. John's Island, Singapore, was found to also produce anthracimycin. This strain was found to contain the biosynthetic gene cluster for anthracimycin production. Biosynthesis Anthracimycin is the product of a type I polyketide synthase (PKS). This modular synthetic pathway uses a ''trans''- acyltransferase (AT) domain to load successive units of malonyl-CoA (MCoA) and methylmalonyl-CoA (MMCoA) to build the macrolide backb ...
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Anthracimycin Biosynthesis
Anthracimycin is a polyketide antibiotic discovered in 2013. Anthracimycin is derived from marine actinobacteria. In preliminary laboratory research, it has shown activity against ''Bacillus anthracis'', the bacteria that causes anthrax, and against methicillin-resistant ''Staphylococcus aureus'' (MRSA). Discovery of anthracimycin Anthracimycin was first isolated from a species of marine ''Streptomyces'' (strain CNH365) which was collected off the shore of Santa Barbara, CA. Another strain of ''Streptomyces'' (strain T676) isolated off the coast of St. John's Island, Singapore, was found to also produce anthracimycin. This strain was found to contain the biosynthetic gene cluster for anthracimycin production. Biosynthesis Anthracimycin is the product of a type I polyketide synthase (PKS). This modular synthetic pathway uses a ''trans''-acyltransferase (AT) domain to load successive units of malonyl-CoA (MCoA) and methylmalonyl-CoA (MMCoA) to build the macrolide backbone. Th ...
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Polyketide
Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynthesis, and application of polyketides has evolved. It is a large and diverse group of secondary metabolites caused by its complex biosynthesis which resembles that of fatty acid synthesis. Because of this diversity, polyketides can have various medicinal, agricultural, and industrial applications. Many polyketides are medicinal or exhibit acute toxicity. Biotechnology has enabled discovery of more naturally-occurring polyketides and evolution of new polyketides with novel or improved bioactivity. History Naturally produced polyketides by various plants and organisms have been used by humans since before studies on them began in the 19th and 20th century. In 1893, J. Norman Collie synthesized detectable amounts of orcinol by heating dehy ...
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Polyketide Synthase
Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynthesis, and application of polyketides has evolved. It is a large and diverse group of secondary metabolites caused by its complex biosynthesis which resembles that of fatty acid synthesis. Because of this diversity, polyketides can have various medicinal, agricultural, and industrial applications. Many polyketides are medicinal or exhibit acute toxicity. Biotechnology has enabled discovery of more naturally-occurring polyketides and evolution of new polyketides with novel or improved bioactivity. History Naturally produced polyketides by various plants and organisms have been used by humans since before studies on them began in the 19th and 20th century. In 1893, J. Norman Collie synthesized detectable amounts of orcinol by heating dehy ...
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Thioesterase
Thioesterases are enzymes which belong to the esterase family. Esterases, in turn, are one type of the several hydrolases known. Thioesterases exhibit esterase activity (splitting of an ester into acid and Alcohol (chemistry), alcohol, in the presence of water) specifically at a thiol group. Thioesterases or thiolester hydrolases are identified as members of EC 3.1.2. Family The thioesterase activity is performed by members of the acyl-CoA thioesterase (ACOT) family. The regulatory role of ACOT in fatty acid metabolism depends on their substrate (biology), substrate specificity, tissue expression and subcellular localization. For example, deactivation of fatty acids at the ER may traffic fatty acids away from pathways associated with the ER membrane, such as glycerolipid biosynthesis. Two structurally different ACOT types lead to a similar enzymatic activity in vitro, dividing the family into type I and type II ACOTs. Type I ACOTs (ACOT1–6) contain the α/β-hydrolase domain, w ...
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Post Antibiotic Effect
Antimicrobial pharmacodynamics is the relationship between the concentration of an antibiotic and its ability to inhibit vital processes of endo- or ectoparasites and microbial organisms.C.H. Nightingale, T. Murakawa, P.G. Ambrose (2002) Antimicrobial Pharmacodynamics in Theory and Clinical Practice Informa Health Care This branch of pharmacodynamics relates the concentration of an anti-infective agent to its effect, specifically to its antimicrobial effect. Concentration-dependent effects The minimum inhibitory concentration (MIC) and minimum bactericidal concentration are used to measure ''in vitro'' activity of antimicrobial agents. They are good indicators of antimicrobial potency, but don't give any information relating to time-dependent antimicrobial killing (the so-called post antibiotic effect). Post-antibiotic effect The post-antibiotic effect (PAE) is defined as persistent suppression of bacterial growth after a brief exposure (1 or 2 hours) of bacteria to an antibiotic ...
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Vancomycin-resistant Staphylococcus Aureus
Vancomycin-resistant ''Staphylococcus aureus'' (VRSA) are strains of ''Staphylococcus aureus'' that have become resistant to the glycopeptide antibiotic vancomycin. Mechanism of acquired resistance Strains of hVISA and vancomycin-intermediate ''Staphylococcus aureus'' (VISA) do not have resistant genes found in ''Enterococcus'' and the proposed mechanisms of resistance include the sequential mutations resulting in a thicker cell wall and the synthesis of excess amounts of D-ala-D-ala residues. VRSA strain acquired the vancomycin resistance gene cluster ''vanA'' from VRE. Diagnosis The diagnosis of vancomycin-resistant Staphylococcus aureus can be done with disk diffusion(and VA screen plate) Treatment of infection For isolates with a vancomycin minimum inhibitory concentration (MIC) , an alternative to vancomycin should be used. The approach is to treat with at least one agent to which VISA/VRSA is known to be susceptible by ''in vitro'' testing. The agents that are used i ...
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Staphylococcus Aureus
''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive for catalase and nitrate reduction and is a facultative anaerobe that can grow without the need for oxygen. Although ''S. aureus'' usually acts as a commensal of the human microbiota, it can also become an opportunistic pathogen, being a common cause of skin infections including abscesses, respiratory infections such as sinusitis, and food poisoning. Pathogenic strains often promote infections by producing virulence factors such as potent protein toxins, and the expression of a cell-surface protein that binds and inactivates antibodies. ''S. aureus'' is one of the leading pathogens for deaths associated with antimicrobial resistance and the emergence of antibiotic-resistant strains, such as methicillin-resistant ''S. aureus'' (MRSA ...
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Gram-negative Bacteria
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall sandwiched between an inner cytoplasmic cell membrane and a bacterial outer membrane. Gram-negative bacteria are found in virtually all environments on Earth that support life. The gram-negative bacteria include the model organism ''Escherichia coli'', as well as many pathogenic bacteria, such as ''Pseudomonas aeruginosa'', '' Chlamydia trachomatis'', and ''Yersinia pestis''. They are a significant medical challenge as their outer membrane protects them from many antibiotics (including penicillin), detergents that would normally damage the inner cell membrane, and lysozyme, an antimicrobial enzyme produced by animals that forms part of the innate immune system. Additionally, the outer leaflet of this membrane comprises a complex lipopol ...
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Gram-positive Bacteria
In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bacteria take up the crystal violet stain used in the test, and then appear to be purple-coloured when seen through an optical microscope. This is because the thick peptidoglycan layer in the bacterial cell wall retains the stain after it is washed away from the rest of the sample, in the decolorization stage of the test. Conversely, gram-negative bacteria cannot retain the violet stain after the decolorization step; alcohol used in this stage degrades the outer membrane of gram-negative cells, making the cell wall more porous and incapable of retaining the crystal violet stain. Their peptidoglycan layer is much thinner and sandwiched between an inner cell membrane and a bacterial outer membrane, causing them to take up the counterstain (sa ...
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Minimum Inhibitory Concentration
In microbiology, the minimum inhibitory concentration (MIC) is the lowest concentration of a chemical, usually a drug, which prevents visible growth of a bacterium or bacteria. MIC depends on the microorganism, the affected human being (in vivo only), and the antibiotic itself. It is often expressed in micrograms per milliliter (μg/mL) or milligrams per liter (mg/L). The MIC is determined by preparing solutions of the chemical in vitro at increasing concentrations, incubating the solutions with separate batches of cultured bacteria, and measuring the results using agar dilution or broth microdilution. Results have been graded into susceptible (often called sensitive), increased exposure, or resistant to a particular antimicrobial by using a breakpoint. Breakpoints are agreed upon values, published in guidelines of a reference body, such as the U.S. Clinical and Laboratory Standards Institute (CLSI), the British Society for Antimicrobial Chemotherapy (BSAC) or the European Committee ...
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Decalin Formation
Decalin (decahydronaphthalene, also known as bicyclo .4.0ecane and sometimes decaline), a bicyclic organic compound, is an industrial solvent. A colorless liquid with an aromatic odor, it is used as a solvent for many resins or fuel additives. Isomers Decalin occurs in ''cis'' and ''trans'' forms. The ''trans'' form is energetically more stable because of fewer steric interactions. ''cis''-Decalin is a chiral molecule without a chiral center; it has a two-fold rotational symmetry axis, but no reflective symmetry. However, the chirality is canceled through a chair-flipping process that turns the molecule into its mirror image. Image:Cis-trans isomerism of decahydronaphthalene.svg, Image:cis-decalin double chair.png, 2: Image:trans-decalin double chair.png, 3: File:Cisdecalin conformations.png, 4: ''trans''-Decalin The only possible way to join the two six-membered rings in the ''trans'' position means the second ring needs to start from two equatorial bonds (blue) of ...
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Macrolide
The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Macrolides belong to the polyketide class of natural products. Some macrolides have antibiotic or antifungal activity and are used as pharmaceutical drugs. Rapamycin is also a macrolide and was originally developed as an antifungal, but is now used as an immunosuppressant drug and is being investigated as a potential longevity therapeutic. Macrolides are bacteriostatic in that they suppress or inhibit bacterial growth rather than killing bacteria completely. Definition In general, any macrocyclic lactone having greater than 8-membered rings are candidates for this class. The macrocycle may contain amino nitrogen, amide nitrogen (but should be differentiated from cyclopeptides), an oxazole ring, or a thiazole ring. Benzene rings are exclude ...
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