Phenol-soluble Modulin
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Phenol-soluble Modulin
Phenol-soluble modulins (PSMs) are a family of small proteins, that carry out a variety of functions, including acting as toxins, assisting in biofilm formation, and colony spreading. PSMs are produced by ''Staphylococcus'' bacteria including Methicillin-resistant ''Staphylococcus aureus'' (MRSA)'','' and ''Staphylococcus epidermidis.'' Many PSMs are encoded within the core genome and can play an important virulence factor. PSMs were first discovered in ''S. epidermidis'' by Seymour Klebanoff and via hot-phenol extraction and were described as a pro-inflammatory complex of three peptides.1. Cheung GYC, Joo HS, Chatterjee SS, Otto M. Phenol-soluble modulins - critical determinants of staphylococcal virulence. FEMS Microbiology Reviews. Blackwell Publishing Ltd; 2014. pp. 698–719. doi:10.1111/1574-6976.12057 Since their initial discovery, numerous roles of PSMs have been identified. However, due in part to the small size of many PSMs, they have largely gone unnoticed until recent y ...
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Proteins
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residues ...
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Promoter (genetics)
In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of itself, such as tRNA or rRNA. Promoters are located near the transcription start sites of genes, upstream on the DNA (towards the 5' region of the sense strand). Promoters can be about 100–1000 base pairs long, the sequence of which is highly dependent on the gene and product of transcription, type or class of RNA polymerase recruited to the site, and species of organism. Promoters control gene expression in bacteria and eukaryotes. RNA polymerase must attach to DNA near a gene for transcription to occur. Promoter DNA sequences provide an enzyme binding site. The -10 sequence is TATAAT. -35 sequences are conserved on average, but not in most promoters. Artificial promoters with conserved -10 and -35 elements transcribe more slowly. All D ...
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Staphylococcaceae
The Staphylococcaceae are a family of Gram-positive bacteria that includes the genus ''Staphylococcus'', noted for encompassing several medically significant pathogens. The five genera ''Jeotgalicoccus'', '' Macrococcus'', ''Nosocomiicoccus'', ''Salinicoccus'', and ''Staphylococcus'' have been shown to be monophyletic, while ''Gemella ''Gemella'' is a genus of Gram-positive bacteria that thrive best at high partial pressure of CO2. Description A Gemella species was first described as Neisseria hemolysans in 1938. It was reclassified as a new genus in 1960 when strains wer ...'' appears to be polyphyletic. The pathogen methicillin-resistant ''Staphylococcus aureus'' is a member of this family. References Bacillales Bacteria families {{Staphylococcaceae-stub ...
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Neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in different animals. They are formed from stem cells in the bone marrow and Cellular differentiation, differentiated into #Subpopulations, subpopulations of neutrophil-killers and neutrophil-cagers. They are short-lived and highly mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be subdivided into segmented neutrophils and banded neutrophils (or Band cell, bands). They form part of the polymorphonuclear cells family (PMNs) together with basophils and eosinophils. The name ''neutrophil'' derives from staining characteristics on hematoxylin and eosin (H&E stain, H&E) histology, histological or cell biology, cytological preparations. Whereas basophilic white blood cells stain dark blue and eosinoph ...
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Osteomyelitis
Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the feet, spine, and hips are most commonly involved in adults. The cause is usually a bacterial infection, but rarely can be a fungal infection. It may occur by spread from the blood or from surrounding tissue. Risks for developing osteomyelitis include diabetes, intravenous drug use, prior removal of the spleen, and trauma to the area. Diagnosis is typically suspected based on symptoms and basic laboratory tests as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).This is because plain radiographs are unremarkable in the first few days following acute infection. Diagnosis is further confirmed by blood tests, medical imaging, or bone biopsy. Treatment of bacterial osteomyelitis often involves both antimicrobials and sur ...
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Persister Cells
Persister cells are subpopulations of cells that resist treatment, and become antimicrobial tolerant by changing to a state of dormancy or quiescence. Persister cells in their dormancy do not divide. The tolerance shown in persister cells differs from antimicrobial resistance in that the tolerance is not inherited and is reversible. When treatment has stopped the state of dormancy can be reversed and the cells can reactivate and multiply. Most persister cells are bacterial, and there are also fungal persister cells, yeast persister cells, and cancer persister cells that show tolerance for cancer drugs. History Recognition of bacterial persister cells dates back to 1944 when Joseph Bigger, an Irish physician working in England, was experimenting with the recently discovered penicillin. Bigger used penicillin to lyse a suspension of bacteria and then inoculate a culture medium with the penicillin-treated liquid. Colonies of bacteria were able to grow after antibiotic exposure. The ...
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Neutrophil Extracellular Traps
Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind pathogens. Neutrophils are the immune system's first line of defense against infection and have conventionally been thought to kill invading pathogens through two strategies: engulfment of microbes and secretion of anti-microbials. In 2004, a novel third function was identified: formation of NETs. NETs allow neutrophils to kill extracellular pathogens while minimizing damage to the host cells. Upon ''in vitro'' activation with the pharmacological agent 12-O-Tetradecanoylphorbol-13-acetate, phorbol myristate acetate (PMA), Interleukin 8 (IL-8) or lipopolysaccharide (LPS), neutrophils release granule proteins and chromatin to form an extracellular fibril matrix known as NET through an active process. Structure and composition High-resolution scanning electron microscopy has shown that NETs consist of stretches of DNA and globular protein domains with ...
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Interleukin 17
Interleukin 17 family (IL17 family) is a family of pro-inflammatory cystine knot cytokines. They are produced by a group of T helper cell known as T helper 17 cell in response to their stimulation with IL-23. Originally, Th17 was identified in 1993 by Rouvier ''et al.'' who isolated IL17A transcript from a rodent T-cell hybridoma. The protein encoded by ''IL17A'' is a founding member of IL-17 family (see below). IL17A protein exhibits a high homology with a viral IL-17-like protein () encoded in the genome of T-lymphotropic rhadinovirus ''Herpesvirus saimiri''. In rodents, IL-17A is often referred to as CTLA8. The biologically active IL-17 interacts with type I cell surface receptor IL-17R. In turn, there are at least three variants of IL-17R referred to as IL17RA, IL17RB, and IL17RC. After binding to the receptor, IL-17 activates several signalling cascades that, in turn, lead to the induction of chemokines. Acting as chemoattractants, these chemokines recruit the immun ...
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Interleukin 8
Interleukin 8 (IL-8 or chemokine (C-X-C motif) ligand 8, CXCL8) is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel-Palade bodies. In humans, the interleukin-8 protein is encoded by the ''CXCL8'' gene. IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms. In culture, a 72 amino acid peptide is the major form secreted by macrophages. There are many receptors on the surface membrane capable of binding IL-8; the most frequently studied types are the G protein-coupled serpentine receptors CXCR1 and CXCR2. Expression and affinity for IL-8 differs between the two receptors (CXCR1 > CXCR2). Through a chain of biochemical reactions, IL-8 is secreted and is an important mediator of the immune reaction in the innate immune system response. Function IL-8, ...
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Cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents. Cytokines include chemokines, interferons, interleukins, lymphokines, and tumour necrosis factors, but generally not hormones or growth factors (despite some overlap in the terminology). Cytokines are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells; a given cytokine may be produced by more than one type of cell. They act through cell surface receptors and are especially important in the immune system; cytokines modulate the balance between humoral and cell-based immune responses, and they regulate the maturation, growth, and res ...
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RNAIII
RNAIII is a stable 514 nt regulatory RNA transcribed by the P3 promoter of the '' Staphylococcus aureus'' quorum-sensing '' agr'' system ). It is the major effector of the ''agr'' regulon, which controls the expression of many '' S. aureus'' genes encoding exoproteins and cell wall associated proteins plus others encoding regulatory proteins  The RNAIII transcript also encodes the 26 amino acid δ-haemolysin ( S''taphylococcus aureus'' delta toxin) peptide (Hld). RNAIII contains many stem loops, most of which match the Shine-Dalgarno sequence involved in translation initiation of the regulated genes. Some of these interactions are inhibitory, others stimulatory; among the former is the regulatory protein Rot. In vitro, RNAIII is expressed post exponentially, inhibiting translation of the surface proteins, notably protein A, while stimulating that of the exoproteins, many of which are tissue-degrading enzymes or cytolysins. Among the latter is the important virulence factor, α- ...
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Toxin
A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849–1919) and is derived from the word toxic. Toxins can be small molecules, peptides, or proteins that are capable of causing disease on contact with or absorption by body tissues interacting with biological macromolecules such as enzymes or cellular receptors. Toxins vary greatly in their toxicity, ranging from usually minor (such as a bee sting) to potentially fatal even at extremely low doses (such as botulinum toxin). Toxins are largely secondary metabolites, which are organic compounds that are not directly involved in an organism's growth, development, or reproduction, instead often aiding it in matters of defense. Terminology Toxins are often distinguished from other chemical agents strictly based on their biological origin. Le ...
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