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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), is a worldwide problem in clinical medicine. Despite much research and development, no vaccine for S. aureus has been approved.
Methicillin (USAN), also known as meticillin (INN), is a narrow-spectrum β-lactam antibiotic of the penicillin class.
Adhesins are cell-surface components or appendages of bacteria that facilitate adhesion or adherence to other cells or to surfaces, usually in the host they are infecting or living in. Adhesins are a type of virulence factor.
Staphylococcus epidermidis is a Gram-positive bacterium, and one of over 40 species belonging to the genus Staphylococcus. It is part of the normal human microbiota, typically the skin microbiota, and less commonly the mucosal microbiota and also found in marine sponges. It is a facultative anaerobic bacteria. Although S. epidermidis is not usually pathogenic, patients with compromised immune systems are at risk of developing infection. These infections are generally hospital-acquired. S. epidermidis is a particular concern for people with catheters or other surgical implants because it is known to form biofilms that grow on these devices. Being part of the normal skin microbiota, S. epidermidis is a frequent contaminant of specimens sent to the diagnostic laboratory.
MSCRAMM adhesin proteins mediate the initial attachment of bacteria to host tissue, providing a critical step to establish infection.
Hemolysins or haemolysins are lipids and proteins that cause lysis of red blood cells by disrupting the cell membrane. Although the lytic activity of some microbe-derived hemolysins on red blood cells may be of great importance for nutrient acquisition, many hemolysins produced by pathogens do not cause significant destruction of red blood cells during infection. However, hemolysins are often capable of lysing red blood cells in vitro.
Ceftobiprole (Zevtera/Mabelio) is a fifth-generation cephalosporin for the treatment of hospital-acquired pneumonia and community-acquired pneumonia. It is marketed by Basilea Pharmaceutica in the United Kingdom, Germany, Switzerland and Austria under the trade name Zevtera, in France and Italy under the trade name Mabelio. Like other cephalosporins, ceftobiprole exerts its antibacterial activity by binding to important penicillin-binding proteins and inhibiting their transpeptidase activity which is essential for the synthesis of bacterial cell walls. Ceftobiprole has high affinity for penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus strains and retains its activity against strains that express divergent mecA gene homologues. Ceftobiprole also binds to penicillin-binding protein 2b in Streptococcus pneumoniae (penicillin-intermediate), to penicillin-binding protein 2x in Streptococcus pneumoniae (penicillin-resistant), and to penicillin-binding protein 5 in Enterococcus faecalis.
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. 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 years.
mecA is a gene found in bacterial cells which allows them to be resistant to antibiotics such as methicillin, penicillin and other penicillin-like antibiotics.
'Staphylococcus aureus delta toxin is a toxin produced by Staphylococcus aureus. It has a wide spectrum of cytolytic activity.
The AB toxins are two-component protein complexes secreted by a number of pathogenic bacteria, though there is a pore-forming AB toxin found in the eggs of a snail. They can be classified as Type III toxins because they interfere with internal cell function. They are named AB toxins due to their components: the "A" component is usually the "active" portion, and the "B" component is usually the "binding" portion. The "A" subunit possesses enzyme activity, and is transferred to the host cell following a conformational change in the membrane-bound transport "B" subunit. These proteins consist of two independent polypeptides, which correspond to the A/B subunit moieties. The enzyme component (A) enters the cell through endosomes produced by the oligomeric binding/translocation protein (B), and prevents actin polymerisation through ADP-ribosylation of monomeric G-actin.
Bullous impetigo is a bacterial skin infection caused by Staphylococcus aureus that results in the formation of large blisters called bullae, usually in areas with skin folds like the armpit, groin, between the fingers or toes, beneath the breast, and between the buttocks. It accounts for 30% of cases of impetigo, the other 70% being non-bullous impetigo.
In molecular biology, the protein domain SdrG C terminal refers to the C terminus domain of an adhesin found only on the cell walls of bacteria. More specifically, SdrG is only found in gram-positive bacteria. This particular domain binds to a glycoprotein named fibrinogen. SdrG stands for serine-aspartate dipeptide repeats, which as its name suggests, contains repeats of two amino acids, serine and aspartate.
In molecular biology, YadA is a protein domain which is short for Yersinia adhesin A. These proteins have strong sequence and structural homology, particularly at their C-terminal end. The function is to promote their pathogenicity and virulence in host cells, though cell adhesion. YadA is found in three pathogenic species of Yersinia, Y. pestis,Y. pseudotuberculosis, and Y. enterocolitica. The YadA domain is encoded for by a virulence plasmid in Yersinia, which encodes a type-III secretion (T3S) system consisting of the Ysc injectisome and the Yop effectors.
Glutamyl endopeptidase is an extracellular bacterial serine protease of the glutamyl endopeptidase I family that was initially isolated from the Staphylococcus aureus strain V8. The protease is, hence, commonly referred to as "V8 protease", or alternatively SspA from its corresponding gene.
Aureolysin is an extracellular metalloprotease expressed by Staphylococcus aureus. This protease is a major contributor to the bacterium's virulence, or ability to cause disease, by cleaving host factors of the innate immune system as well as regulating S. aureus secreted toxins and cell wall proteins. To catalyze its enzymatic activities, aureolysin requires zinc and calcium which it obtains from the extracellular environment within the host.
Staphylococcus schleiferi is a Gram-positive, cocci-shaped bacterium of the family Staphylococcaceae. It is facultatively anaerobic, coagulase-variable, and can be readily cultured on blood agar where the bacterium tends to form opaque, non-pigmented colonies and beta (β) hemolysis. There exists two subspecies under the species S. schleiferi: Staphylococcus schleiferi subsp. schleiferi and Staphylococcus schleiferi subsp. coagulans.
Staphylococcus pseudintermedius is a gram positive coccus bacteria of the genus Staphylococcus found worldwide. It is primarily a pathogen for domestic animals, but has been known to affect humans as well. S. pseudintermedius is an opportunistic pathogen that secretes immune modulating virulence factors, has many adhesion factors, and the potential to create biofilms, all of which help to determine the pathogenicity of the bacterium. Diagnoses of Staphylococcus pseudintermedius have traditionally been made using cytology, plating, and biochemical tests. More recently, molecular technologies like MALDI-TOF, DNA hybridization and PCR have become preferred over biochemical tests for their more rapid and accurate identifications. This includes the identification and diagnosis of antibiotic resistant strains.
Beta-sandwich, β-sandwich domains consisting of 80 to 350 amino acids occur commonly in proteins. They are characterized by two opposing antiparallel beta sheets (β-sheets). The number of strands found in such domains may differ from one protein to another. β-sandwich domains are subdivided in a variety of different folds. The immunoglobulin-type fold found in antibodies (Ig-fold) consists of a sandwich arrangement of 7 and 9 antiparallel β-strands arranged in two β-sheets with a Greek-key topology. The Greek-key topology is also found in Human Transthyretin. The jelly-roll topology is found in carbohydrate binding proteins such as concanavalin A and various lectins, in the collagen binding domain of Staphylococcus aureus Adhesin and in modules that bind fibronectin as found in Tenascin. The L-type lectin domain is a variation of the jelly roll fold. The C2 domain in its typical version (PKC-C2) is a β-sandwich composed of 8 beta-strands (β-strands).
Although cell wall carbohydrates are ideal immunotherapeutic targets due to their abundance in bacteria and high level of conservation, their poor immunogenicity compared with protein targets complicates their use for the development of protective antibodies. A lysibody is a chimeric antibody in which the Fab region is the binding domain from a bacteriophage lysin, or the binding domain from an autolysin or bacteriocin, all of which bind to bacterial cell wall carbohydrate epitopes. This is linked to the Fc of Immunoglobulin G (IgG). The chimera forms a stable homodimer held together by hinge-region disulfide bonds. Thus, lysibodies are homodimeric hybrid immunoglobulin G molecules that can bind with high affinity and specificity to a carbohydrate substrate in the bacterial cell wall peptidoglycan. Lysibodies behave like authentic IgG by binding at high affinity to their bacterial wall receptor, fix complement and therefore promote phagocytosis by macrophages and neutrophils, protecting mice from infection in model systems. Since cell wall hydrolases, autolysins and bacteriocins are ubiquitous in nature, production of lysibodies specific for difficult to treat pathogenic bacteria is possible.
References
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- ↑ Jett BD, Gilmore MS (2002). "Internalization of Staphylococcus aureus by Human Corneal Epithelial Cells: Role of Bacterial Fibronectin-Binding Protein and Host Cell Factors". Infect. Immun. 70 (8): 4697–700. doi:10.1128/iai.70.8.4697-4700.2002. PMC 128182 . PMID 12117986.
- 1 2 Ahmed S, Meghji S, Williams RJ, Henderson B, Brock JH, Nair SP (2001). "Staphylococcus aureus Fibronectin Binding Proteins Are Essential for Internalization by Osteoblasts but Do Not Account for Differences in Intracellular Levels of Bacteria". Infect. Immun. 69 (5): 2872–7. doi:10.1128/IAI.69.5.2872-2877.2001. PMC 98237 . PMID 11292701.
- ↑ Williams RJ, Henderson B, Nair SP (2002). "Staphylococcus aureus fibronectin binding proteins A and B possess a second fibronectin binding region that may have biological relevance to bone tissues". Calcif Tissue Int. 70 (5): 416–21. doi:10.1007/s00223-001-2073-z. PMID 12055657.
- ↑ Huveneers S, Truong H, Fässler R, Sonnenberg A, Danen EH (2008). "Binding of soluble fibronectin to integrin alpha5 beta1 - link to focal adhesion redistribution and contractile shape". J Cell Sci. 121 (Pt 15): 2452–62. doi: 10.1242/jcs.033001 . hdl: 1887/68178 . PMID 18611961.
- ↑ Menzies BE. (2003). "The role of fibronectin binding proteins in the pathogenesis of Staphylococcus aureus infections". Current Opinion in Infectious Diseases. 16 (3): 225–9. doi:10.1097/00001432-200306000-00007. PMID 12821812.
- ↑ McCourt, Jennifer; O'Halloran, Dara P.; McCarthy, Hannah; O'Gara, James P.; Geoghegan, Joan A. (April 2014). "Fibronectin-binding proteins are required for biofilm formation by community-associated methicillin-resistant Staphylococcus aureus strain LAC". FEMS Microbiology Letters. 353 (2): 157–64. doi: 10.1111/1574-6968.12424 . hdl: 10379/12737 . PMID 24628034.
