Stafylokocker aureus hur tas odlingen

Staphylococcus aureus

Species of gram-positive bacterium

Medical condition

Staphylococcus aureus
Other names	Staph aureus, S. aureus
Specialty	Infectious disease
Types	Methicillin-susceptible Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus
Causes	Staphylococcus aureus bacteria
Differential diagnosis	other bacterial, viral and fungal infections,
Prevention	hand tvätt, cleaning surfaces
Medication	Antibiotics
Frequency	20% to 30% of the human population often without symptoms

Staphylococcus aureus fryst vatten a gram-positivespherically shapedbacterium, a member of the Bacillota, and fryst vatten a usual member of the microbiota of the body, frequently funnen in the upper respiratory tract and on the skin.

It fryst vatten often positiv for catalase and nitrate reduction and fryst vatten a facultative anaerobe, meaning that it can grow without oxygen.^[1] 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 bygd producing virulence factors such as potent proteintoxins, and the expression of a cell-surface protein that binds and inactivates antibodies. S. aureus fryst vatten 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). The bacterium fryst vatten a worldwide bekymmer in clinical medicin. Despite much research and development, no vaccine for S. aureus has been approved.

An estimated 21% to 30% of the human population are long-term carriers of S. aureus,^[2]^[3] which can be funnen as part of the normal skin microbiota, in the nostrils,^[2]^[4] and as a normal inhabitant of the lower fortplantnings- tract of females.^[5]^[6]S.

aureus can cause a range of illnesses, from minor skin infections, such as pimples,^[7]impetigo, boils, cellulitis, folliculitis, carbuncles, scalded skin syndrome, and abscesses, to life-threatening diseases such as pneumonia, meningitis, osteomyelitis, endocarditis, toxic chock syndrome, bacteremia, and sepsis. It fryst vatten still one of the fem most common causes of hospital-acquired infections and fryst vatten often the cause of wound infections following surgery.

Each year, around 500,000 hospital patients in the United States contract a staphylococcal infection, chiefly bygd S. aureus.^[8] Up to 50,000 deaths each year in the U.S. are linked to staphylococcal infection.^[9]

History

[edit]

Discovery

[edit]

In 1880, Alexander Ogston, a Scottish surgeon, discovered that Staphylococcus can cause wound infections after noticing groups of bacteria in pus from a surgical varböld during a procedure he was performing.

He named it Staphylococcus after its clustered appearance evident beneath a microscope. Then, in 1884, German forskare Friedrich Julius Rosenbach identified Staphylococcus aureus, discriminating and separating it from Staphylococcus albus, a related bacterium. In the early 1930s, doctors began to use a more streamlined test to detect the presence of an S.

aureus infection bygd the means of coagulase testing, which enables detection of an enzyme produced bygd the bacterium. Prior to the 1940s, S. aureus infections were fatal in the majority of patients. However, doctors discovered that the use of penicillin could cure S. aureus infections. Unfortunately, bygd the end of the 1940s, penicillin resistance became widespread amongst this bacterium population and outbreaks of the resistant strain began to occur.^[10]

Evolution

[edit]

Staphylococcus aureus can be sorted into ten dominant human lineages.^[11] There are numerous minor lineages as well, but these are not seen in the population as often.

Genomes of bacteria within the same lineage are mostly conserved, with the undantag of mobile genetic elements. Mobile genetic elements that are common in S. aureus include bacteriophages, pathogenicity islands, plasmids, transposons, and staphylococcal cassette chromosomes. These elements have enabled S. aureus to continually evolve and gain new traits. There fryst vatten a great deal of genetic variation within the S.

aureus species. A study bygd Fitzgerald et al. (2001) revealed that approximately 22% of the S. aureus genome fryst vatten non-coding and thus can differ from bacterium to bacterium. An example of this difference fryst vatten seen in the species' virulence. Only a few strains of S. aureus are associated with infections in humans.

This demonstrates that there fryst vatten a large range of infectious ability within the species.^[12]

It has been proposed that one possible reason for the great deal of heterogeneity within the species could be due to its reliance on heterogeneous infections. This occurs when multiple different types of S.

aureus cause an infection within a host. The different strains can secrete different enzymes or bring different antibiotic resistances to the group, increasing its pathogenic ability.^[13] Thus, there fryst vatten a need for a large number of mutations and acquisitions of mobile genetic elements.^{[citation needed]}

Another notable evolutionary process within the S.

aureus species fryst vatten its co-evolution with its human hosts. Over time, this parasitic relationship has led to the bacterium's ability to be carried in the nasopharynx of humans without causing symptoms or infection. This allows it to be passed throughout the human population, increasing its fitness as a species.^[14] However, only approximately 50% of the human population are carriers of S.

aureus, with 20% as continuous carriers and 30% as intermittent. This leads scientists to believe that there are many factors that determine whether S. aureus fryst vatten carried asymptomatically in humans, including factors that are specific to an individual individ. According to a 1995 study bygd Hofman et al., these factors may include age, sex, diabetes, and smoking.

They also determined some genetic variations in humans that lead to an increased ability for S. aureus to colonize, notably a polymorphism in the glucocorticoid receptor gene that results in larger corticosteroid production. In conclusion, there fryst vatten bevis that any strain of this bacterium can become invasive, as this fryst vatten highly dependent upon human factors.^[15]

Though S.

aureus has quick fortplantnings- and micro-evolutionary rates, there are multiple barriers that prevent evolution with the species. One such barrier fryst vatten AGR, which fryst vatten a global accessory gene regulator within the bacteria. This such regulator has been linked to the virulence level of the bacteria. Loss of function mutations within this gene have been funnen to increase the fitness of the bacterium containing it.

Thus, S. aureus must man a trade-off to increase their success as a species, exchanging reduced virulence for increased drug resistance. Another barrier to evolution fryst vatten the Sau1 Type inom restriction modification (RM) struktur. This struktur exists to skydda the bacterium from utländsk DNA bygd digesting it. Exchange of DNA between the same lineage fryst vatten not blocked, since they have the same enzymes and the RM struktur does not recognize the new DNA as utländsk, but transfer between different lineages fryst vatten blocked.^[13]

Microbiology

[edit]

Staphylococcus aureus (,^[16]^[17]Greek σταφυλόκοκκος, "grape-cluster berry", Latinaureus, "golden") fryst vatten a facultative anaerobic, gram-positive coccal (round) bacterium also known as "golden staph" and "oro staphira".

S. aureus fryst vatten nonmotile and does not struktur spores.^[18] In medical literature, the bacterium fryst vatten often referred to as S. aureus, Staph aureus or Staph a..^[19]S. aureus appears as bakterier (grape-like clusters) when viewed through a microscope, and has large, round, golden-yellow colonies, often with hemolysis, when grown on blood agar plates.^[20]S.

aureusreproduces asexually bygd binary fission. Complete separation of the daughter cells fryst vatten mediated bygd S. aureusautolysin, and in its absence or targeted inhibition, the daughter cells remain attached to one another and appear as clusters.^[21]

Staphylococcus aureus fryst vatten catalase-positive (meaning it can tillverka the enzyme catalase).

Catalase converts hydrogen peroxide (H
₂O
₂) to vatten and oxygen. Catalase-activity tests are sometimes used to distinguish bakterier from enterococci and streptococci. Previously, S. aureus was differentiated from other bakterier bygd the coagulase test.

Bakterierna kan växa och bilda ett gift om maten sedan inte förvaras i rätt temperatur

However, not all S. aureus strains are coagulase-positive^[20]^[22] and incorrect species identification can impact effective treatment and control measures.^[23]

Natural genetic transformation fryst vatten a fortplantnings- process involving DNA transfer from one bacterium to another through the intervening medium, and the integration of the donor sequence into the recipient genome bygd homologous recombination.

S. aureus was funnen to be capable of natural genetic transformation, but only at low frequency beneath the experimental conditions employed.^[24] Further studies suggested that the development of competence for natural genetic transformation may be substantially higher beneath appropriate conditions, yet to be discovered.^[25]

Role in health

[edit]

In humans, S.

aureus can be present in the upper respiratory tract, gut mucosa, and skin as a member of the normal microbiota.^[26]^[27]^[28] However, because S. aureus can cause disease beneath certain host and environmental conditions, it fryst vatten characterized as a "pathobiont".^[26]

Role in disease

[edit]

Further information: Coagulase-positive staphylococcal infection

While S.

aureus usually acts as a commensal bacterium, asymptomaticallycolonizing about 30% of the human population, it can sometimes cause disease.^[3] In particular, S. aureus fryst vatten one of the most common causes of bacteremia and infective endocarditis. Additionally, it can cause various skin and soft-tissue infections,^[3] particularly when skin or mucosal barriers have been breached.

Staphylococcus aureus infections can spread through contact with pus from an infected wound, skin-to-skin contact with an infected individ, and contact with objects used bygd an infected individ such as towels, sheets, clothing, or athletic utrustning. Joint replacements put a individ at particular fara of septic arthritis, staphylococcal endocarditis (infection of the heart valves), and pneumonia.^[29]

Staphylococcus aureus fryst vatten a significant cause of chronic biofilm infections on medical implants, and the repressor of toxins fryst vatten part of the infection pathway.^[30]

Staphylococcus aureus can lie dormant in the body for years undetected.

Once symptoms begin to show, the host fryst vatten contagious for another two weeks, and the overall illness lasts a few weeks. If untreated, though, the disease can be deadly.^[31] Deeply penetrating S. aureus infections can be severe.^{[citation needed]}

Skin infections

[edit]

Skin infections are the most common form eller gestalt of S.

aureus infection. This can manifest in various ways, including small benign boils, folliculitis, impetigo, cellulitis, and more severe, invasive soft-tissue infections.^[7]^[3]

Staphylococcus aureus fryst vatten extremely prevalent in persons with atopic dermatitis (AD), more commonly known as eczema.^[32] It fryst vatten mostly funnen in fertile, active places, including the armpits, hair, and scalp.

Large pimples that appear in those areas may exacerbate the infection if söndersliten. Colonization of S. aureus drives inflammation of AD.^[33]^[32]S. aureus fryst vatten believed to exploit defects in the skin barrier of persons with atopic dermatitis, triggering cytokine expression and therefore exacerbating symptoms.^[34] This can lead to staphylococcal scalded skin syndrome, a severe struktur of which can be seen in newborns.^[35]

Antibiotics are commonly used to mål overgrowth of S.

[1]

aureus but their benefit fryst vatten limited and they increase the fara of antimicrobial resistance. For these reasons, they are only recommended for people who not only present symptoms on the skin but feel systematically unwell.^[36]^[37]^[38]

Food poisoning

[edit]

Staphylococcus aureus fryst vatten also responsible for food poisoning and achieves this bygd generating toxins in the food, which fryst vatten then ingested.^[39] Its incubation period lasts 30 minutes to eight hours,^[40] with the illness itself lasting from 30 minutes to 3 days.^[41] Preventive measures one can take to help prevent the spread of the disease include tvätt hands thoroughly with soap and vatten before preparing food.

The Centers for Disease Control and Prevention recommends staying away from any food if ill, and wearing handskar if any open wounds occur on hands or wrists while preparing food. If storing food for längre than 2 hours, it fryst vatten recommended to keep the food below 4.4 or above 60 °C (below 40 or above 140 °F).^[42]

Bone and joint infections

[edit]

Staphylococcus aureus fryst vatten a common cause of major bone and joint infections, including osteomyelitis, septic arthritis, and infections following joint replacement surgeries.^[43]^[3]^[44]

Bacteremia

[edit]

Staphylococcus aureus fryst vatten a leading cause of bloodstream infections throughout much of the industrialized world.^[43] Infection fryst vatten generally associated with breaks in the skin or mucosal membranes due to surgery, injury, or use of intravascular devices such as cannulas, hemodialysis machines, or hypodermic needles.^[3]^[43] Once the bacteria have entered the bloodstream, they can infect various organs, causing infective endocarditis, septic arthritis, and osteomyelitis.^[43] This disease fryst vatten particularly prevalent and severe in the very ung and very old.^[3]

Without antibiotic treatment, S.

aureus bacteremia has a case fatality rate around 80%.^[3] With antibiotic treatment, case fatality rates range from 15% to 50% depending on the age and health of the patient, as well as the antibiotic resistance of the S. aureus strain.^[3]

Medical implant infections

[edit]

Staphylococcus aureus fryst vatten often funnen in biofilms formed on medical devices implanted in the body or on human tissue.

It fryst vatten commonly funnen with another pathogen, Candida albicans, forming multispecies biofilms. The latter fryst vatten suspected to help S. aureus penetrate human tissue.^[9] A higher mortality fryst vatten linked with multispecies biofilms.^[45]

Staphylococcus aureus biofilm fryst vatten the predominant cause of orthopedic implant-related infections, but fryst vatten also funnen on cardiac implants, vascular grafts, various catheters, and cosmetic surgical implants.^[46]^[47] After implantation, the surface of these devices becomes coated with host proteins, which provide a rik surface for bacterial attachment and biofilm formation.

Once the device becomes infected, it must be completely removed, since S. aureus biofilm cannot be destroyed bygd antibiotic treatments.^[47]

Current therapy for S. aureus biofilm-mediated infections involves surgical removal of the infected device followed bygd antibiotic treatment. Conventional antibiotic treatment alone fryst vatten not effective in eradicating such infections.^[46] An alternative to postsurgical antibiotic treatment fryst vatten using antibiotic-loaded, dissolvable calcium sulfate beads, which are implanted with the medical device.

These beads can release high doses of antibiotics at the desired site to prevent the första infection.^[47]

Novel treatments for S. aureus biofilm involving nano silver particles, bacteriophages, and plant-derived antibiotic agents are being studied. These agents have shown inhibitory effects against S. aureus embedded in biofilms.^[48] A class of enzymes have been funnen to have biofilm matrix-degrading ability, thus may be used as biofilm dispersal agents in combination with antibiotics.^[49]

Animal infections

[edit]

Staphylococcus aureus can survive on dogs,^[50] cats,^[51] and horses,^[52] and can cause bumblefoot in chickens.^[53] Some believe health-care workers' dogs should be considered a significant source of antibiotic-resistant S.

aureus, especially in times of outbreak.^[50] In a 2008 study bygd Boost, O'Donoghue, and James, it was funnen that just about 90% of S. aureus colonized within husdjur dogs presented as resistant to at least one antibiotic. The nasal område has been implicated as the most important site of transfer between dogs and humans.^[54]

Staphylococcus aureus fryst vatten one of the causal agents of mastitis in dairy cows.

Its large polysaccharide capsule protects the organism from recognition bygd the cow's immune defenses.^[55]

Virulence factors

[edit]

Main article: Virulence factor

Enzymes

[edit]

Staphylococcus aureus produces various enzymes such as coagulase (bound and free coagulases) which facilitates the konvertering of fibrinogen to fibrin to cause clots which fryst vatten important in skin infections.^[56]Hyaluronidase (also known as spreading factor) breaks down hyaluronic acid and helps in spreading it.

Deoxyribonuclease, which breaks down the DNA, protects S.

[2][3] S

aureus from neutrophil extracellular trap-mediated killing.^[57]^[58]S. aureus also produces lipase to digest lipids, staphylokinase to dissolve fibrin and aid in spread, and beta-lactamase for drug resistance.^[59]

Toxins

[edit]

Depending on the strain, S. aureus fryst vatten capable of secreting several exotoxins, which can be categorized into three groups.

Many of these toxins are associated with specific diseases.^[60]

Superantigens

Antigens known as superantigens can induce toxic chock syndrome (TSS). This group comprises 25 staphylococcal enterotoxins (SEs) which have been identified to date and named alphabetically (SEA - SEZ),^[61] including enterotoxin type B as well as the toxic chock syndrome toxin TSST-1 which causes TSS associated with tampon use.

Toxic chock syndrome fryst vatten characterized bygd fever, erythematous rash, low blood pressure, chock, multiple kroppsdel failure, and skin peeling. Lack of antibody to TSST-1 plays a part in the pathogenesis of TSS. Other strains of S. aureus can tillverka an enterotoxin that fryst vatten the causative agent of a type of gastroenteritis. This struktur of gastroenteritis fryst vatten self-limiting, characterized bygd vomiting and diarrhea 1–6 hours after ingestion of the toxin, with recovery in 8 to 24 hours.

Symptoms include nausea, vomiting, diarrhea, and major abdominal pain.^[62]^[63]

Exfoliative toxins

Type VII Secretion system

[edit]

See also: Type VII secretion struktur (T7SS)

A secretion struktur fryst vatten a highly specialised multi-protein enhet that fryst vatten embedded in the fängelse envelope with the function of translocating effector proteins from inre of the fängelse to the extracellular space or into a mål host cytosol.

The exact structure and function of T7SS fryst vatten yet to be fully elucidated. Currently, kvartet proteins are known components of S. aureus type VII secretion system; EssC fryst vatten a large integral membrane ATPase - which most likely powers the secretion systems and has been hypothesised forming part of the translocation kanal. The other proteins are EsaA, EssB, EssA, that are membrane proteins that function alongside EssC to medla protein secretion.

The exact mechanism of how substrates reach the fängelse surface fryst vatten unknown, as fryst vatten the interaction of the three membrane proteins with each other and EssC.^[66]

T7 dependent effector proteins

EsaD fryst vatten DNA endonuclease toxin secreted bygd S. aureus, has been shown to hämma growth of competitor S.

aureus strain in vitro.^[67] EsaD fryst vatten cosecreted with chaperone EsaE, which stabilises EsaD structure and brings EsaD to EssC for secretion.^[67]^[66] Strains that tillverka EsaD also co-produce EsaG, a cytoplasmic anti-toxin that protects the producer strain from EsaD's toxicity.^[67]

TspA fryst vatten another toxin that mediates intraspecies competition.

It fryst vatten a bacteriostatic toxin that has a membrane depolarising activity facilitated bygd its C-terminal domain. Tsai fryst vatten a transmembrane protein that confers immunity to the producer strain of TspA, as well as the attacked strains. There fryst vatten genetic variability of the C-terminal domain of TspA therefore, it seems like the strains may producera different TspA variants to increase competitiveness.^[68]

Toxins that play a role in intraspecies competition confers an advantage bygd promoting successful colonisation in polymicrobial communities such as the nasopharynx and lung bygd outcompeting lesser strains.^[68]

There are also T7 effector proteins that play role a in pathogenesis, for example mutational studies of S.

aureus have suggested that EsxB and EsxC contribute to persistent infection in a murine varböld model.^[69]

EsxX has been implicated in neutrophil lysis, therefore suggested as contributing to the evasion of host immune struktur. Deletion of essX in S. aureus resulted in significantly reduced resistance to neutrophils and reduced virulence in murine skin and blood infection models.^[70]

Altogether, T7SS and known secreted effector proteins are a strategy of pathogenesis bygd improving fitness against competitor S.

aureus species as well as increased virulence via evading the innate immune struktur and optimising persistent infections.^{[citation needed]}

Small RNA

[edit]

The list of small RNAs involved in the control of bacterial virulence in S. aureus fryst vatten growing. This can be facilitated bygd factors such as increased biofilm formation in the presence of increased levels of such small RNAs.^[71] For example, RNAIII,^[72]SprD,^[73] SprC,^[74]^[75]RsaE,^[76] SprA1,^[77] SSR42,^[78] ArtR,^[79]SprX, and Teg49.^[80]

DNA repair

[edit]

Host neutrophils cause DNA double-strand breaks in S.

aureus through the production of reactive oxygen species.^[81] For infection of a host to be successful, S. aureus must survive such damages caused bygd the hosts' defenses. The two protein complex RexAB encoded bygd S. aureus fryst vatten employed in the recombinational repair of DNA double-strand breaks.^[81]

Strategies for post-transcriptional regulation bygd 3'untranslated region

[edit]

Many mRNAs in S.

aureus carry three prime untranslated regions (3'UTR) längre than 100 nucleotides, which may potentially have a regulatory function.^[82]

Further investigation of icaR mRNA (mRNA coding for the repressor of the main expolysaccharidic compound of the bacteria biofilm matrix) demonstrated that the 3'UTR binding to the 5' UTR can interfere with the translation initiation complex and generate a double stranded substrate for RNase III.

The interaction fryst vatten between the UCCCCUG motif in the 3'UTR and the Shine-Dalagarno område at the 5'UTR. Deletion of the motif resulted in IcaR repressor accumulation and inhibition of biofilm development.^[82] The biofilm formation fryst vatten the main cause of Staphylococcus implant infections.^[83]

Biofilm

[edit]

Biofilms are groups of microorganisms, such as bacteria, that attach to each other and grow on wet surfaces.^[84] The S.

aureus biofilm fryst vatten embedded in a glycocalyx slime layer and can consist of teichoic acids, host proteins, extracellular DNA (eDNA) and sometimes polysaccharide intercellular antigen (PIA). S. aureus biofilms are important in disease pathogenesis, as they can contribute to antibiotic resistance and immune struktur evasion.^[47]S.

aureus biofilm has high resistance to antibiotic treatments and host immune response.^[84] One hypothesis for explaining this fryst vatten that the biofilm matrix protects the embedded cells bygd acting as a barrier to prevent antibiotic penetration. However, the biofilm matrix fryst vatten composed with many vatten channels, so this hypothesis fryst vatten becoming increasingly less likely, but a biofilm matrix possibly contains antibiotic‐degrading enzymes such as β-lactamases, which can prevent antibiotic penetration.^[85] Another hypothesis fryst vatten that the conditions in the biofilm matrix favor the formation of persister cells, which are highly antibiotic-resistant, dormant bacterial cells.^[47]S.

aureus biofilms also have high resistance to host immune response. Though the exact mechanism of resistance fryst vatten unknown, S. aureus biofilms have increased growth beneath the presence of cytokines produced bygd the host immune response.^[86] Host antibodies are less effective for S. aureus biofilm due to the heterogeneous antigen leverans, where an antigen may be present in some areas of the biofilm, but completely absent from other areas.^[47]

Studies in biofilm development have shown to be related to changes in gene expression.

There are specific genes that were funnen to be crucial in the different biofilm growth stages. Two of these genes include rocD and gudB, which koda for the enzyme's ornithine-oxo-acid transaminase and glutamate dehydrogenase, which are important for amino acid metabolism. Studies have shown biofilm development rely on amino acids glutamine and glutamate for proper metabolic functions.^[87]

Other immunoevasive strategies

[edit]

Protein A

Protein A fryst vatten anchored to staphylococcal peptidoglycan pentaglycine bridges (chains of fem glycine residues) bygd the transpeptidasesortase A.^[88] Protein A, an IgG-binding protein, binds to the Fc område of an antibody.

In fact, studies involving mutation of genes coding for protein A resulted in a lowered virulence of S. aureus as measured bygd survival in blood, which has led to speculation that protein A-contributed virulence requires binding of antibody Fc regions.^[89]

Protein A in various recombinant forms has been used for decades to bind and purify a bred range of antibodies bygd immunoaffinity chromatography.

Transpeptidases, such as the sortases responsible for anchoring factors like protein A to the staphylococcal peptidoglycan, are being studied in hopes of developing new antibiotics to mål MRSA infections.^[90]

Staphylococcal pigments

Some strains of S.

aureus are capable of producing staphyloxanthin — a golden-coloured carotenoidpigment. This pigment acts as a virulence factor, primarily bygd being a bacterial antioxidant which helps the microbe evade the reactive oxygen species which the host immune struktur uses to kill pathogens.^[91]^[92]

Mutant strains of S. aureus modified to lack staphyloxanthin are less likely to survive incubation with an oxidizing kemikalie, such as hydrogen peroxide, than pigmented strains.

Mutant colonies are quickly killed when exposed to human neutrophils, while many of the pigmented colonies survive.^[91] In mice, the pigmented strains cause lingering abscesses when inoculated into wounds, whereas wounds infected with the unpigmented strains quickly heal.^{[citation needed]}

These tests suggest the Staphylococcus strains use staphyloxanthin as a defence against the normal human immune struktur.

Drugs designed to hämma the production of staphyloxanthin may weaken the bacterium and renew its susceptibility to antibiotics.^[92] In fact, because of similarities in the pathways for biosynthesis of staphyloxanthin and human cholesterol, a drug developed in the context of cholesterol-lowering therapy was shown to block S.

aureus pigmentation and disease progression in a mouse infection model.^[93]

Classical diagnosis

[edit]

Depending upon the type of infection present, an appropriate specimen fryst vatten obtained accordingly and sent to the laboratory for definitive identification bygd using biochemical or enzyme-based tests.

A Gram stain fryst vatten first performed to guide the way, which should show typical gram-positive bacteria, cocci, in clusters. Second, the isolera fryst vatten cultured on mannitol krydda agar, which fryst vatten a selective medium with 7.5% NaCl that allows S. aureus to grow, producing yellow-colored colonies as a result of mannitol fermentation and subsequent drop in the medium's pH.^[94]^[95]

Furthermore, for differentiation on the species level, catalase (positive for all Staphylococcus species), coagulase (fibrin clot formation, positiv for S.

aureus), DNAse (zone of clearance on DNase agar), lipase (a yellow color and rancid odor smell), and phosphatase (a pink color) tests are all done. For staphylococcal food poisoning, phage typing can be performed to determine whether the bakterier recovered from the food were the source of infection.^[96]

Rapid diagnosis and typing

[edit]

Diagnostic microbiology laboratories and reference laboratories are key for identifying outbreaks and new strains of S.

aureus. Recent genetic advances have enabled reliable and rapid techniques for the identification and characterization of clinical isolates of S. aureus in real time. These tools support infection control strategies to limit bacterial spread and ensure the appropriate use of antibiotics. Quantitative PCR fryst vatten increasingly being used to identify outbreaks of infection.^[97]^[98]

When observing the evolvement of S.

Gula stafylokocker kan orsaka olika sorters hudinfektioner med utslag och bölder

aureus and its ability to adapt to each modified antibiotic, two basic methods known as "band-based" or "sequence-based" are employed.^[99] Keeping these two methods in mind, other methods such as multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), bacteriophage typing, kurort locus typing, and SCCmec typing are often conducted more than others.^[100] With these methods, it can be determined where strains of MRSA originated and also where they are currently.^[101]

With MLST, this technique of typing uses fragments of several housekeeping genes known as aroE, glpF, gmk, pta, tip, and yqiL.

These sequences are then assigned a number which give to a string of several numbers that serve as the allelic beskrivning. Although this fryst vatten a common method, a limitation about this method fryst vatten the maintenance of the microarray which detects newly allelic profiles, making it a costly and time-consuming experiment.^[99]

With PFGE, a method which fryst vatten still very much used dating back to its first success in 1980s, remains capable of helping differentiate MRSA isolates.^[101] To accomplish this, the technique uses multiple gel electrophoresis, along with a voltage gradient to display klar resolutions of molecules.

The S. aureus fragments then transition down the gel, producing specific grupp patterns that are later compared with other isolates in hopes of identifying related strains. Limitations of the method include practical difficulties with uniform grupp patterns and PFGE sensitivity as a whole.^{[citation needed]}

Spa locus typing fryst vatten also considered a popular technique that uses a single locus zone in a polymorphic område of S.

aureus to distinguish any form eller gestalt of mutations.^[101] Although this technique fryst vatten often inexpensive and less time-consuming, the chance of losing discriminatory power making it hard to differentiate between MLST clonal complexes exemplifies a crucial limitation.^{[citation needed]}

Treatment

[edit]

For susceptible strains, the treatment of choice for S.

aureus infection fryst vatten penicillin. An antibiotic derived from some Penicilliumfungal species, penicillin inhibits the formation of peptidoglycan cross-linkages that provide the rigidity and strength in a bacterial fängelse vägg. The four-membered β-lactam fingerprydnad of penicillin fryst vatten bound to enzyme DD-transpeptidase, an enzyme that when functional, cross-links chains of peptidoglycan that struktur bacterial fängelse walls.

The binding of β-lactam to DD-transpeptidase inhibits the enzyme's functionality and it can no längre catalyze the formation of the cross-links. As a result, fängelse vägg formation and degradation are imbalanced, thus resulting in fängelse death. In most countries, however, penicillin resistance fryst vatten extremely common (>90%), and first-line therapy fryst vatten most commonly a penicillinase-resistant β-lactam antibiotic (for example, oxacillin or flucloxacillin, both of which have the same mechanism of action as penicillin) or vancomycin, depending on local resistance patterns.

Combination therapy with gentamicin may be used to treat serious infections, such as endocarditis,^[102]^[103] but its use fryst vatten controversial because of the high fara of damage to the kidneys.^[104] The duration of treatment depends on the site of infection and on severity. Adjunctive rifampicin has been historically used in the management of S aureus bacteraemia, but randomised controlled rättegång bevis has shown this to be of no overall benefit over standard antibiotic therapy.^[105]

Antibiotic resistance in S.

aureus was uncommon when penicillin was first introduced in 1943. Indeed, the original Petri dish on which Alexander Fleming of Imperial College London observed the antibacterial activity of the Penicillium fungus was growing a culture of S. aureus. bygd 1950, 40% of hospital S. aureus isolates were penicillin-resistant; bygd 1960, this had risen to 80%.^[106]

Methicillin-resistant bakterie aureus (MRSA, often pronounced or ), fryst vatten one of a number of greatly feared strains of S.

aureus which have become resistant to most β-lactam antibiotics. For this reason, vancomycin, a glycopeptide antibiotic, fryst vatten commonly used to combat MRSA.

[1] Infections are common both in community-acquired as well as hospital-acquired settings and treatment remains challenging to manage due to the emergence of multi-drug resistant strains such as MRSA (Methicillin-Resistant Staphylococcus aureus)

Vancomycin inhibits the synthesis of peptidoglycan, but unlike β-lactam antibiotics, glycopeptide antibiotics mål and bind to amino acids in the fängelse vägg, preventing peptidoglycan cross-linkages from forming. MRSA strains are most often funnen associated with institutions such as hospitals, but are becoming increasingly prevalent in community-acquired infections.^{[citation needed]}

Minor skin infections can be treated with triple antibiotic ointment.^[107] One topical agent that fryst vatten prescribed fryst vatten mupirocin, a protein synthesis inhibitor that fryst vatten produced naturally bygd Pseudomonas fluorescens and has seen success for treatment of S.

aureus nasal carriage.^[47]

Antibiotic resistance

[edit]

Main article: Antimicrobial resistance

Staphylococcus aureus was funnen to be the second leading pathogen for deaths associated with antimicrobial resistance in 2019.^[108]

Staphylococcal resistance to penicillin fryst vatten mediated bygd penicillinase (a struktur of beta-lactamase) production: an enzyme that cleaves the β-lactam fingerprydnad of the penicillin molekyl, rendering the antibiotic ineffective.

Penicillinase-resistant β-lactam antibiotics, such as methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, and flucloxacillin are able to resist degradation bygd staphylococcal penicillinase.^{[citation needed]}

Resistance to methicillin fryst vatten mediated via the mecoperon, part of the staphylococcal cassette chromosome mec (SCCmec).

SCCmec fryst vatten a family of mobile genetic elements, which fryst vatten a major driving force of S. aureus evolution.^[99] Resistance fryst vatten conferred bygd the mecA gene, which codes for an altered penicillin-binding protein (PBP2a or PBP2') that has a lower affinity for binding β-lactams (penicillins, cephalosporins, and carbapenems).

This allows for resistance to all β-lactam antibiotics, and obviates their clinical use during MRSA infections. Studies have explained that this mobile genetic element has been acquired bygd different lineages in separate gene transfer events, indicating that there fryst vatten not a common ancestor of differing MRSA strains.^[109] Interestingly, one study suggests that MRSA sacrifices virulence, for example, toxin production and invasiveness, for survival and creation of biofilms^[110]

Aminoglycoside antibiotics, such as kanamycin, gentamicin, streptomycin, were once effective against staphylococcal infections until strains evolved mechanisms to hämma the aminoglycosides' action, which occurs via protonated amine and/or hydroxyl interactions with the ribosomal RNA of the bacterial 30S ribosomal subunit.^[111] Three main mechanisms of aminoglycoside resistance mechanisms are currently and widely accepted: aminoglycoside modifying enzymes, ribosomal mutations, and active efflux of the drug out of the bacteria.^{[citation needed]}

Aminoglycoside-modifying enzymes inactivate the aminoglycoside bygd covalently attaching either a phosphate, nucleotide, or kemisk grupp i organiska föreningar moiety to either the amine or the alcohol key functional group (or both groups) of the antibiotic.

This changes the charge or sterically hinders the antibiotic, decreasing its ribosomal binding affinity. In S. aureus, the best-characterized aminoglycoside-modifying enzyme fryst vatten aminoglycoside adenylyltransferase 4' IA (ANT(4')IA). This enzyme has been solved bygd X-ray crystallography.^[112] The enzyme fryst vatten able to attach an adenyl moiety to the 4' hydroxyl group of many aminoglycosides, including kanamycin and gentamicin.^{[citation needed]}

Glycopeptide resistance fryst vatten typically mediated bygd acquisition of the vanA gene, which originates from the Tn1546 transposon funnen in a plasmid in enterococci and codes for an enzyme that produces an alternative peptidoglycan to which vancomycin will not bind.^[113]

Today, S.

aureus has become resistant to many commonly used antibiotics. In the UK, only 2% of all S. aureus isolates are sensitive to penicillin, with a similar picture in the rest of the world. The β-lactamase-resistant penicillins (methicillin, oxacillin, cloxacillin, and flucloxacillin) were developed to treat penicillin-resistant S.

aureus, and are still used as first-line treatment. Methicillin was the first antibiotic in this class to be used (it was introduced in 1959), but only two years later, the first case of methicillin-resistant Staphylococcus aureus (MRSA) was reported in England.^[114]

Despite this, MRSA generally remained an uncommon finding, even in hospital settings, until the 1990s, when the MRSA prevalence in hospitals exploded, and it fryst vatten now endemic.^[115] Now, methicillin-resistant Staphylococcus aureus (MRSA) fryst vatten not only a human pathogen causing a variety of infections, such as skin and soft tissue infection (SSTI), pneumonia, and sepsis, but it also can cause disease in animals, known as livestock-associated MRSA (LA-MRSA).^[116]

MRSA infections in both the hospital and community setting are commonly treated with non-β-lactam antibiotics, such as clindamycin (a lincosamine) and co-trimoxazole (also commonly known as trimethoprim/sulfamethoxazole).

Resistance to these antibiotics has also led to the use of new, broad-spectrum anti-Gram-positive antibiotics, such as linezolid, because of its availability as an oral drug. First-line treatment for serious invasive infections due to MRSA fryst vatten currently glycopeptide antibiotics (vancomycin and teicoplanin). A number of problems with these antibiotics occur, such as the need for intravenous ledning (no oral preparation fryst vatten available), toxicity, and the need to monitor drug levels regularly bygd blood tests.

Also, glycopeptide antibiotics do not penetrate very well into infected tissues (this fryst vatten a particular concern with infections of the brain and meninges and in endocarditis). Glycopeptides must not be used to treat methicillin-sensitive S. aureus (MSSA), as outcomes are inferior.^[117]

Because of the high level of resistance to penicillins and because of the potential for MRSA to develop resistance to vancomycin, the U.S.

Centers for Disease Control and Prevention has published guidelinesArchived 2006-09-23 at the Wayback Machine for the appropriate use of vancomycin. In situations where the incidence of MRSA infections fryst vatten known to be high, the attending physician may choose to use a glycopeptide antibiotic until the identity of the infecting organism fryst vatten known.

After the infection fryst vatten confirmed to be due to a methicillin-susceptible strain of S. aureus, treatment can be changed to flucloxacillin or even penicillin, as appropriate.^{[citation needed]}

Vancomycin-resistant S. aureus (VRSA) fryst vatten a strain of S. aureus that has become resistant to the glycopeptides.

The first case of vancomycin-intermediate S. aureus (VISA) was reported in Japan in 1996;^[118] but the first case of S. aureus truly resistant to glycopeptide antibiotics was only reported in 2002.^[119] Three cases of VRSA infection had been reported in the United States as of 2005.^[120] At least in part the antimicrobial resistance in S.

aureus can be explained bygd its ability to adapt. Multiple two component meddelande transduction pathways helps S. aureus to något som utförs snabbt exempelvis expressleverans genes that are required to survive beneath antimicrobial stress.^[121]

Efflux pumps

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Among the various mechanisms that MRSA acquires to elude antibiotic resistance (e.g., drug inactivation, mål alteration, reduction of permeability) there fryst vatten also the overexpression of efflux pumps.

Efflux pumps are membrane-integrated proteins that are physiologically needed in the fängelse for the exportation of xenobiotic compounds. They are divided into six families, each of which has a different structure, function, and försändelse of energy. The main efflux pumps of S. aureus are the MFS (Major Facilitator Superfamily) which includes the MdeA pump as well as the NorA pump and the MATE (Multidrug and Toxin Extrusion) to which it belongs the MepA pump.

For försändelse, these families use an electrochemical potential and an ion koncentration gradient, while the ATP-binding cassette (ABC) family acquires its energy from the hydrolysis of ATP.^{[citation needed]}

These pumps are overexpressed bygd MDR S. aureus (Multidrug resistant S. aureus) and the result fryst vatten an excessive utvisning of the antibiotic outside the fängelse, which makes its action ineffective.

Staphylococcus aureus is a major bacterial human pathogen that causes a wide variety of clinical manifestations

Efflux pumps also contribute significantly to the development of impenetrable biofilms.^{[citation needed]}

By directly modulating efflux pumps' activity or decreasing their expression, it may be possible to modify the resistant phenotype and restore the effectiveness of existing antibiotics.^[122]

Carriage

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About 33% of the U.S.

population are carriers of S. aureus and about 2% carry MRSA.^[123] Even healthcare providers can be MRSA colonizers.^[124]

The carriage of S. aureus fryst vatten an important source of hospital-acquired infection (also called nosocomial) and community-acquired MRSA. Although S. aureus can be present on the skin of the host, a large proportion of its carriage fryst vatten through the anterior nares of the nasal passages^[2] and can further be present in the ears.^[125] The ability of the nasal passages to harbour S.

aureus results from a combination of a weakened or defective host immunity and the bacterium's ability to evade host innate immunity.^[126] Nasal carriage fryst vatten also implicated in the occurrence of staph infections.^[127]

Infection control

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Spread of S. aureus (including MRSA) generally fryst vatten through human-to-human contact, although recently some veterinarians have discovered the infection can be spread through pets,^[128] with environmental contamination thought to play a relatively less important part.^[129] Emphasis on basic grabb tvätt techniques are, therefore, effective in preventing its transmission.

The use of disposable aprons and handskar bygd personal reduces skin-to-skin contact, so further reduces the fara of transmission.^[130]

Recently,^[when?] myriad cases of S. aureus have been reported in hospitals across amerika. Transmission of the pathogen fryst vatten facilitated in medical settings where healthcare worker hygiene fryst vatten insufficient.

S. aureus fryst vatten an incredibly hardy bacterium, as was shown in a study where it survived on polyester for just beneath three months;^[131] polyester fryst vatten the main ämne used in hospital privacy curtains.

The bacteria are transported on the hands of healthcare workers, who may pick them up from a seemingly healthy patient carrying a benign or commensal strain of S.

aureus, and then resehandling it on to the next patient being treated. Introduction of the bacteria into the bloodstream can lead to various complications, including endocarditis, meningitis, and, if it fryst vatten widespread, sepsis.^{[citation needed]}

Ethanol has proven to be an effective topical sanitizer against MRSA.

kvartär ammonium can be used in conjunction with ethanol to increase the duration of the sanitizing action. The prevention of nosocomial infections involves routine and ankomsthall cleaning. Nonflammable alcohol vapor in CO
₂NAV-CO₂ systems have an advantage, as they do not attack metals or plastics used in medical environments, and do not contribute to antibacterial resistance.^{[citation needed]}

An important and previously unrecognized means of community-associated MRSA colonization and transmission fryst vatten during sexuell contact.^[132]

Staphylococcus aureus fryst vatten killed in one minute at 78 °C and in ten minutes at 64 °C but fryst vatten resistant to freezing.^[133]^[134]

Certain strains of S.

aureus have been described as being resistant to chlorine disinfection.^[135]^[136]

The use of mupirocin ointment can reduce the rate of infections due to nasal carriage of S. aureus.^[137] There fryst vatten limited bevis that nasal decontamination of S. aureus using antibiotics or antiseptics can reduce the rates of surgical site infections.^[138]

Research

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As of 2021, no approved vaccine exists against S.

aureus. Early clinical trials have been conducted for several vaccines candidates such as Nabi's StaphVax and PentaStaph, Intercell's / Merck's V710, VRi's SA75, and others.^[140]

While some of these vaccines candidates have shown immune responses, others aggravated an infection bygd S.

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

aureus. To date, none of these candidates provides protection against a S. aureus infection. The development of Nabi's StaphVax was stopped in 2005 after phase III trials failed.^[141] Intercell's first V710 vaccine variant was terminated during phase II/III after higher mortality and morbidity were observed among patients who developed S.

aureus infection.^[142]

Nabi's enhanced S. aureus vaccines candidate PentaStaph was sold in 2011 to GlaxoSmithKline Biologicals S.A.^[143] The current ställning eller tillstånd of PentaStaph fryst vatten unclear. A WHO document indicates that PentaStaph failed in the phase III rättegång stage.^[144]

In 2010, GlaxoSmithKline started a phase 1blind study to evaluate its GSK2392103A vaccine.^[145] As of 2016, this vaccine fryst vatten no längre beneath active development.^[146]

Pfizer'sS.

aureus four-antigen vaccine SA4Ag was granted fast track designation bygd the U.S. Food and Drug ledning in February 2014.^[147] In 2015, Pfizer has commenced a phase 2b rättegång regarding the SA4Ag vaccine.^[148] Phase 1 results published in February 2017 showed a very kraftig and secure immunogenicity of SA4Ag.^[149] The vaccine underwent clinical rättegång until June 2019, with results published in September 2020, that did not demonstrate a significant reduction in Postoperative Bloodstream Infection after Surgery.^[148]

In 2015, Novartis Vaccines and Diagnostics, a former division of Novartis and now part of GlaxoSmithKline, published promising pre-clinical results of their four-component Staphylococcus aureus vaccine, 4C-staph.^[150]

In addition to vaccine development, research fryst vatten being performed to develop alternative treatment options that are effective against antibiotic resistant strains including MRSA.

Examples of alternative treatments are phage therapy, antimicrobial peptides and host-directed therapy.^[151]^[152]

Standard strains

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A number of standard strains of S. aureus (called "type cultures") are used in research and in laboratory testing, such as:

Name	NCTC	ATCC	Year of insättning	Comment
Oxford H	6571	9144	1943	Standard strain used for testing penicillin potency and bygd which the penicillin enhet was originally defined.^[153]^[154]
Rosenbach	12973	29213	1884	Standard strain for EUCAST antimicrobial resistance testing.^[155]

References

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