Information about Staphylococcus Aureus

Staphylococcus aureus
Scientific classification
Domain: Bacteria Kingdom: Bacteria Phylum: Firmicutes Class: Cocci Order: Bacillales Family: Staphylococcaceae Genus: Staphylococcus Species: S. aureus
Binomial name
Staphylococcus aureus Rosenbach 1884

Staphylococcus aureus /ˌstæf.ə.loˈko.kəs ˈoɹˌi.əs/, literally "Golden Cluster Seed" and also known as golden staph, is the most common cause of staph infections. It is a spherical bacterium, frequently living on the skin or in the nose of a person, that can cause a range of illnesses from minor skin infections, such as pimples, impetigo, boils, cellulitis and abscesses, to life-threatening diseases, such as pneumonia, meningitis, endocarditis, Toxic shock syndrome (TSS), and septicemia. Abbreviated to S. aureus or Staph aureus in medical literature, S. aureus should not be confused with the similarly named (and also medically relevant) species of the genus Streptococcus.

S. aureus was discovered in Aberdeen, Scotland in 1880 by the surgeon Sir alexander ogston in pus from surgical abscesses.^[1] Each year some 500,000 patients in American hospitals contract a staphylococcal infection. ^[2]

Microbiology

S. aureus is a Gram-positive coccus, which appears as grape-like clusters when viewed through a microscope and has large, round, golden-yellow colonies, often with β-hemolysis, when grown on blood agar plates.^[3] The golden appearance is the etymological root of the bacteria's name: aureus means "golden" in Latin.

S. aureus is catalase positive and thus able to convert hydrogen peroxide (H₂O₂) to water and oxygen, which makes the catalase test useful to distinguish staphylococci from enterococci and streptococci. A large percentage of S. aureus can be differentiated from most other staphylococci by the coagulase test: S. aureus is primarily coagulase-positive, while most other Staphylococcus species are coagulase-negative.^[3] However, while the majority of S. aureus are coagulase-positive, some may be atypical in that they do not produce coagulase. Incorrect identification of an isolate can impact implementation of effective treatment and/or control measures.^[4] It is medically important to identify S.aureus correctly as S.aureus is much more aggressive and likely to be antibiotic-resistant. Coagulase-negative S. aureus appears to be an increasing problem that clinical laboratories should be aware of. They are as virulent as those producing coagulase and can colonize, cause infections and spread among patients.^[5]

S. aureus has about 2,600 genes and 2.8 million base pairs of DNA in its chromosome. Plasmids can also comprise part of the species' genome.

The species has been subdivided into two subspecies: S. aureus aureus and S. aureus anaerobius. The latter requires anaerobic conditions for growth, is an infrequent cause of infection, and is rarely encountered in the clinical laboratory.

Role in disease

S. aureus may occur as a commensal on human skin (particularly the scalp, armpits and groins); it also occurs in the nose (in about 25% of the population) and throat and less commonly, may be found in the colon and in urine. The finding of Staph. aureus under these circumstances does not always indicate infection and therefore does not always require treatment (indeed, treatment may be ineffective and re-colonisation may occur). It can survive on domesticated animals such as dogs, cats and horses, and can cause bumblefoot in chickens. It can survive for some hours on dry environmental surfaces, but the importance of the environment in spread of S. aureus is currently debated. It can host phages, such as the Panton-Valentine leukocidin, that increase its virulence.

S. aureus can infect other tissues when normal barriers have been breached (e.g. skin or mucosal lining). This leads to furuncles (boils) and carbuncles (a collection of furuncles). In infants S. aureus infection can cause a severe disease Staphylococcal scalded skin syndrome (SSSS).^[6]

S. aureus infections can be spread through contact with pus from an infected wound, skin-to-skin contact with an infected person, and contact with objects such as towels, sheets, clothing, or athletic equipment used by an infected person.

Deeply situated S. aureus infections can be very severe. Prosthetic joints put a person at particular risk for septic arthritis, and staphylococcal endocarditis (infection of the heart valves) and pneumonia, which may be rapidly fatal.

Staphylococcus aureus and influenza

S. aureus superinfection is an uncommon complication of influenza. However, in the last three influenza pandemics (1918, 1957–58, and 1968), added infection with S. aureus was a common complication.

Toxic Shock Syndrome

Certain strains of S. aureus are also the causative agent for Toxic Shock Syndrome.

Mastitis in cows

S. aureus is one of the causal agents of mastitis in dairy cows. Its large capsule protects the organism from attack by the cow's immunological defenses.^[7]

Virulence factors

Toxins

Depending on the strain, S. aureus is capable of secreting several toxins, which can be categorized into three groups. Many of these toxins are associated with specific diseases.

Pyrogenic toxin superantigens (PTSAgs) have superantigen activities that induce toxic shock syndrome (TSS). This group includes the toxin TSST-1, which causes TSS associated with tampon use. The staphylococcal enterotoxins, which cause a form of food poisoning, are included in this group.

Exfoliative toxins are implicated in the disease staphylococcal scalded-skin syndrome (SSSS), which occurs most commonly in infants and young children. The protease activity of the exfoliative toxins causes peeling of the skin observed with SSSS.

Staphylococccal toxins that act on cell membranes include alpha-toxin, beta-toxin, delta-toxin, and several bicomponent toxins. The bicomponent toxin Panton-Valentine leukocidin (PVL) is associated with severe necrotizing pneumonia in children. The genes encoding the components of PVL are encoded on a bacteriophage found in community-associated MRSA strains.

Role of pigment in virulence

The vivid yellow pigmentation of S. aureus may be a factor in its virulence. When comparing a normal strain of S. aureus with a strain modified to lack the yellow coloration, the pigmented strain was more likely to survive dousing with an oxidizing chemical such as hydrogen peroxide than the mutant strain was.

Colonies of the two strains were also exposed to human neutrophils. The mutant colonies quickly succumbed while many of the pigmented colonies survived. Wounds on mice were swiped with the two strains. The pigmented strains created lingering abscesses. Wounds with the unpigmented strains healed quickly.

These tests suggest that the yellow pigment may be key to the ability of S. aureus to survive immune system attacks. Drugs that inhibit the bacterium's production of the carotenoids responsible for the yellow coloration may weaken it and renew its susceptibility to antibiotics.^[8]

Diagnosis

Depending upon the type of infection present, an appropriate specimen is obtained accordingly and sent to the laboratory for definitive identification. A Gram stain is first performed to guide the way, which should show typical gram-positive bacteria, cocci, in clusters. Secondly, culture the organism in Mannitol Salt Agar, which is a selective medium with 7%-9% NaCl that allows S. aureus to grow producing yellow-colored colonies as a result of salt utilization and subsequet drop in the medium's pH. Furthermore, for differentiation on the species level, catalase (positive for all species), coagulase (fibrin clot formation), DNAse (zone of clearance on nutrient agar), lipase (a yellow color and rancid odor smell), and phosphatase (a pink color) tests are all done.

Treatment and antibiotic resistance

For more details on this topic, see Methicillin-resistant Staphylococcus aureus (MRSA).

Antibiotic resistance in S. aureus was almost unknown when penicillin was first introduced in 1943; indeed, the original petri dish on which Alexander Fleming observed the antibacterial activity of the penicillium mould was growing a culture of S. aureus. By 1950, 40% of hospital S. aureus isolates were penicillin resistant; and by 1960, this had risen to 80%.^[9]

Mechanisms of antibiotic resistance

Staphylococcal resistance to penicillin is mediated by penicillinase (a form of β-lactamase) production: an enzyme which breaks down the β-lactam ring of the penicillin molecule. Penicillinase-resistant penicillins such as methicillin, oxacillin, cloxacillin, dicloxacillin and flucloxacillin are able to resist degradation by staphylococcal penicillinase.

The mechanism of resistance to methicillin is by the acquisition of the mecA gene, which codes for an altered penicillin-binding protein (PBP) that has a lower affinity for binding β-lactams (penicillins, cephalosporins and carbapenems). This confers resistance to all β-lactam antibiotics and obviates their clinical use during MRSA infections.

Glycopeptide resistance is mediated by acquisition of the vanA gene. The vanA gene originates from the enterococci and codes for an enzyme that produces an alternative peptidoglycan to which vancomycin will not bind.

Staph infections lead to rapid weight loss and muscle depletion. Even after fully cured, it will still take months to recuperate fully.

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, due to a penicillinase (a form of β-lactamase). 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 S. aureus (MRSA) was reported in England.^[10]If the bacteria produces the enzymes β-lactamase or penicillinase, these enzymes will break open the β-lactam ring of the antibiotic, rendering the antibiotic ineffective

Despite this, MRSA generally remained an uncommon finding even in hospital settings until the 1990s when there was an explosion in MRSA prevalence in hospitals where it is now endemic.^[11]

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 lead 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 is currently glycopeptide antibiotics (vancomycin and teicoplanin). There are number of problems with these antibiotics, mainly centred around the need for intravenous administration (there is no oral preparation available), toxicity and the need to monitor drug levels regularly by means of blood tests. There are also concerns that glycopeptide antibiotics do not penetrate very well into infected tissues (this is a particular concern with infections of the brain and meninges and in endocarditis). Glycopeptides must not be used to treat methicillin-sensitive S. aureus as outcomes are inferior.^[12]

Because of the high level of resistance to penicillins, and because of the potential for MRSA to develop resistance to vancomycin, the Centers for Disease Control and Prevention have published guidelines for the appropriate use of vancomycin. In situations where the incidence of MRSA infections is known to be high, the attending physician may choose to use a glycopeptide antibiotic until the identity of the infecting organism is known. When the infection is confirmed to be due to a methicillin-susceptible strain of S. aureus, then treatment can be changed to flucloxacillin or even penicillin as appropriate.

Vancomycin-resistant S. aureus (VRSA) is 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;^[13] but the first case of S. aureus truly resistant to glycopeptide antibiotics was only reported in 2002.^[14] Three cases of VRSA infection have been reported in the United States.^[15] as of 2005.

Infection control

Spread of S. aureus (including MRSA) is through human-to-human contact, with environmental contamination thought to play a relatively unimportant part. Emphasis on basic hand washing techniques are therefore effective in preventing the transmission of S. aureus. The use of disposable aprons and gloves by staff reduces skin-to-skin contact and therefore further reduces the risk of transmission. Please refer to the article on infection control for further details.

Alcohol has proven to be an effective topical sanitizer against MRSA. Quaternary ammonium can be used in conjunction with alcohol to increase the duration of the sanitizing action. The prevention of nosocomial infections involve routine and terminal cleaning. Nonflammable alcohol vapor in CO₂ NAV-CO2 systems have an advantage as they do not attack metals or plastics used in medical environments, and do not contribute to antibacterial resistance.

An important and previously unrecognized means of community-associated methicillin-resistant S. aureus colonization and transmission is during sexual contact. ^[16]

Staff or patients who are found to carry resistant strains of S. aureus may be required to undergo "eradication therapy" which may include antiseptic washes and shampoos (such as chlorhexidine) and application of topical antibiotic ointments (such as mupirocin or neomycin) to the anterior nares of the nose.

March 2007: The BBC has reported promising experiments in UK where a vaporizer spraying some essential oils into the atmosphere reduced airborne bacterial counts by 90% and kept MRSA infections at bay. This may hold promise in MRSA infection control.

Footnotes