Introduction to Staphylococcus aureus:
- Staphylococci are spherical shaped Gram-positive grape-like cluster forming bacteria. They are non-motile, non-spore former and occasionally capsulated.
- If capsule is present, it is very thin (microcapsule).
- They are widespread in nature; their natural habitat being skin and mucous membrane of mammals
- Staphylococcus aureus, S. saprophyticus and S. epidermidis are some medically important species of Staphylococcus.
- S. aureus can cause both superficial and deep pyogenic infections as well as a number of toxin mediated illness
- The coagulase negative S. saprophyticus is an important cause of UTI in women of child bearing age. It may cause septicemia, endocarditis in patients with cardiac surgery
- Similarly, S. epidermidis which is a universal skin commensal sometime may act as opportunistic pathogen in patients having prosthetic devices, intraperitoneal catheters and may lead to septicemia and endocarditis
- Cultural Characteristics of S. aureus:
- They are facultatively anaerobes.
- They grow within a temperature range 10-42 °C, optimal temperature being 37 °C (pH=7.4-7.6)
- On nutrient agar plate, the colonies after 18-24hr of aerobic incubation are large (2-4mm diameter), round, smooth, raised, shiny, opaque and often pigmented
- Most strains of S. aureus form deep golden yellow pigment or some may produce creamy orange or yellow pigment. Pigment production is best seen when grown aerobically at temperature 20-25 °C
- In liquid media, S. aureus produces turbidity but no production of pigmentation
- On Blood agar, it produces similar colonies as a nutrient agar. However, some strains produce β-hemolysis on blood agar
- On MacConkey agar (without Crystal Violet), the colonies are pin head, 0.1-0.5mm in diameter after 18-24hr of aerobic incubation at 37 °C. They are lactose fermenters and produce pink colonies on MA
- S. aureus ferment mannitol as well as it can tolerate high salt concentration (9-10%) and hence on selective medium like Mannitol Salt Agar (MSA) which contain 1% mannitol, 7.5% NaCl with phenol red as indicator, it forms approx. 1 mm diameter yellow colonies surrounded by yellow medium due to acid formation.
Biochemical Properties of Staphylococcus aureus:
- They are catalase positive.
- Coagulase production is the most identifying characteristics of S. aureus which differentiates it form other species of Staphylococci. It gives both tube test (free coagulase) and Slide test (bound coagulase) positive
- Based on coagulase production, Staphylococci are divided into two groups i.e.
- Coagulase positive: S. aureus, S. intermidis, S. hyicus, S. delphi, S. schleiferi subsp coagulans
- Coagulase negative: S. epidermis, S. saprophyticus, S. haemolyticus
- S. aureus ferments a range of sugars- Mannitol, Trehalose, Sucrose, Maltose with acid production but no gas.
- S. aureus gives acetoin production as well as alkaline phosphatase test
- S. aureus also produces DNase enzyme as well as give positive catalase test
Virulence Factors of S. aureus:
Surface Proteins and Adhesins
S. aureus produces several surface proteins such as fibrin-binding proteins that facilitate attachment to tissues and blood clots. Some strains that cause osteomyelitis and septic arthritis also possess collagen-binding adhesins. Additionally, teichoic acids—composed of ribitol-5-phosphate polymers—play a key role in adherence to mucosal epithelial cells.
Invasins and Enzymes
- These include enzymes like staphylokinase, hyaluronidase, lipase, and DNase.
- Staphylokinase acts as a plasminogen activator, breaking down fibrin clots (fibrinolysin activity), thereby aiding bacterial spread through tissues.
- Hyaluronidase degrades hyaluronic acid in the host’s connective tissue, enabling the organism to move from a localized site to surrounding areas.
- DNase mainly serves to provide nutrients by breaking down DNA from dead cells. Although it plays a minor role in disease progression, it may assist bacterial spread by reducing the viscosity caused by extracellular DNA.
Surface Factors (Capsule and Protein A)
Capsular Polysaccharides
Some S. aureus strains possess a surface capsule distinct from the polysaccharides involved in adhesion or biofilm formation. While its exact role in virulence remains uncertain, the capsule contributes to resistance against phagocytosis.
Protein A
Found in over 90% of S. aureus strains, Protein A is covalently attached to the peptidoglycan layer. It binds to the Fc region of IgG antibodies at their complement-binding sites, blocking complement activation. This prevents C3b formation, reducing opsonization and protecting the bacteria from phagocytosis.
Catalase Production
Catalase decomposes hydrogen peroxide (H₂O₂) into water and oxygen. Since H₂O₂ is a toxic molecule generated by phagocytes during phagolysosome formation, catalase enables S. aureus to survive the oxidative burst inside immune cells.
Coagulase Production
Although coagulase is primarily a diagnostic enzyme, it also aids pathogenesis by clotting plasma. This clot formation walls off the infection site, hindering neutrophil migration and allowing the bacteria to persist locally.
Membrane-Damaging Toxins
α-Toxin
The most potent and well-studied cytolytic toxin of S. aureus, α-toxin forms pores in host cell membranes, leading to leakage of small molecules and cell death.
β, γ, and δ Toxins
Other strains produce these toxins, which can disrupt the membranes of various cell types, not just red blood cells.
Leukocidin
A bi-component toxin that acts synergistically to damage leukocyte membranes, contributing to immune evasion.
Exotoxins
Enterotoxins
S. aureus can produce seven antigenic types of enterotoxins—A, B, C₁, C₂, C₃, D, and E. Enterotoxin A is particularly significant and acts as a superantigen. When ingested, it causes vomiting and diarrhea, leading to staphylococcal food poisoning.
Toxic Shock Syndrome Toxin (TSST-1)
The principal toxin responsible for toxic shock syndrome. TSST-1 acts as a superantigen, triggering non-specific T-cell activation and excessive cytokine release (IL-1, IL-2, TNF-α) into the bloodstream, resulting in systemic inflammation and shock.
Exfoliative Toxins
These toxins are associated with Staphylococcal Scalded Skin Syndrome (SSS). They function as epidermolytic proteases that cleave desmoglein, a cell adhesion molecule, leading to separation of the epidermal layers.