Pathophysiology of Staphylococcus aureus, epidermidis, and saprophyticus

Complete explanation of the pathophysiology of S. aureus, epidermidis, and saprophyticus

Subjects: Microbiology · Systems: Pathology, Microbiology · Tags: Microbiology

There are two main ways it can cause damage:

Biofilm (Exopolysaccharide Layer)

Staphylococcus aureus is part of the normal skin flora. Imagine you are going to perform a vein puncture. Some of the S. aureus can enter the bloodstream, while others may remain on the catheter. Once in these locations, the bacteria begin to secrete a polysaccharide layer around themselves, forming a biofilm. This layer allows the bacteria to communicate with each other and coordinate their behavior. Additionally, the thick polysaccharide layer protects the bacteria from both immune cells and antibiotics, making these infections difficult to treat. Biofilms are particularly relevant in the context of catheters and other catheter-associated infections.

Exotoxins

Toxic Shock Syndrome Toxin-1 (TSST-1)

When S. aureus enters the body, it can produce TSST-1, a toxin that functions as a superantigen. This means it binds directly to MHC class II molecules on antigen-presenting cells and bridges them to T-cell receptors. This nonspecific activation of T cells hyper-stimulates the immune system, leading to a massive release of cytokines and interleukins. The inflammatory reaction that follows has several key effects: the cytokines act on the skin, causing a widespread rash; they increase capillary permeability, which can lead to hypotension; and they act on the hypothalamus, producing fever. These combined effects result in toxic shock syndrome.

Leukocidins

Leukocidins are toxins that form pores in specific leukocytes, causing leakage of ions and other intracellular components. The death of these immune cells leads to tissue necrosis and triggers a strong inflammatory response. When leukocidins act in the lungs, they can cause parenchymal tissue necrosis, a condition known as necrotizing pneumonia.

Exfoliative Toxins

Exfoliative toxins specifically target keratinocytes. These cells are connected by desmosomes, which contain desmoglein-1. The toxin destroys desmoglein-1, breaking the connections between keratinocytes. As a result, the cells cannot stick together, forming blisters. These blisters eventually separate from the skin, causing extensive skin loss. This condition is most common in children under six years old and is seen in Staphylococcal Scalded Skin Syndrome (SSSS).

Hemolysin (Beta-Hemolysin)

Beta-hemolysin destroys the membranes of red blood cells, releasing hemoglobin, which is subsequently broken down. This process of red blood cell destruction can be observed in the laboratory using a blood agar plate. When S. aureus produces beta-hemolysin, clear zones appear around the colonies, indicating hemolysis and helping identify the bacteria.

Enterotoxins

Enterotoxins target enterocytes in the gastrointestinal tract. They produce pores in the cell membrane, leading to ion leakage and loss of cellular function, particularly absorption. This causes electrolyte imbalances and diarrhea, resulting in gastroenteritis. Symptoms typically appear less than six hours after ingestion of contaminated food, commonly mayonnaise or protein-rich foods.

Pathophysiology of S. Epidermidis

S. epidermidis is also part of the normal skin flora. Its main pathogenic mechanism is biofilm formation. By creating a polysaccharide layer, it protects itself from the immune system and communicates with other bacteria. Biofilms frequently form on vascular devices, urinary catheters, and prosthetic devices such as heart valves and joints. When a device is inserted, the skin barrier is breached, providing the bacteria a way in. Similarly, during prosthetic surgery, opening the body can allow S. epidermidis to contaminate the prosthesis. Once established, biofilms contribute to persistent infections that are challenging to treat.

Pathophysiology of Staphylococcus Saprophyticus

S. saprophyticus can cause disease through biofilm formation, like the other staphylococci, but also through the action of urease. For instance, when a catheter is placed in the urinary tract, bacteria from the skin may be introduced. Urease breaks down urea into carbon dioxide and ammonia. Ammonia is basic, so it raises the pH of the urine. Higher pH favors bacterial growth, as they thrive in less acidic environments. Additionally, ammonia can combine with urinary salts such as magnesium and sulfate to form struvite crystals, which may lead to urinary stones and obstruction.

Catheters are one way bacteria can enter the urinary tract, but they are not the only route. Poor hygiene, such as wiping from back to front in females, can transfer bacteria from the perineum near the urethra. Once in the urinary tract, the combination of urease activity and crystal formation can lead to blockage and infection.

Clinical Features of Staphylococcus Aureus

S. aureus infections often begin in the skin and soft tissues. When the skin barrier is breached and the bacteria gain access to deeper tissues, a strong immune response ensues. White blood cells infiltrate the area, causing inflammation, redness, pain, and pus formation. For example, inflammation around a hair follicle can produce a furuncle, and multiple furuncles merging together form a carbuncle. If the infection involves only the epidermis, it may present as impetigo, whereas involvement of the dermis produces cellulitis. Accumulation of pus in tissues results in an abscess. In more severe cases, bacteria may spread to the muscle, causing pyomyositis, or to bone tissue, leading to osteomyelitis. Infection of the joint can result in septic arthritis.

S. aureus can also enter the bloodstream, causing bacteremia. Bacteremia may be asymptomatic but can progress to septicemia, with systemic signs of infection. Hematogenous spread allows the bacteria to reach distant organs, including the meninges, leading to meningitis, or the brain, causing brain abscesses. Spread to the lungs can result in pneumonia, especially in elderly patients or following influenza. The heart valves are also susceptible, and bacterial colonization can lead to infective endocarditis.

Pearl:
In elderly patients, pneumonia caused by S. aureus is commonly found after an infection by a flu.

Exotoxins contribute further to clinical disease. TSST-1 can cause toxic shock syndrome, while exfoliative toxins destroy desmoglein-1, leading to keratinocyte separation, inflammation, blistering, and a positive Nikolsky sign, characteristic of staphylococcal scalded skin syndrome (SSSS). Enterotoxins can damage the gastrointestinal lining, impairing absorption and causing electrolyte imbalances, which manifests as diarrhea, commonly seen in foodborne gastroenteritis.

Risk factors for invasive S. aureus infection include intravenous drug use, surgical procedures, and the presence of foreign bodies such as catheters or prosthetic devices. Understanding these mechanisms is critical for anticipating clinical presentations and guiding treatment strategies.

Clinical Features of Staphylococcus Epidermidis

S. epidermidis has the ability to travel into the bladder from the perineum, and cause infections of the bladder, and potentially, spread into the urethers, into the kidneys, leading to urinary tract infections (U.T.I’s).

Treatment

Treatment of Staphylococcus aureus

Methicillin-Sensitive Staphylococcus aureus (MSSA)

Some strains of S. aureus produce β-lactamase, an enzyme that inactivates penicillin. However, they remain sensitive to penicillinase-resistant β-lactams, particularly oxacillin and nafcillin. These are the drugs of choice for MSSA infections.

Recommended therapy for MSSA:

Methicillin-Resistant Staphylococcus aureus (MRSA)

Resistance arises from the mecA gene, which encodes an altered penicillin-binding protein (PBP2a). This protein has low affinity for β-lactam antibiotics, including methicillin and its derivatives, rendering them ineffective.

Two clinically relevant forms exist:

Recommended therapy for MRSA:

Vancomycin-Resistant Staphylococcus aureus (VRSA)

Rare strains acquire the vanA gene (often from Enterococcus), which alters the peptidoglycan structure and prevents vancomycin binding. These strains are highly resistant and require alternative agents.

Recommended therapy for VRSA:

Treatment of Staphylococcus epidermidis

S. epidermidis shares resistance mechanisms with S. aureus.

A key clinical distinction is that many S. epidermidis infections are associated with foreign bodies (e.g., catheters, prosthetic joints, prosthetic valves). In catheter-associated infections, removing the device is often sufficient and preferred over prolonged antibiotic therapy.

Recommended therapy for S. epidermidis:

Treatment of Staphylococcus saprophyticus

S. saprophyticus primarily causes urinary tract infections, especially cystitis in young women. It remains sensitive to most urinary antibiotics, and treatment follows the same principles as uncomplicated cystitis caused by E. coli.

First-line therapy:

Alternative options (if contraindications to first-line agents):

Disclaimer: For education only. Not medical advice; always follow your institution's guidance.