Staphylococci Overview and Virulence Factors

Staphylococci

• Staphylococci are gram-positive, spherical bacteria that often appear in grape-like clusters.
• They are facultative anaerobes, meaning they can thrive in the presence or absence of oxygen.
• They are resistant to heat and drying, making them capable of surviving for long periods on surfaces.
• Staphylococcus aureus is the most virulent species and is responsible for various infections, including food poisoning, toxic shock syndrome, and abscess formation.
• Staphylococcus epidermidis is less virulent and is often a cause of infections associated with implanted medical devices, such as catheters and prosthetics.
• Staphylococcus saprophyticus is known to cause urinary tract infections, particularly cystitis, in women.

Virulence Factors of Staphylococcus aureus

• Cell Wall Virulence Factors:

  • Capsule: Provides protection against phagocytosis.
  • Peptidoglycan: Plays a role in osmotic stability, triggers immune responses, and hinders phagocytosis.
  • Teichoic acid: Binds to fibronectin, promoting adherence.
  • Protein A: Binds to the Fc region of IgG, blocking opsonization and decreasing phagocytosis.
  • Fibronectin-binding protein (FnBP): Facilitates binding to mucosal cells and tissue matrix.
  • Clumping factor: Binds to fibrinogen, leading to coagulation and clumping.

• Enzymes:

  • Coagulase: Causes plasma to clot, potentially hindering phagocytosis.
  • Catalase: Converts hydrogen peroxide to water and oxygen, which helps neutralize reactive oxygen species.
  • Hyaluronidase: Degrades hyaluronic acid in connective tissues, facilitating bacterial spread.
  • Fibrinolysin (Staphylokinase): Dissolves fibrin clots, assisting in bacterial dissemination.
  • Lipases: Break down lipids, supporting survival in sebaceous areas.
  • Nuclease (DNAase): Degrades DNA, possibly aiding in bacterial spread and evasion of the host's immune response.

• Toxins:

  • Cytolytic exotoxins (α, β, γ, δ Toxins): Damage cell membranes, often referred to as hemolysins.
  • Panton-Valentine leukocidin: Lyses polymorphonuclear leukocytes (PMNs), contributing to virulence.
  • Superantigen exotoxins: Stimulate excessive T-cell activation, causing cytokine release and potentially leading to toxic shock syndrome.
    • Enterotoxins: Cause food poisoning upon ingestion.
    • Toxic shock syndrome toxin (TSST-1): The primary cause of toxic shock syndrome.
    • Exfoliatin (ET): Causes scalded skin syndrome in children by disrupting intercellular adhesion.

Clinical Significance of Staphylococcus aureus

• Infections often result from entry points such as skin breaks, wounds, and the respiratory tract.
• Localized infections typically present with inflammation, swelling, pus formation, and tissue necrosis.
• Food poisoning: Associated with the ingestion of enterotoxins produced by S. aureus.
• Toxic shock syndrome (TSS): Caused by the release of TSST-1, leading to systemic inflammation and multi-organ dysfunction.
• Scalded skin syndrome: Characterized by superficial blistering due to the action of exfoliatin, which disrupts skin layers.

Laboratory Identification of Staphylococci

• Gram stain: S. aureus appears as gram-positive cocci in clusters.
• Catalase test: Positive reaction (produces bubbles) distinguishes staphylococci from streptococci.
• Coagulase test: Positive for S. aureus, indicating the presence of coagulase.
• Mannitol salt agar (MSA): S. aureus ferments mannitol, producing yellow colonies, while other staphylococci typically form white colonies.
• Automated systems: Can provide rapid identification of staphylococcal species.

Treatment

• Serious infections: Require incision and drainage of localized lesions, plus systemic antibiotics.

Antibiotic Resistance and Methicillin-Resistant Staphylococcus aureus (MRSA)

• Penicillin resistance: Common due to staphylococcal production of penicillinase.
• Methicillin and oxacillin resistance (MRSA): Develops due to the acquisition of a gene coding for a new penicillin-binding protein (PBP-2a), rendering the bacteria resistant to beta-lactam antibiotics.
• Hospital-acquired MRSA (HA-MRSA): Frequently seen in healthcare settings, associated with longer hospital stays and higher mortality rates.
• Community-acquired MRSA (CA-MRSA): Increasingly reported in individuals without prior healthcare exposure.
• Vancomycin resistance: Emerged as a significant threat, leading to the use of alternative therapies like linezolid and daptomycin.

Prevention

• Infection control measures: Disinfection of hands and surfaces is crucial for limiting transmission.

Coagulase-Negative Staphylococci (CNS)

• Staphylococcus epidermidis: Primarily a component of the skin flora, but can cause infections associated with implanted devices, often due to its ability to form biofilms.
• Polysaccharide intracellular adhesin (PIA): Produced by S. epidermidis, facilitates adherence to implanted materials and forms a protective barrier against antimicrobial agents.

Staphylococci

• Gram-positive spherical bacteria, usually arranged in grapelike clusters
• Grow on various media, ferment carbohydrates, produce pigments (white to deep yellow)
• Found in human skin and mucous membranes
• Cause abscess formation, pyogenic infections, and septicemia

Staphylococcus aureus

• One of the most common causes of bacterial infections
• Responsible for food poisoning, toxic shock syndrome
• Virulence factors include capsule, peptidoglycan, teichoic acid, protein A, fibronectin-binding protein, clumping factor, enzymes, and toxins

Staphylococcus epidermidis

• Found in human skin
• Common cause of prosthetic implant infections

Staphylococcus saprophyticus

• Causes urinary tract infections, particularly cystitis in women
• Often referred to as Coagulase Negative Staphylococci (CNS)

Virulence Factors of Staphylococcus aureus

• Capsule: Helps bacteria resist phagocytosis
• Peptidoglycan: Induces inflammation, attracts leukocytes, inhibits phagocytosis
• Teichoic acid: Binds to fibronectin
• Protein A: Binds to IgG, hindering phagocytosis
• Fibronectin-binding protein: Promotes binding to mucosal cells and tissue matrix
• Clumping factor: Binds to fibrinogen, causing bacteria to clump

Enzymes of Staphylococcus aureus

• Coagulase: Causes plasma to clot by activating prothrombin
• Catalase: Converts hydrogen peroxide to water and oxygen
• Hyaluronidase: Breaks down hyaluronic acid, allowing bacteria to spread
• Fibrinolysin: Dissolves fibrin clots
• Lipases: Hydrolyze lipids, enabling bacteria to survive in sebaceous areas
• Nuclease (DNAase): Degrades DNA, which is implicated in its virulence

Toxins of Staphylococcus aureus

• Cytolytic exotoxins (α, β, γ, δ Toxins): Damage cell membranes, including red blood cells
• Panton-Valentine leukocidin:: Lyses leukocytes, increasing strain virulence
• Superantigen exotoxins: Bind to T-cell receptors, causing enhanced T-cell response
• Enterotoxins: Contaminate food and cause staphylococcal gastroenteritis
• Toxic shock syndrome toxin (TSST-1): Cause of toxic shock syndrome
• Exfoliatin (ET): Causes scalded skin syndrome in children, disrupting skin cohesion

Clinical Significance of Staphylococcus aureus Infections

• Localized Skin Infections: Folliculitis, furuncles (boils), carbuncles, impetigo
• Deep Localized Infections: Osteomyelitis, septic arthritis
• Septicemia: Presence of bacteria in the bloodstream
• Acute Endocarditis: Caused by contaminated injections or needles
• Pneumonia: Can be severe and necrotizing
• Nosocomial Infections: Common in hospitals, affecting wounds and catheters
• Toxinoses: Diseases caused by bacterial toxins (Toxic shock syndrome, staphylococcal gastroenteritis)

Antibiotic Resistance in Staphylococcus aureus

• Methicillin-resistant Staphylococcus aureus (MRSA): Resistant to beta-lactam antibiotics (penicillin, methicillin) due to altered penicillin-binding protein (PBP-2a)

Community-Acquired MRSA (CA-MRSA)

• Occurs in individuals without previous risk factors for MRSA infections
• Causes skin and soft tissue infections (abscesses, cellulitis)

Vancomycin Resistance

• Vancomycin was a treatment for MRSA but resistance has emerged

Prevention of Staphylococcus aureus Infections

• No effective vaccine
• Disinfection of hands and fomites to control nosocomial outbreaks

Coagulase-Negative Staphylococci (CNS)

• Staphylococcus epidermidis
• Important cause of hospital-acquired infections associated with implanted devices and catheters
• Produces polysaccharide intercellular adhesin, aiding adherence to bioprosthetic materials.

Staphylococcus

• Gram-positive spherical bacteria
• Occur in grape-like clusters
• Facultatively anaerobic
• Produce catalase
• Common in skin and mucous membranes

Staphylococcus aureus

• Most virulent species of Staphylococcus
• Produces coagulase, an enzyme that clots plasma
• Common cause of bacterial infections
• Causes food poisoning and toxic shock syndrome

Staphylococcus epidermidis

• Less virulent than S. aureus
• Common cause of prosthetic implant infections

Staphylococcus saprophyticus

• Less virulent than S. aureus
• Causes urinary tract infections, especially cystitis in women

Virulence Factors of S. aureus

• Hyaluronidase (spreading factor): Degrades hyaluronic acid in connective tissues, promoting spread of bacteria
• Fibrinolysin (staphylokinase): Dissolves fibrin clots
• Lipases: Hydrolyze lipids, aiding survival in sebaceous areas
• Nuclease (DNAase): Degrades DNA

Toxins of S. aureus

• Cytolytic Exotoxins (α, β, γ, δ): Damage mammalian cell membranes, including red blood cells
• Panton-Valentine Leukocidin: Lyses neutrophils (PMNs), increasing virulence
• Superantigen Exotoxins: Bind to T-cell receptors and MHC Class II, triggering excessive T-cell activation
  • Toxic shock syndrome toxin (TSST-1): Causes toxic shock syndrome (TSS), leading to high fever, rash, vomiting, diarrhea, hypotension, and organ damage
  • Exfoliatin (ET): Causes scalded skin syndrome in children, destroying skin intercellular adhesive
• Enterotoxins: Produced by around half of S. aureus isolates
  • Contaminate food and cause food poisoning upon ingestion, leading to nausea, vomiting, and diarrhea

Clinical Significance of S. aureus

• Infection causes inflammation, pus formation, and tissue necrosis
• Can invade bloodstream, causing bacteremia and septicemia
• May result in internal abscesses, skin lesions, and infections in various organs

Localized S. aureus Infections

• Folliculitis: Small abscesses involving hair follicles
• Furuncles (boils): Subcutaneous abscesses forming around foreign bodies
• Carbuncles: Large, deep, multiloculated skin infections
• Impetigo: Superficial, spreading, crusty skin lesions, common in children

Other S. aureus Infections

• Deep, localized infections: May be metastatic from superficial infections or result from trauma
• Acute endocarditis: Caused by contaminated injections or needles
• Septicemia: Generalized infection
• Pneumonia: Can cause severe, necrotizing pneumonia
• Healthcare-associated infections (nosocomial): Significant cause of hospital-acquired infections

Laboratory Identification

• Gram staining: Strongly gram-positive bacteria, often in clusters
• Catalase test: Positive
• Coagulase test: Positive in S. aureus, negative in coagulase-negative staphylococci (CNS)
• Mannitol fermentation: Positive in S. aureus

Treatment

• Incision and drainage: for localized lesions
• Systemic antibiotics: Choice is complex due to frequent antibiotic resistance
• Penicillin G: No longer the first-line treatment due to widespread penicillinase resistance
• β-Lactamase-resistant penicillins: Methicillin or oxacillin
• Methicillin-resistant S. aureus (MRSA): Resistant to many β-lactam antibiotics

MRSA

• Hospital-acquired MRSA (HA-MRSA): Common in hospital settings
• Community-acquired MRSA (CA-MRSA): Infections occur independent of hospital exposure
• Vancomycin resistance: Emergence of vancomycin-resistant MRSA strains, prompting alternative therapies

Coagulase-Negative Staphylococci (CNS)

• Important agents of healthcare-associated infections
• Infections associated with implanted prosthetic devices and catheters

Staphylococcus epidermidis

• Part of normal skin flora
• Common cause of infections of implants, such as heart valves and catheters
• Produces polysaccharide intercellular adhesin (PIA), facilitating adherence to biomaterials

Prevention

• No effective S. aureus vaccine
• Infection control measures: Hand washing, disinfection of surfaces, and fomites

Staphylococci

• Staphylococci are Gram-positive spherical bacteria, often arranged in grape-like clusters.
• They are commonly found on skin and mucous membranes.
• Staphylococci can cause a range of infections, from minor skin infections to life-threatening sepsis.

Important Species

• The most clinically significant species are Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus saprophyticus.
• S. aureus is a major cause of bacterial infections, food poisoning, and toxic shock syndrome.
• S. epidermidis is often involved in prosthetic implant infections.
• S. saprophyticus is a frequent cause of urinary tract infections, particularly in women.

General Features

• Staphylococci are facultatively anaerobic, meaning they can grow with or without oxygen.
• They are catalase-positive, which distinguishes them from streptococci.
• S. aureus is the most virulent species and almost always produces coagulase, an enzyme that clots plasma.
• Coagulase-negative staphylococci (CNS) are less virulent and lack coagulase.

Staphylococcus aureus

• S. aureus infections often require a compromised host, like a skin break, foreign body insertion, or weakened immune system.
• S. aureus can cause infections through direct invasion, toxin production, or a combination of both.

Epidemiology

• S. aureus is commonly carried by healthy individuals on their skin and mucous membranes, making them potential carriers.
• Transmission can occur through direct contact, contaminated fomites, or contaminated food.

Pathogenesis

• S. aureus virulence depends on various factors that contribute to its ability to cause disease.
• Virulence factors include:

Cell Wall Virulence Factors

• Capsule: A thin polysaccharide layer that can hinder phagocytosis.
• Peptidoglycan: Provides structural support, stimulates inflammation, attracts leukocytes (contributes to abscess formation), and can inhibit phagocytosis.
• Teichoic acid: Binds to fibronectin, a protein found in connective tissue.
• Protein A: Binds to the Fc region of IgG antibodies, interfering with opsonization and phagocytosis.
• Fibronectin-binding protein: Promotes attachment to mucosal cells and tissue matrix.
• Clumping factor: Binds to fibrinogen, converting it to fibrin and causing staphylococci to clump together.

Enzymes

• Coagulase: Clots plasma by activating prothrombin, potentially aiding in evading phagocytosis.
• Catalase: Converts hydrogen peroxide (H2O2) to water and oxygen, detoxifying reactive oxygen species.

Infections Caused by Staphylococcus aureus

• Localized Skin Infections:

  • Folliculitis: Small abscesses in hair follicles.
  • Furuncles (Boils): Subcutaneous abscesses often forming around foreign bodies (e.g., splinters).
  • Carbuncles: Larger, deeper, multiloculated skin infections that can lead to bacteremia.
  • Impetigo: Superficial, spreading, crusty skin lesions often seen in children.

• Deep, Localized Infections:

  • Osteomyelitis: Infection of bone marrow.
  • Septic Arthritis: Acute infection of joint space, particularly in children.

• Acute Endocarditis: Infection of the heart valves, often caused by contaminated injections or needles.

• Septicemia: Generalized infection with sepsis, potentially fatal.

• Pneumonia: Severe, necrotizing pneumonia.

• Nosocomial Infections: Hospital-acquired infections, frequently associated with wounds or catheters.

• Toxinoses: Disease caused by toxins:

  • Toxic Shock Syndrome (TSS): High fever, rash, vomiting, diarrhea, hypotension, and multiorgan damage.
  • Staphylococcal Gastroenteritis: Food poisoning caused by ingesting enterotoxin-producing S. aureus. Symptoms include nausea, vomiting, and diarrhea, onset within hours of ingestion.
  • Scalded Skin Syndrome: Superficial blistering caused by an exfoliative toxin that disrupts skin layers, resulting in peeling.

Laboratory Identification

• Microscopically, S. aureus appears as Gram-positive cocci in grape-like clusters.
• Catalase Test: Positive (distinguishes from streptococci).
• Coagulase Test: Positive (distinguishes from most coagulase-negative staphylococci).
• Mannitol Fermentation: Positive (distinguishes from most coagulase-negative staphylococci).
• Automated systems like VITEK can aid in rapid identification.

Treatment

• Serious S. aureus infections: Require aggressive management with incision and drainage of abscesses and systemic antibiotics.
• Antibiotic Resistance: S. aureus frequently develops antibiotic resistance, including penicillinase production, methicillin resistance, and vancomycin resistance.

Methicillin-Resistant Staphylococcus aureus (MRSA)

• Hospital-Acquired MRSA (HA-MRSA): Common in hospitals, often resistant to many antibiotics, including methicillin and oxacillin.
• Community-Acquired MRSA (CA-MRSA): Emerged in the mid-1990s, occurring in individuals with no previous hospital exposure. Most often causes skin and soft tissue infections, but can cause severe diseases like pneumonia, osteomyelitis, and septicemia.

Vancomycin Resistance

• Vancomycin-Resistant S. aureus (VRSA): Emerged in 1997, prompting the use of alternative antibiotics like linezolid and daptomycin.

Prevention

• No effective vaccine against S. aureus.
• Infection control procedures like hand hygiene and disinfection of fomites are critical for preventing the spread of S. aureus.

Coagulase-Negative Staphylococci (CNS)

• CNS are often involved in hospital-acquired infections, primarily related to implanted prosthetic devices and catheters.
• Staphylococcus epidermidis: Commonly found on skin and can cause infections like prosthetic valve and catheter infections.
• Polysaccharide Intercellular Adhesin: Produced by S. epidermidis, facilitating adherence to prosthetic surfaces and acting as a barrier to antibiotics.

This quiz delves into the characteristics and virulence factors of Staphylococci, particularly focusing on Staphylococcus aureus and its role in various infections. Test your knowledge on the different species and their implications in medical contexts.