Gram Positive Cocci

Etymology

• “staphylo-” → from Greek staphylē = “bunch of grapes” 🍇

• “-coccus” → from Greek kokkos = “berry” or “round grain”

👉 So literally:
“grape-like clusters of round bacteria”

Staphylococcus =
A genus of Gram-positive, spherical (cocci) bacteria that:

• Appear in grape-like clusters under the microscope

• Are commonly found on skin and mucous membranes

• Are catalase-positive (helps distinguish from Streptococcus)

• Can be aerobic or facultative anaerobes

• Some species are normal flora, while others cause infections (e.g., skin infections, abscesses)

Key Species (with meaning)

• Staphylococcus aureus

  • aureus = Latin “golden” → forms gold-colored colonies

• Staphylococcus epidermidis

  • epidermidis = “of the skin” → normal skin flora

• Staphylococcus saprophyticus

  • saprophyticus = “feeding on dead/organic matter

Clinical Features (from your slide, explained)

1. Purulent skin infections

• Folliculitis → infection of hair follicles

• Impetigo → superficial skin infection (often honey-colored crusts)

• Carbuncles → deeper, connected abscesses
  👉 Mostly caused by S. aureus

2. UTI

• Commonly caused by S. saprophyticus
  👉 Especially in young sexually active women

3. Opportunistic / Hospital-acquired infections

• Seen in hospitalized or immunocompromised patients
  👉 Often S. epidermidis (less virulent but opportunistic)

4. Systemic diseases

• Pneumonia

• Bacteremia (bacteria in blood)

• Wound infections
  👉 Mainly S. aureus → more aggressive

Folliticulis: S. aureus

Etymology

• “follicul-” → from Latin folliculus = “small bag” or “sac” (hair follicle)

• “-itis” → Greek = “inflammation”

Folliculitis = inflammation of a hair follicle

Common Causes

• Most common: Staphylococcus aureus

why?

Step-by-Step Mechanism 1. Normal colonizer of skin

• S. aureus commonly lives on:

  • Skin

  • Nose (nares)
    👉 So it’s already in the right place

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2. Entry into hair follicle

• Hair follicles are natural openings in the skin

• Entry is easier when:

  • Shaving (micro-cuts)

  • Friction (tight clothes)

  • Sweat/occlusion

👉 Bacteria get trapped inside the follicle

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3. Adhesion + colonization

• S. aureus has adhesins (surface proteins) that stick to:

  • Keratin

  • Extracellular matrix

👉 Helps it anchor inside the follicle

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4. Virulence factors → tissue damage

S. aureus produces:

• Coagulase → forms fibrin “shield” (hides from immune system)

• Cytotoxins (e.g., leukocidins) → kill immune cells

• Enzymes → break down tissue

👉 This allows local invasion and survival

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5. Strong neutrophil response → PUS

• Immune system sends neutrophils

• Bacteria + dead neutrophils + debris = pus

👉 That’s why folliculitis looks like:

• Small pustules centered on hair

Opportunistic / Hospital-acquired infections

• Seen in hospitalized or immunocompromised patients
  👉 Often S. epidermidis (less virulent but opportunistic)

2. UTI

• Commonly caused by S. saprophyticus
  👉 Especially in young sexually active women

Because S. saprophyticus colonizes the genital/perineal area, adheres strongly to the urinary tract, and is mechanically introduced into the bladder during sexual activity.

Step-by-step explanation 1. Normal colonization near the urethra

• S. saprophyticus lives in:

  • Perineum (skin around genitals)

  • Vaginal flora

👉 So it’s already right next to the urethral opening

2. Female anatomy = short urethra

• Female urethra is:

  • Short (~4 cm)

  • Close to vagina + anus

👉 Bacteria have a very short distance to reach the bladder

3. Sexual activity = mechanical transfer

• During intercourse:

  • Bacteria are pushed into the urethra

👉 This is why UTIs are sometimes called:

• “Honeymoon cystitis”

α-toxin (most high-yield)

a-toxin (alpha-toxin) is named for being the first of several hemolysins identified from Staphylococcus aureus.

Mechanism: Forms pores in cell membranes

Effects:

• Damages:

  • RBCs

  • WBCs

  • Platelets

• Disrupts smooth muscle in blood vessels

• Causes:

  • Tissue necrosis

  • Severe local damage

👉 Think: “punches holes in cells → everything leaks out → cell dies”

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⚠ β-toxin

• Works with α-toxin

• Enhances tissue destruction

β-toxin = “the second classified toxin” produced by the bacterium

• The Greek letters (α, β, γ, δ) are just a naming system, not describing structure directly

• So β-toxin literally means: “the second toxin (poison) identified in this group

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Why this matters clinically

These toxins explain why S. aureus causes:

• Pus (kills neutrophils)

• Abscesses (localized destruction)

• Necrotic skin infections

• “leuko-” → from Greek leukos = “white”

• “-cidin” → from Latin caedere = “to kill”

👉 Leukocidin = “white cell killer”

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Definition

Leukocidins are exotoxins produced by Staphylococcus aureus that:

• Kill white blood cells (especially neutrophils and macrophages)

• Work by:

  • Forming pores in cell membranes

  • Increasing permeability → cells swell and burst

1. Pyrogenic

• “pyro-” → Greek pyr = fire 🔥

• “-genic” → “producing”

👉 Pyrogenic = “fever-producing”

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2. Toxin

• From Greek toxikon = poison (originally arrow poison)

👉 Toxin = a poisonous substance produced by organisms

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3. Superantigen

• “super-” = excessive / above normal

• “antigen” = substance that stimulates immune response

👉 Superantigen = an antigen that overstimulates the immune system

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Definition

Pyrogenic toxin superantigens (PTSAgs) are exotoxins produced by Staphylococcus aureus that:

👉 Massively activate the immune system in a non-specific way, causing:

• Widespread T-cell activation

• Huge cytokine release (cytokine storm)

• Fever and systemic inflammation

Exfoliative

• “ex-” = out / away

• “folium” (Latin) = leaf

👉 Exfoliate = “to peel off like leaves”

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2. Toxin

• From Greek toxikon = poison

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3. Exfoliatin / Epidermolytic

• “epidermo-” = epidermis (outer skin layer)

• “-lytic” = breaking

👉 Epidermolytic toxin = “breaks the outer skin layer”

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Definition

Exfoliative toxin (A & B) is an exotoxin produced by Staphylococcus aureus that:

👉 Acts as a protease to:

• Break down proteins that hold skin cells together

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🔬 Mechanism (HIGH-YIELD)

• Targets desmoglein-1 (cell adhesion protein in epidermis)

• Causes:

  • Separation of epidermal layers

  • Skin cells lose attachment → peeling

👉 Think:
“cuts the glue between skin cells”

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⚠ Types (from your slide)

• ET-A

  • Heat (thermo) stable

  • Chromosome-encoded

• ET-B

  • Heat labile

  • Plasmid-encoded

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🩺 Clinical Effect Staphylococcal Scalded Skin Syndrome (SSSS)

• Skin looks like it’s been burned/scalded

• Features:

  • Blistering

  • Peeling (exfoliation)

  • Positive Nikolsky sign (skin slips off easily)

• Most common in:

  • Infants

Toxic-Shock-Syndrome Toxin-1

Etymology 1. Toxic

• Greek toxikon = poison

2. Shock

• From French choc = sudden impact/collapse
  👉 In medicine: circulatory collapse (low blood pressure)

3. Syndrome

• Greek:

  • “syn-” = together

  • “dromos” = running/course

👉 Syndrome = a group of symptoms occurring together

4. Toxin (TSST-1)

• TSST-1 = Toxic Shock Syndrome Toxin-1
  👉 The first identified toxin causing this syndrome

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Definition

TSST-1 is a superantigen exotoxin produced by Staphylococcus aureus that:

👉 Triggers massive, non-specific activation of T-cells
→ leads to a cytokine storm

Normal Antigen Presentation

• Antigen sits in MHC II groove

• TCR recognizes specific antigen

👉 Activates:

• ~1 in 10,000 T cells (very controlled)

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🔴 Superantigen Mechanism (TSST-1)

Produced by Staphylococcus aureus

👉 Instead of normal binding:

• Superantigen links MHC II directly to TCR

• Bypasses the antigen-binding groove

👉 Result:

• Activates:

  • 1 in 5 T cells (~20%)

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⚡ What happens next?

Massive activation → cytokine storm

Releases:

• IL-1 → fever

• TNF-α → hypotension (shock)

• IL-2 → T-cell proliferation

• “strepto-” → from Greek streptos = “twisted” or “chain-like”

• “-coccus” → from Greek kokkos = “berry” or “round”

👉 Streptococcus = “chains of round (spherical) bacteria”

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Definition

Streptococcus is a genus of Gram-positive, spherical (cocci) bacteria that:

• Grow in chains or pairs (diplococci)

• Are catalase-negative (key distinction from Staphylococcus)

• Are non-motile and non–spore forming

• Often live in the:

  • Respiratory tract

  • Gastrointestinal tract

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🔬 Key Characteristics (from your slide, explained)🟣 Gram-positive cocci

• Thick peptidoglycan → stain purple

Important Exception

• Streptococcus pneumoniae

• Viridans streptococci

👉 DO NOT have Lancefield antigens
→ Cannot be classified this way

S. pyogenes produces hemolysins = toxins that destroy red blood cells (RBCs) → causes β-hemolysis (clear zone on blood agar)

👉 Two main ones:

• Streptolysin O

• Streptolysin S

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🔴 1. Streptolysin O (SLO) 📖 Key Features

• O = Oxygen-labile (inactivated by oxygen ❌)

• Works only in anaerobic (low O₂) conditions

👉 That’s why:

• Hemolysis is better seen below the agar surface

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💥 What it does

• Forms pores in cell membranes

• Kills:

  • RBCs

  • WBCs

  • Platelets

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🧪 Clinical importance

• Highly antigenic → body makes antibodies

• These are measured as:

  • ASO (Anti-Streptolysin O) titer

👉 Used to diagnose:

• Rheumatic fever

• Post-strep infections

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🟡 2. Streptolysin S (SLS) 📖 Key Features

• S = Stable in oxygen ✅

• Works on surface of agar

👉 Responsible for:

• The visible β-hemolysis (clear zone) you see in lab

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💥 What it does

• Also destroys RBCs → contributes to hemolysis

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❗ Key difference

• NOT antigenic
  👉 No antibody formation → no diagnostic test

S. pyogenes produces exotoxins that:
👉 Spread beyond the throat/skin
👉 Cause systemic disease (rash, shock, tissue destruction)

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🔴 1. Erythrogenic toxin (Pyrogenic exotoxin) 📖 What it does

• Causes the rash of scarlet fever

🧠 Mechanism

• Acts as a superantigen → massive cytokine release

• Leads to:

  • Fever

  • Red “sandpaper” rash

  • Strawberry tongue

⚠ Key idea

• Bacteria stay in the pharynx

• But toxin spreads through bloodstream

👉 Disease = toxin-mediated, not direct invasion

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⚡ 2. Pyrogenic Exotoxin A (SpeA) 📖 What it does

• Causes Strep toxic shock–like syndrome

🧠 Mechanism

• Superantigen

• Activates huge numbers of T-cells → cytokine storm

💥 Results

• High fever

• Hypotension

• Multi-organ failure

👉 Very similar to S. aureus TSST-1

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💀 3. Exotoxin B (SpeB) 📖 What it is

• A protease enzyme

🧠 What it does

• Breaks down proteins in tissue

• Rapidly destroys:

  • Fascia

  • Muscle

⚠ Clinical effect

👉 Necrotizing fasciitis (“flesh-eating disease”)

• Extremely fast spreading

• Severe pain

• Tissue death (necrosis)

These are physical components on the bacteria (not toxins) that help it:

👉 Stick to cells
👉 Avoid the immune system
👉 Survive and spread

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🔴 1. M Protein (MOST IMPORTANT) 📌 What it does 🧲 Adherence

• Helps bacteria attach to throat (pharyngeal) epithelial cells

👉 First step in infection

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🛡 Blocks opsonization

• Prevents complement (C3b) from coating the bacteria

👉 Without opsonization:

• Immune cells can’t recognize it easily

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🚫 Antiphagocytic

• Stops neutrophils/macrophages from engulfing (phagocytosis)

Big Picture

These enzymes are called “spreading factors” because they help bacteria:

👉 Break through tissue barriers
👉 Escape immune traps
👉 Spread rapidly through the body

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🧪 1. DNases (Deoxyribonucleases) 📌 What they do

• Break down DNA

🧠 Why that matters

• Infection sites contain lots of dead cells + neutrophils

• These release DNA → thick pus

👉 DNase:

• Liquefies pus

• Helps bacteria move through infected tissue

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🧪 Clinical clue

• Body makes anti-DNase antibodies
  👉 Used to detect recent strep infection (like ASO)

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🧬 2. Hyaluronidase 📌 What it does

• Breaks down hyaluronic acid

🧠 Why that matters

• Hyaluronic acid = “glue” of connective tissue

👉 When broken:

• Tissue becomes loose

• Bacteria can spread between cells

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💡 Nickname

👉 “Spreading factor” (classic exam term)

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🩸 3. Streptokinase 📌 What it does

• Breaks down fibrin clots

🧠 Why that matters

• Body tries to trap bacteria in clots

👉 Streptokinase:

• Dissolves the clot

• Frees bacteria → spreads infection

Group A Strep causes 2 categories of disease:

🔥 1. Suppurative (pus-forming, ACTIVE infection)

👉 Bacteria are present and invading tissue

⚠ 2. Non-suppurative (post-infectious, IMMUNE-mediated)

👉 Bacteria are gone, but immune system causes damage

Streptococcus agalactiae etymology combines Greek and Latin roots meaning "chain-forming berry without milk." It derives from streptos (twisted/chain), kokkos (berry/sphere), and agalactiae (no milk), referencing its chain-like structure under a microscope and its historical identification as a cause of bovine mastitis that stops milk production

Big Picture

Group B Strep is:
👉 Normal flora in women
👉 But becomes dangerous when transmitted to newborns

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🌍 1. Normal Flora

• Found in vagina (5–35% of women)
  👉 Usually harmless in adults

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🔬 2. Hemolysis

• β-hemolytic (like Group A)

• But:

  • Less clear hemolysis

👉 Lab clue: weaker clearing on blood agar

. MOST IMPORTANT CLINICAL POINT

👉 Most common cause of:

• Neonatal sepsis

• Neonatal meningitis