Corynebacterium diphtheriae

Corynebacterium diphtheriae / Klebs-Loeffler's bacillus

• These are non-spore-forming, Gram-positive bacilli
• Possess a pleomorphic, club-shaped morphology
• Exhibit X, Y, V, or L configurations, resembling "Chinese letters/Cuneiforms" or "palisades"
• Metachromatic granules (volutin granules or Babe-Ernst granules) are present
• Non-motile and aerobic/facultative anaerobic
• Catalase-positive but oxidase-negative
• Found in the human nasopharynx and skin
• Transmitted through direct contact with respiratory secretions or skin exudates

Pathogenesis and Clinical Manifestations of Diphtheria

• Diphtheria is an acute disease caused by toxigenic strains of C. diphtheriae
• Incubation period ranges from 2-5 days, but can be 1-10 days

Respiratory Diphtheria (pharyngeal, tonsillar, laryngeal, nasal)

Symptoms

• Gradual onset of pharyngitis and sore throat with a low-grade fever
• Dyspnea signifies difficulty in breathing

Localized Manifestations

• Formation of a pseudomembrane, composed of fibrin, necrotic host cells, and bacteria
• Gray-white patches occur in pharynx, tonsils, uvula, and palate
• Extension can lead to suffocation, coma, and death
• "Bull neck" appearance occurs with marked edema and lymphadenopathy in severe cases

Systemic Manifestations

• Myocarditis, polyneuritis, nephritis, and thrombocytopenia may occur
• Polyneuritis can cause paralysis of eye muscles, limbs, and diaphragm after the 5th week
• Death occurs in 5-10% of cases
• Secondary pneumonia and respiratory failure can occur
• Myocarditis is the most common cause of mortality

Cutaneous diphtheria (wound diphtheria)

• Less common
• Can be associated with non-toxigenic strains
• Infected skin lesions occur
• A membrane can form on the infected wound
• Systemic complications are less frequent

Virulence Factors of Diphtheria

Diphtheria Exotoxin (Diphtherotoxin)

• Is a major virulent toxin produced by lysogenized strains infected by beta-prophages carrying the tox gene
• Absorbed into mucous membranes and blood circulation, causing local tissue destruction and damage to PNS, heart, and other organs

Fragment A

• Interacts metabolically with factors in the cytoplasm
• Active, enzymatic/catalytic
• Inactivates EF-2, inhibiting polypeptide chain elongation and protein synthesis
• Necrotizing and neurotoxic effects

Fragment B

• Binds to and facilitates the entry of the toxin into the cytoplasm
• Receptor-mediated endocytosis

Prevention and Control of Diphtheria

• Series of vaccinations with diphtheria toxoid (induces protective antitoxin antibodies)
  • DTaP (Diphtheria, Tetanus, acellular Pertussis) is for young children
    • Routine immunization program (free)
      • 3 primary (2, 4, 6 months) & 2 boosters (15-18 months and before school entry/4-6 years old) -If there’s an outbreak: early as 6 weeks (6, 10, 14 weeks)
  • Tdap has lower doses of diphtheria and acellular pertussis
    • It is for older children (4-12 years old), pregnant women (27-36 weeks), and adults
• Persons with suspected respiratory diphtheria should be promptly given diphtheria antitoxin (antibodies)
• Chemotherapy is implemented

Other Corynebacterium Species

C. jeikeium

• Isolated from acutely ill or immunocompromised patients
• Causes bacteremia with a high mortality rate and resistance to common antibiotics

C. pseudodiphtheriticum

• Is normal flora of the nasopharynx
• Causes respiratory tract infections
• Can colonize natural and artificial heart valves

C. xerosis

• Is normal flora of the eye, skin, and mucous membranes
• It is an opportunistic pathogen in eye and postoperative infections

C. minutissimum

• Is the causative agent of erythrasma
• Erythrasma is a superficial skin infection with small, brown-red macular areas
• Gives coral/brick red fluorescence when exposed to Wood’s light due to porphyrin

C. striatum

• Causes hospital-acquired respiratory tract and other infections

C. urealyticum

• Slow growing species multiply resistant to antibiotics
• causes acute/chronic encrusted urinary tract infections (alkaline urine pH and crystal formation)

C. amycolatum

• Isolated in clinical laboratories

Listeria monocytogenes

General Characteristics

• These are non-spore-forming, small, Gram-positive bacilli (coccobacilli)
• Display "Chinese letters/Cuneiforms" configuration
• Non-motile at 37°C but motile at 25°C (22-28°C)
• Nonencapsulated and facultative anaerobic
• Catalase-positive but oxidase-negative
• Capable of growing and surviving in a refrigerator (4°C, low pH, and high salt)

Habitat

• Widespread in the environment (soil, water, vegetation) and fecal flora of animals
• Transient constituents of human intestinal flora excreted in the feces (1-10% of healthy humans)

Transmission

• Food-borne transmission occurs through ingestion of contaminated milk, cheese, ice cream, raw vegetables, poultry, and meat
• Vertical transmission occurs prenatally or postnatally

Pathogenesis and Clinical Manifestations of Listeriosis

General Info

• Facultative intracellular pathogens that infect phagocytes and non-phagocytic cells
• Can spread to the CNS and pregnant uterus

Symptoms in Normal Adults

• Mild/subclinical infection
• Fever, diarrhea, and sore throat

Symptoms in Children and Immunocompromised Adults

• Meningitis and septicemia are common

Symptoms in Pregnant Women

• Typically experience a mild flu-like illness without meningitis
• Bacteremia may occur concomitantly

Result of Amnionitis

• Abortion, stillbirth, or delivery of an acutely ill infant

Diseases affecting Neonates

• Result of infection in utero
  • Early-onset syndrome (Granulomatosis infantiseptica
    • Results in neonatal sepsis, pustular lesions, and granulomas containing L. monocytogenes
    • Can be deadly
  • Late-onset syndrome (Caused by serotype 4b)
    • Meningitis (between birth and third week of life)

Virulence Factors of Listeria

Adhesin Proteins (Ami, Fbp A, and Flagellin)

• Facilitate bacterial binding/adhesion to host cells

Internalins (A and B)

• Cell wall surface proteins that interact with E-cadherin
• Promotes phagocytosis into the epithelial cells

Listeriolysin O

• Enzyme produced at low pH
• Lyses phagolysosome membrane
• Allows escape into the cytoplasm of the epithelial cell

Act A

• Surface protein that induces host cell actin polymerization
• Propels the listeria to the cell membrane of the epithelial cells
• Permits movement from cell to cell without being exposed to antibodies, complements, and phagocytes

Prevention and Control of Listeria

• Avoidance of unpasteurized dairy products
• Adequate pasteurization temperatures and thorough cooking foods
• No vaccine available
• Cold storage is not an effective control measure

Erysipelothrix rhusiopathiae

General Characteristics

• Gram-positive bacilli arranged singly, in short chains, or in long non-branching filaments
• Non-motile
• Forms small, transparent, glistening colonies that may be alpha-hemolytic or gamma-hemolytic on BAM
• Catalase-negative and oxidase-negative
• Exhibits "test tube brush-like" or "pipe cleaner" growth in gelatin stab culture

Habitat

• Found in land and sea animals worldwide (vertebrates and invertebrates)
• Causes disease in domestic swine (erysipelas), turkeys, ducks, and sheep

Transmission

• Direct inoculation from animals or animal products
• Affects fishermen, fish handlers, abattoir workers, and butchers

Clinical Manifestations

• Erysipeloid: nodular type of cellulitis
  • Usually occurs on the fingers by direct inoculation at the site of a cut or abrasion ("seal finger" and "whale finger")
• Diffuse cutaneous form and bacteremia with or without endocarditis (both rare)
• Septic arthritis

Prevention and Control

• Vaccinating pigs helps prevent transmission
• Wearing protective gloves recommended

Lactobacillus species

General Characteristics

• Gram-positive bacilli within square ends, arranged in pairs and in chains
• Anaerobes that can be aerotolerant
• Non-motile
• Catalase-negative
• Alpha-hemolytic
• Vancomycin resistant

Habitat

• Normal flora of the human vagina, GIT, and oropharynx

Facts

• Glycogen (vaginal epithelial cells) is metabolized by lactobacilli to lactic acid
• Lactic acid helps maintain the low pH (4-5) of normal adult female genital tract
  • this favors lactobacilli growth but inhibits most other organisms
• Rarely cause disease, but may be found occasionally in deep-seated infections