MICROBIAL MECHANISMS OF PATHOGENICITY

MICROBIAL MECHANISMS OF PATHOGENICITY

Illnesses

• Types of Illnesses

  • Genetic, infectious, or environmental causes.

  • Medical professionals analyze signs and symptoms to determine causes of illnesses.

Signs and Symptoms

• Definitions

  • Disease: A condition where normal structure or function of the body is damaged or impaired.

  • Infection: Successful colonization of a host by a microorganism, leading to disease. Microorganisms causing disease are termed pathogens.

• Signs: Measurable and objective indicators of disease (e.g., fever, heart rate, breathing rate, blood pressure).

• Symptoms: Subjective experiences felt by patients (e.g., nausea, pain, loss of appetite/smell/taste).

Signs and Symptoms Continued

• Syndrome: A group of signs and symptoms characteristic of a particular disease (e.g., COVID symptoms: fever, cough, loss of taste/smell, body aches).

• Asymptomatic Diseases: Some diseases do not show symptoms, leading to silent spread (e.g., Typhoid Mary).

Disease Classifications

• Infectious Disease: Any disease caused directly by a pathogen.

  • Communicable: Capable of spreading from person to person.

  • Contagious: Easily spread from person to person.

• Iatrogenic Disease: Caused by medical procedures.

  • Examples: sound treatments, catheterization, surgical site infections.

• Nosocomial Disease: Acquired in a hospital setting.

• Zoonotic Disease: Transmitted from animals to humans.

• Noncommunicable Disease: Not transmitted from person to person.

Types of Noninfectious Diseases

• Classification Examples:

  • Inherited: Genetic diseases (e.g., Sickle cell anemia).

  • Congenital: Present at birth (e.g., Down syndrome).

  • Degenerative: Progressive loss of function (e.g., Parkinson’s disease).

  • Nutritional Deficiency: Impaired body function due to nutrient lack (e.g., scurvy).

  • Endocrine: Malfunction of hormone-releasing glands (e.g., hypothyroidism).

  • Neoplastic: Abnormal growth (e.g., cancer).

  • Idiopathic: No known cause (e.g., Idiopathic juxtafoveal retinal telangiectasia).

Stages of Development of Disease

1. Incubation Period: Time between initial exposure and first symptoms.

2. Prodromal Period: Early/mid symptoms; first indication of illness.

3. Period of Illness: All symptoms present; individual is definitely sick and needs treatment.

4. Period of Decline: Recovering; fewer symptoms; most susceptible to secondary infections.

5. Period of Convalescence: Individual recovers strength and returns to pre-diseased state.

Cycle of Microbial Disease

• Components:

  • Reservoir

  • Portal of exit

  • Agent

  • Person-to-person transmission

  • Susceptible host

  • Mode of transmission

  • Portal of entry

Duration of Infectious Disease

• Acute Disease: Develops quickly, short duration (e.g., common cold).

• Chronic Disease: Develops slowly; individuals do not fully recover.

• Latent Disease: Causative organism is present but not causing symptoms; may become active later (e.g., shingles).

Early Concepts of Disease

• Early explanations focused on superstition, myths, and religion.

• Greeks believed diseases were caused by imbalance in natural forces or humors.

  • Example: An excess of blood led to bloodletting practices.

Pioneers of Microbial Pathogenicity

• Louis Pasteur (1822-95):

  • French microbiologist known for vaccination principles, microbial fermentation, and pasteurization.

  • Developed Germ Theory: Disease caused by multiplication of germs in the body.

• Robert Koch (1843-1910):

  • German physician and pioneering microbiologist.

  • Developed Koch's Postulates: Principles linking specific microorganisms to specific diseases.

Koch’s Postulates

1. The same pathogen must be present in every case of the disease.

2. The pathogen must be isolated from the diseased host and grown in pure culture.

3. The cultured pathogen should cause the disease when inoculated into a healthy, susceptible laboratory animal.

4. The pathogen must be isolated from the inoculated animal and shown to be the same as the original organism.

Exceptions to Koch’s Postulates

• Some microbes cannot be grown on artificial media.

• Different organisms may cause the same symptoms.

• Some pathogens can cause multiple diseases based on infection location or presence of lysogenic viruses.

Pathogenicity and Virulence

• Pathogenicity: Ability of a pathogen to cause disease.

• Virulence: Degree of pathogenicity; influences disease severity.

  • Contributing factors for infectious disease: Disease = Number of organisms × Virulence × Resistance of host.

Mechanisms of Disease Causation

• Invasiveness: Ability of microbe to colonize the host; microbial metabolism and multiplication cause damage.

• Toxicity: Poisons produced by organisms; may act far from the organism's location or after the microbe's death.

Microbial Entry Points

• Portals of Entry:

  • Mucous membranes.

  • Skin punctures (parenteral route).

  • Most pathogens prefer specific entry portals.

Measurements of Pathogen Potency

• LD50: Lethal dose to kill 50% of infected hosts in a given time.

• MLD: Minimum lethal dose; depending on host and pathogen.

• ID50: Infectious dose to cause infection in 50% of susceptible hosts; measures virulence.

Numerical Data for Pathogens

• Bacillus anthracis:

  • Portal of Entry ID50:

  • Skin: 10–50 endospores

  • Inhalation: 10,000–20,000 endospores

  • Ingestion: 250,000–1,000,000 endospores

• ID-50 for Selected Foodborne Diseases:

  • Viruses:

    • Hepatitis A: 10-100

    • Norovirus: 1-10

  • Bacteria:

    • E. coli (enterohemorrhagic O157): 10-100

    • E. coli (enteropathogenic): 10,000,000-10,000,000,000

    • S. enterica serovar Typhimurium: ≥ 1

  • Protozoa:

    • Giardia lamblia: 1

    • Cryptosporidium parvum: 10-100

Types of Pathogens

• Frank Pathogens: Commonly cause disease unless the individual is immunized (e.g., diphtheria, polio, chickenpox).

• Opportunistic Pathogens: Cause disease in compromised hosts (e.g., chemotherapy, HIV patients).

• Non-pathogens: Organisms not known to cause disease, though some become opportunistic (e.g., Bacillus subtilis, Enterobacter aerogenes).

Normal Flora

• Definitions:

  • Normal Flora: Microorganisms that colonize the human body without causing disease; includes both resident and transient flora.

  • Transient Flora: Present temporarily, later disappear.

Benefits of Normal Flora

• Microbial Antagonism: Competes for sites and nutrients against pathogens.

• Immune Response Enhancement: Organisms may have antigens similar to those of pathogens.

• Vitamin Production: Intestinal microbes synthesize vitamins like Vitamin K.

• Beneficial Substance Synthesis: Some organisms produce substances that are advantageous to the host (e.g., acidity production in vaginal bacteria).

Harmful Effects of Normal Flora

• Opportunistic Infections: Common in immunocompromised individuals.

• Conjugation: Possible gene transfer between normal flora and pathogens.

Symbiosis

• Definition: Relationships between normal flora and host.

Types of Symbiosis

1. Commensalism: One organism benefits, the other is unaffected (e.g., many surface organisms).

2. Mutualism: Both organisms benefit (e.g., intestinal bacteria).

3. Parasitism: One organism benefits at the expense of the other (typical of pathogens).

Cycle of Infection

• Reservoir of Infection:

  • Human Reservoir: Includes symptomatic, asymptomatic, and carriers.

  • Animal Reservoirs: Zoonoses - diseases of animals transmittable to humans.

  • Non-living Reservoirs: Soil (e.g., Bacillus anthracis), water (e.g., Giardia lamblia).

Portal of Exit

• Exits:

  • Feces, urine, respiratory discharge (sneeze/cough), skin lesions, vomiting, genital discharge, and blood (insects).

Modes of Transmission

• Contact Transmission:

  • Direct Contact: Non-traumatic (e.g., handshake, kiss) and traumatic.

  • Indirect Contact: Via non-living objects (fomites like towels, doorknobs).

• Droplet Transmission: Sneezing, talking, laughing.

• Vehicle Transmission: Water, air, food.

• Vector Transmission: Organisms causing disease transmission (mechanical and biological transmission modes).

Adherence

• Process: Pathogens attach to host tissues via adhesion.

• Adhesins: Ligands binding to host cell receptors; includes glycocalyx and fimbriae.

• Biofilms: Communities of microbes sharing nutrients form around adherence sites.

Portal of Entry

• Any body opening including: mucous membranes (digestive, respiratory, reproductive), skin punctures (by insects), and injections.

Invasiveness

• Invasiveness is dependent upon virulence factors:

  • Bacterial Capsules: Prevent phagocytosis (e.g., Streptococcus pneumoniae).

  • Cell Wall Components: Prevent phagocytosis or interfere with antibodies (e.g., Mycobacterium tuberculosis).

  • Necrotizing Factors: Substances that kill body cells (e.g., enzymes).

Capsules

• Glycocalyx surrounding the cell wall serves to impair phagocytosis.

  • Examples: Streptococcus pneumoniae (pneumonia), Haemophilus influenzae (pneumonia and meningitis), Bacillus anthracis (anthrax), Yersinia pestis (plague).

Cell Wall Components

• M Protein: Resists phagocytosis (Streptococcus pyogenes).

• Opa Protein: Facilitates attachment to host cells (Neisseria gonorrhoeae).

• Waxy Lipid (Mycolic Acid): Resists digestion (Mycobacterium tuberculosis).

Enzymes

• Leucocidins: Destroy neutrophils, inhibit macrophages (produced by staphylococcus and streptococcus).

• Hemolysins: Cause lysis of erythrocytes, releasing hemoglobin (e.g., Streptococcus pyogenes, Staphylococcus, Clostridium perfringens).

• Coagulase: Causes blood clotting, protecting bacteria from host defenses (Staphylococcus aureus).

• Fibrinolysins: Dissolve blood clots (e.g., Streptococcus and Staphylococcus).

• Hyaluronidase: Breaks down hyaluronic acid, aiding spread through connective tissue (Streptococcus and Clostridium perfringens).

• Collagenase: Dissolves collagen in tissue (Clostridium perfringens).

Toxicity

• Definition: Toxins produced by microorganisms may act remote from their site or after the organism dies.

Production of Toxins

• Toxins: Poisonous substances that cause fever, cardiovascular issues, diarrhea, and shock.

• Toxigenicity: A microorganism's ability to produce toxins.

• Toxemia: Presence of toxins in the host's blood.

• Intoxications: Toxin presence without microbial growth.

Types of Toxins

1. Exotoxins: Primarily produced by gram-positive organisms; proteins secreted that damage host cells or disrupt metabolism.

   • Antitoxins: Antibodies against specific exotoxins.

   • Toxoids: Inactivated exotoxins used in vaccines.

2. Endotoxins: Primarily from gram-negative organisms; part of the cell wall (lipopolysaccharide). Released upon cell death; less potent than exotoxins but induce the same biological response.

Characteristics of Exotoxins

• Soluble in bodily fluids; very potent; highly specific; produced by living cells.

• Types include neurotoxins, cytotoxins, and enterotoxins.

Characteristics of Endotoxins

• Less toxic than exotoxins but can be fatal; induce similar effects regardless of source.

Biological Effects of Endotoxins

• Causes fever, diarrhea, shock, leucopenia, hyperglycemia, and blood platelet fragility.

Comparison of Bacterial Exotoxins and Endotoxins

Evasion of Defenses

• Mechanisms include bacterial capsules, fimbriae, mycolic acid, coagulase production, proteases protecting against phagocytosis, and antigenic variation.