Microbial Infectious Diseases of the Respiratory System: Strep Throat, Tuberculosis, and Influenza

Microbial Infectious Diseases of the Respiratory System

Overview of Respiratory System Microbiology

The respiratory system is a complex network of tissues and organs that is constantly exposed to airborne microorganisms. While most microbes present are not pathogenic, several can cause significant infectious diseases. This section covers the major microbial diseases affecting the respiratory tract: strep throat, tuberculosis, and influenza.

• High microbial diversity exists within and among respiratory tissues/organs.

• Most microbes are not pathogens.

• Approximately 33% of healthy people carry Staphylococcus aureus in the nose (can be opportunistic).

• Many organisms colonize the upper throat.

Chemical and Mechanical Defenses of the Respiratory System

The respiratory system employs several defense mechanisms to prevent infection:

• Lymphoid tissues (tonsils, adenoids) contain B and T lymphocytes for immune surveillance.

• Mucus contains antimicrobial substances: dermicidins, lactoferrin, lysozyme, and secretory IgA.

• Ciliated mucous membranes line the trachea, bronchi, and bronchioles, helping to trap and expel pathogens.

Streptococcal Respiratory Diseases (Strep Throat and Scarlet Fever)

Streptococcus pyogenes: Pathogen and Virulence Factors

Streptococcus pyogenes is the primary cause of strep throat, a common bacterial pharyngitis.

• Gram-positive, beta-hemolytic bacterium.

• Frequently infects the throat.

• Virulence factors include:

  • Capsule with M protein and hyaluronic acid – evades phagocytosis.

  • Streptolysins – lyse blood cells.

  • Streptokinases – lyse blood clots.

  • Pyrogenic toxins – stimulate leukocytes to release cytokines, causing fever, rash, and shock.

• Lancefield groupings based on teichoic acid antigens; Group A strep is caused by S. pyogenes.

Signs and Symptoms

• Redness at the back of the pharynx

• Swollen lymph nodes

• Purulent abscesses over tonsils

• Pain during swallowing

• Fever, malaise, headache

• Bacteria can spread to larynx and bronchi, causing laryngitis and bronchitis

Scarlet Fever (Scarlatina)

Scarlet fever can develop if S. pyogenes is infected with a lysogenic phage encoding pyrogenic toxins.

• Occurs after 1-2 days of pharyngitis

• Toxins trigger fever and a diffuse rash that begins on the chest and spreads

• Tongue becomes strawberry red

• Rash disappears after about one week; skin sloughs off

Epidemiology

• Spread via respiratory droplets

• Most common in winter and spring among children ages 5-15

• Humans are the only reservoir

Treatment and Prevention

• Antibiotics: Oral or intramuscular penicillin G, penicillin V, or amoxicillin

• Antibodies against M protein provide long-term protection

• More than 50 kinds of M proteins; antibiotic intervention often precludes development of protective antibodies

Tuberculosis

Pathogen and Virulence Factors

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), a chronic bacterial infection of the lungs.

• Gram-positive rod

• Mycolic acid in cell wall (acid-fast positive)

• Unique characteristics:

  • Very slow growth

  • Protected from destruction following phagocytosis

  • Intracellular growth

  • Resistant to Gram staining, detergents, many common antimicrobial drugs, and desiccation

• Virulent strains produce cord factor:

  • Prevents fusion of phagosomes with lysosomes, inhibiting phagocytosis

  • Cell wall glycolipid causes daughter cells to remain attached in parallel alignments

Pathogenesis: Granuloma Formation

• Macrophages in alveoli phagocytize organisms but cannot digest them

• Bacteria replicate within macrophages, gradually killing them

• T cells produce lymphokines that attract and activate more macrophages, triggering inflammation

• Collagen fibers enclose granuloma

• Immune system reaches stalemate with Mycobacterium

Secondary (Reactivated) Tuberculosis

• Occurs when bacteria break out of the granuloma

• Organisms rupture tubercle and reestablish active infection

• Called "consumption"

• Bacteria spread through lungs via bronchioles

• Occurs in about 10% of patients

Treatment and Prevention

• Some strains are multidrug resistant (MDR) or extremely drug resistant (XDR)

• Bedaquiline: antibiotic that targets ATP synthase in Mycobacterium

• BCG vaccine (live, attenuated):

  • Not recommended for adults; low efficacy

  • In the U.S., mass immunization not warranted due to low prevalence of TB

Influenza

Pathogens and Virulence Factors

Influenza is a viral respiratory disease caused by orthomyxoviruses, primarily types A and B.

• Structure:

  • Eight different ssRNA molecules as genome

  • Glycoprotein spike variation:

    • Neuraminidase – hydrolyzes mucus in lungs, allowing virus to spread

    • Hemagglutinin – binds to pulmonary epithelial cells and triggers endocytosis

• Infects lung epithelial cells in upper and lower respiratory tract

Antigenic Drift and Shift

• Antigenic drift: 1 virus enters the host and mutates, causing new strain with slight differences

• Antigenic shift: 2 viruses enter the host, genomes reassort, and a brand new virus hybrid exits the cell

Historical Example: 1918 H1N1 Pandemic (Spanish Flu)

• Reduced average life expectancy by 12+ years

• Killed 50 million people worldwide

• Novel virus arose through antigenic shift (mammal + avian virus reassortment)

• H1N1 has undergone antigenic drift since 1918 and has different protein features

Pathogenesis, Signs and Symptoms, and Treatment

Pathogenesis	Signs and Symptoms	Treatment
Droplet transmission Airborne transmission Indirect contact transmission Direct contact transmission	Sudden fever Pharyngitis Dry cough Malaise Headache	Antiviral drugs administered within 48 h of infection Two drugs available; both inhibit neuraminidase: Oseltamivir (Tamiflu) Zanamivir (Relenza)

Key Terms and Concepts

• Beta-hemolytic: Bacteria that completely lyse red blood cells on blood agar.

• Pharyngitis: Inflammation of the pharynx, often causing sore throat.

• Granuloma: A mass of immune cells formed to wall off persistent pathogens.

• Antigenic drift/shift: Mechanisms by which influenza viruses change their surface proteins, leading to new strains.

Formulas and Equations

• Antigenic shift (reassortment):

• $\text{New Virus Genome} = \text{Segment A}_{\text{virus 1}} + \text{Segment B}_{\text{virus 2}}$

• Antibiotic mechanism (Bedaquiline):

• $\text{Inhibition of ATP Synthase} \rightarrow \text{Prevention of Bacterial Energy Production}$

Additional info: These notes expand on the original slides by providing definitions, context, and examples for each disease, as well as a summary table for influenza pathogenesis, symptoms, and treatment.