Pathogens and Virulence Quiz

Pathogens and Virulence

A pathogen is an organism capable of causing disease.
Opportunistic organisms rarely cause disease in healthy individuals but can cause serious infections in immunocompromised patients.
Virulence is a quantitative measure of pathogenicity.
The 50% lethal dose (LD50) is the number of organisms needed to kill half the hosts, while the 50% infectious dose (ID50) is the number needed to cause infection in half the hosts.
Lower LD50 or ID50 values indicate higher virulence - fewer organisms are needed to cause disease.

Infectious Diseases

Infectious diseases occur when microorganisms overwhelm the host defenses.
The organism or its products must be present in sufficient amounts to induce symptoms.
Key determinants include the number of organisms and their virulence.
Innate and acquired immunity are the primary host defenses.
Asymptomatic infections are common and identified by detecting antibodies against the organism in the patient's serum.

Bacteria and Disease

Bacteria cause disease through three major mechanisms:
- Direct Invasion and Inflammation
- Toxin Production:
  - Exotoxins are polypeptides released by the bacteria.
  - Endotoxins are lipopolysaccharides, part of the cell wall of gram-negative bacteria.
- Immune-mediated mechanisms

Types of Bacterial Infections

Communicable infections spread from host to host, e.g., tuberculosis.
Contagious infections are highly communicable.
Epidemic infections occur much more frequently than usual.
Pandemic infections have a worldwide distribution.
Endemic infections are constantly present at a low level in a specific population.
Inapparent or subclinical infections do not result in overt symptoms.
Some infections lead to a latent state, followed by reactivation of the organism and recurrence of symptoms.
Chronic carrier state involves continuous organism growth with or without symptom production.
Normal flora are permanent residents of the body and vary according to anatomical site.
Colonization refers to the presence of a new organism that is neither part of the normal flora nor the cause of symptoms.

Stages of Bacterial Pathogenesis

Transmission from an external source into the portal of entry.
Evasion of primary host defenses, such as skin or stomach acid.
Adherence to mucous membranes.
Colonization by bacterial growth at the site of adherence.
Disease symptoms caused by toxin production or invasion and inflammation.
Host responses: nonspecific and specific immunity.
Progression or resolution of the infection.

Transmission

Human-to-human or non-human sources (soil, water, animals) or fomite (e.g., towels).
Routes: respiratory tract, gastrointestinal tract, genital tract, blood transfusion, skin.
Vertical Transmission: through the placenta, during birth or breast milk.
Horizontal Transmission: person-to-person transmission.
Animals can be a reservoir or vector.

Adherence to Cell Surfaces

Pili, capsule, and glycocalyces facilitate adherence.
Pili promote adherence to the surface of human cells, enhancing the ability to cause disease.
E.coli and Neisseria gonorrhoeae have pili.
Glycocalyx in Staphylococcus epidermidis and Streptococcus viridans enables strong adherence to the endothelium of heart valves.
Biofilms formed by bacteria after attachment provide protection, especially on prosthetic valves and IV catheters.
Biofilms protect bacteria from antibiotics, antibodies, and neutrophils.
Important in the persistence of Pseudomonas in the lungs of cystic fibrosis and the formation of dental plaque and caries.
Foreign bodies are prone to infections; bacteria adhere to these surfaces, but phagocytes adhere poorly due to the absence of selectins and other binding proteins on artificial surfaces.

Invasion and Inflammation

Several enzymes play a role in pathogenesis:
- Collagenase and Hyaluronidase degrade collagen and hyaluronic acid, allowing bacteria to spread through subcutaneous tissue (important in cellulitis).
- Coagulase accelerates fibrin clot formation from fibrinogen, protecting bacteria from phagocytosis (Staphylococcus aureus).
- IgA protease degrades IgA, allowing the organism to adhere to mucous membranes (Neisseria gonorrhoeae, Haemophilus influenzae, and Streptococcus pneumoniae).
- Leukocidin destroys neutrophils and macrophages.
Virulence Factors:
- The capsule prevents phagocyte adherence to bacteria; anti-capsular antibodies enable more effective phagocytosis (opsonization).
- Cell wall proteins in gram-positive cocci, like the M protein of Streptococcus pyogenes, are antiphagocytic.
- Protein A of Staphylococcus aureus binds to IgG and prevents complement activation.
- Pili of Escherichia coli.
Types of Inflammation:
- Acute pyogenic infection: neutrophils predominate (e.g., Pneumonia).
- Chronic granulomatous infections: macrophages and T-cells predominate (e.g., Tuberculosis infection).
Intracellular Survival:
- Certain bacteria enhance their ability to cause disease by surviving intracellularly.
- Commonly cause granulomatous lesions.
- Obligate intracellular parasites: Chlamydia and Rickettsia.
- Facultative parasites: Mycobacterium, Legionella, Brucella, and Listeria.
Mechanisms for Intracellular Survival:
- Inhibition of phagosome fusion with the lysosome.
- Inhibition of phagosome acidification, reducing lysosomal degradative enzyme activity.
- Escape from the phagosome into the cytoplasm, avoiding degradative enzymes.

Bacterial Invasion

Bacterial invasion of cells involves interactions between specific bacterial surface proteins called invasins and cellular receptors.
Actin microfilaments are responsible for bacterial movement into the cell.
Bacteria typically reside in vacuoles known as phagosomes once inside the cell.
Some remain in phagosomes, others migrate into the cytoplasm, and some travel to adjacent cells through actin-formed tunnels.
Pathogenicity islands on the bacterial chromosome are clusters of genes encoding virulence factors.
These islands contain genes for adhesins, invasins, and exotoxins.
Nonpathogenic variants lack these islands.
After colonization and multiplication at the portal of entry, bacteria may invade the bloodstream and spread to other parts of the body.
The distribution to specific organs is largely determined by the presence of receptors for the bacteria on the surface of cells.

Toxin Production

Exotoxins:
- Secreted by both gram-positive and gram-negative bacteria.
- Polypeptides produced by genes located on plasmids or bacteriophages (e.g., diphtheria and cholera).
- Among the most toxic substances known.
Toxoids:
- Toxins treated with formaldehyde or heat.
- Lose their pathogenicity but retain immunogenicity.
- Used in vaccinations.
- Possess A (active) and B (binding) subunits.
Endotoxins:
- Integral part of the cell wall of gram-negative bacteria.
- Lipopolysaccharides (LPS) encoded on the bacterial gene.
- Cause fever, hypotension, and shock.
- Weakly antigenic with high mortality rates (30-50%).

Immunopathogenesis

In rheumatic fever and acute glomerulonephritis, disease symptoms result from the immune response to the presence of the organism.
In rheumatic fever, antibodies against the M protein of Streptococcus pyogenes cross-react with joint, heart, and brain tissue.
Inflammation occurs, leading to arthritis, carditis, and chorea, characteristic findings in this disease.

Different Strains, Different Diseases

Bacteria within the same genus and species can cause widely divergent diseases.
Different virulence factors are encoded on plasmids, transposons, phage genomes, and pathogenicity islands.
These transferable, extrachromosomal genetic elements account for the ability to cause various diseases.

Virulence Factors

Virulence factors are key components that promote bacterial survival, growth, and pathogenicity.
These factors enable the bacterium to:
- Adhere to host cells.
- Resist host defenses, such as complement and phagocytosis.
- Invade host tissues and spread.
- Produce toxins.

Typical Stages of Infectious Diseases

Incubation period: time between acquisition of the organism and the onset of symptoms.
Prodromal period: nonspecific symptoms occur.
Specific-illness period: characteristic symptoms of the disease.
Recovery period: the patient may become a chronic carrier or enter a latent phase.