Untitled Quiz

Pathogenicity & Virulence

• Pathogenicity and virulence describe an organism's ability to cause disease.
• Pathogenicity refers to differences between microbial species.
• Virulence refers to differences between strains of the same species.
• In practice, they are often used interchangeably.

To Cause Disease

• An organism must:
  • Maintain a reservoir (e.g., humans, animals, environment) before and after infection.
  • Leave the reservoir and access a new host.
  • Colonize the new host's body.
  • Harm the body.

Influences

• Factors that influence the organism's ability to cause disease include its structures and metabolic products.
• Whether or not a person contracts a disease depends not only on the microorganism but also on the number of bacteria that enter the body and the quality of the individual's immune defenses.

Virulence Factors

• Bacterial virulence factors are divided into two categories:
  • Factors that promote bacterial colonization of the host.
  • Factors that damage the host.

Virulence Factors Promoting Colonization

• These factors enable bacteria to:
  • Contact host cells.
  • Adhere to host cells and resist physical removal.
  • Invade host cells.
  • Compete for iron and other nutrients.
  • Resist innate immune defenses (e.g., phagocytosis).
  • Evade adaptive immune defenses.

Ability to Contact Host Cells

• Motile bacteria that can swim chemotactically toward mucosal surfaces have a better chance to contact mucous membranes, attach, and colonize; mucosal surfaces (e.g., bladder, intestines) constantly flush bacteria away to prevent colonization.
• Spirochetes, due to their thinness, internal flagella, and motility, are more readily able to penetrate host mucous membranes, skin abrasions, etc., enter the body and disseminate to other body sites.

Ulcers: H. pylori

• Helicobacter pylori swims through the stomach's mucus layer and adheres to the epithelial cells.
• To protect itself from stomach acid, it produces an acid-inhibitory protein.
• The bacterium then releases toxins damaging the gastric mucosa.
• This leads to a massive inflammatory response with leukocytes killing bacteria, but also damaging the mucus membranes.
• Without the mucus layer, gastric acid causes stomach ulcers.

Streptococcus pyogenes

• Streptococcus pyogenes produces streptokinase to lyse fibrin clots, allowing the infection to spread.
• The bacterium also produces DNase that degrades cell-free DNA in pus and reduces its viscosity.
• Both enzymes facilitate spread to new tissues.

Ability to Adhere to Host Cells and Resist Physical Removal

• The body's innate defenses physically remove bacteria through shedding of surface epithelial cells, coughing, sneezing, vomiting, diarrhea, and bodily fluids (e.g., saliva, blood, mucus, urine).
• Bacteria may resist physical removal by producing pili, cell wall adhesins, and/or biofilm-producing capsules.

Signal Transduction

• Physical attachment of bacteria to host cells can signal the activation of virulence-related genes.
• This is known as signal transduction.

Pili and Bacterial Adherence

• Some bacteria alter the adhesive tips of their pili to adhere to and colonize different cell types with diverse receptors and evade antibodies.

Adhesins

• Adhesins are proteins in the cell walls of various bacteria.
• They bind to specific receptor molecules on host cells, enabling intimate attachment, colonization, and resistance to physical removal.
• Many bacteria utilize one or more adhesins for colonization.
• Bordetella pertussis produces multiple adhesins.

Capsules and Biofilms

• Many normal flora bacteria produce a capsular polysaccharide matrix or glycocalyx.
• This forms a biofilm on host tissues.
• Biofilms are layers of bacterial populations adhering to host cells.
• Embedded in a common capsular mass, they are found in situations like dental plaque and inner ear infections.

Ability to Invade Host Cells

• Some bacteria produce adhesin molecules called invasins.
• These activate the host cell's cytoskeletal machinery, enabling bacterial entry by phagocytosis.
• Bacteria entering the cytoplasm are protected from complement, antibodies, and other body defenses.

Examples

• Streptococcus pneumoniae produces phosphorylcholine, an invasin enabling entry to cells and resisting phagocytosis.
• Streptococcus pyogenes's F and M proteins aid invasion of epithelial cells and maintain persistent infections.

Ability to Compete for Iron and Other Nutrients

• Pathogenicity is related to the bacterium's ability to successfully compete with host tissue and normal flora for limited nutrients.
• The generation time of bacteria in the body is typically slower than in a lab culture due to limited nutrients.

Nutritional Competition

• To be pathogenic, a bacterium must multiply in host tissue.
• The rate of bacterial replication is correlated with the probability of infection establishment.
• Bacteria compete for nutrients: synthesis of specific transport systems or cell wall components aiding nutrient uptake.
• Bacteria compete for iron, where the host body also makes adjustments to deprive the microorganism of this essential nutrient.

Siderophores

• Bacteria synthesize iron chelators called siderophores.
• Many siderophores are excreted and re-enter the cell to bind iron.
• Others are found on the cell wall, binding and transporting the iron into the bacterium.
• The concentration of free iron is low due to host-produced iron chelators.

Other Ways of Acquiring Iron

• Some bacteria produce receptors for siderophores from other bacteria, taking iron from them.
• Some pathogenic bacteria bind human iron-binding proteins like transferrin, lactoferrin, ferritin, and hemin as the iron source.
• Bacteria can secrete exotoxins to kill host cells, accessing iron if concentrations are low.

Resist Innate Immune Defenses

• Overview of Phagocytosis: The microbe surface must attach to the phagocyte's cytoplasmic membrane for ingestion.
• Unenhanced attachment generally recognizes pathogen-associated molecular patterns in microbial cell walls, not found on human cells.
• These patterns are recognized via endocytic pattern-recognition receptors on phagocytes.

Enhanced Attachment

• Enhanced attachment occurs through antibody molecules (e.g., IgG) or complement proteins (e.g., C3b, C4b) called opsonins that promote attachment.
• This process, known as opsonization, is more specific and efficient than unenhanced attachment.

Phagocytosis Continued

• Following attachment, polymerization and depolymerization of actin filaments forms pseudopods to engulf the microbe into a phagosome.
• Lysosomes fuse with the phagosome, digesting and destroying the microbe.

Complement Pathways

• Bacteria can interfere with the body's complement pathways.
• There are three pathways: classical, alternative, and lectin.
• These pathways, though activated differently, all produce beneficial complement proteins.

Complement Proteins

• Complement proteins are a set of serum proteins.
• When activated, they participate in: inflammation, phagocyte chemotaxis, opsonization, and lysis of membranes.

Capsules

• Capsules enable organisms to resist phagocytic engulfment.
• Capsules of some bacteria interfere with the body's complement pathways.

Other ways to resist phagocytosis

• Coagulase induces fibrin clot formation, which helps to resist phagocytosis.
• Pathogenic Yersinia, using a type III secretion system, delivers proteins that depolymerize actin microfilaments, needed for phagocytic engulfment.

The Type III Secretion System

• The bacterium produces pore-forming proteins that create a pore spanning the bacterium's and outer membrane and the host cell's plasma membrane.
• The system allows the bacterium to directly deliver proteins into the host cell cytoplasm.

Bacteria Resisting Phagocytic Destruction

• Escape from the phagosome into the cytoplasm prior to phagosome/lysosome fusion.
• Preventing phagosome/lysosome fusion by inserting por proteins.
• Producing enzymes that kill the phagosome.

Evading Adaptive Immune Defenses

• A major defense against bacteria is antibody production, with antibody tips (Fab regions) having shapes complementary to the bacterial proteins and polysaccharides (epitopes).

Avoiding Antibodies

• Bacteria alter adhesive tips of pili or surface proteins to avoid antibodies.
• Antibodies may not be made against some capsules.
• Bacteria coat themselves with host proteins like fibronectin, lactoferrin, or transferrin to avoid antibody binding.

Virulence Factors Damaging the Host

• The ability to produce cell wall components (PAMPs) that cause host cells to produce inflammatory cytokines.
• The production of harmful exotoxins.
• The ability to induce autoimmune responses.

Autoimmunity and Exotoxins

• Autoimmunity occurs when the body's immune defenses mistakenly attack the body (trigger often bacteria).
• Exotoxins are protein toxins secreted by living bacteria or released upon lysis.
• Three types:
  • Superantigens (Type I toxins).
  • A-B toxins and other toxins interfering with host cell function (Type III toxins).
  • Exotoxins damaging host cell membranes (Type II toxins).