Bacterial Structures and Adhesion

GDC Learning Outcomes

• Learning outcomes include explaining general and systemic diseases and their relevance to oral health.
• Learning outcomes include explaining the aetiology and pathogenesis of oral disease.
• Learning outcomes include explaining the potential routes of transmission of infectious agents in dental practice.

Intended Learning Outcomes

• Define the terminology associated with virulence and virulence factors.
• List the pathogens that infect the human body.
• Describe the various mechanisms that pathogens deploy to destroy or cause malfunction of host cells, and evade the immune response.

Terminology

• A pathogen is any microorganism able to cause disease in a host organism.
• Primary pathogens are environmental microbes that can cause disease in otherwise healthy individuals.
• Opportunistic pathogens are members of the normal microbiota, causing disease only in immunocompromised hosts.
• Pathogenicity: the ability of a pathogen to cause disease

Pathogenic Diseases

• Pathogenic diseases exist for bacteria, virus, fungi, and protists

Terminology

• Virulence: The degree or intensity of pathogenicity.
• Virulence Factors: The means a pathogen uses to cause damage, invasion, and infectivity.

Chain of Infection

• The chain of infection components are agent, virulence, dose, exposure, and susceptibility

Molecular Koch's Postulates

• The suspected causative agent must be absent from all healthy organisms but present in all diseased organisms.
• The causative agent must be isolated from the diseased organism and grown in pure culture.
• The cultured agent must cause the same disease when inoculated into a healthy, susceptible organism.
• The same causative agent must then be reisolated from the inoculated, diseased organism.

Process of Infection

• Virulence factors enable a pathogen to outcompete host cells and resist their defenses.
• To survive, pathogens require a suitable environment, a source of nutrients, and protection from harmful elements.

Virulence Factor Mechanisms

• Adhesion
• Evasion of phagocytosis via antiphagocytic factors
• Immunoevasion
• Immunosuppression
• Toxigenicity via exotoxins and endotoxins
• Enzymatic action via exoenzymes

Staphylococcus Aureus

• Toxins such as TSST-1, enterotoxins, and alpha-hemolysin
• Invasins such as coagulase, staphylokinase, and leukocidin
• Adhesins for host protein attachment are virulence factors for Staphylococcus aureus

Pathogen Entry, Adhesion and Colonisation

• Exposure -> Adhesion -> Invasion -> Colonization -> Toxicity -> Tissue Damage & Disease

Adhesion

• Pili
• Fimbriae
• Capsules
• Bacterial cell walls

Using Pili to Adhere to Host Cells

• Class IV pili exhibit 'twitching' motility.
• They are located at the poles of bacilli.
• They enable a 'gliding' motion along solid host cell surfaces.
• They retract and extend, enabling movement.
• Bacteria can 'slingshot' over the cellular surface using pili.

Adhesins

• Cell walls of bacteria contain surface structures that mediate specific attachment to host cells.

Bacterial Adhesin Examples and Host Sites

• Streptococcus pyogenes causes strep throat, its adhesin is protein F, and it attaches to respiratory epithelial cells.
• Streptococcus mutans causes dental caries, its adhesin is adhesin P1, and it attaches to teeth.
• Neisseria gonorrhoeae causes gonorrhea, its adhesin is Type IV pili, and it attaches to urethral epithelial cells.
• Enterotoxigenic E. coli (ETEC) causes traveler's diarrhea, its adhesin is Type 1 fimbriae, and it attaches to intestinal epithelial cells.
• Vibrio cholerae causes cholera, its adhesin is N-methylphenylalanine pili, and it attaches to intestinal epithelial cells.

Capsules

• Some bacteria produce capsules, which aid in adhesion.
• Capsules help in immune evasion by preventing phagocytosis by cells of the immune system.
• Capsule composition prevents antibody adhesion.
• Capsule size deters phagocytosis.

Fimbraie and Cell Walls

• Mycolic acid (waxy substance) is produced in it's cell wall by Mycobacterium tuberculosis acting as a protective coat which deters killing mechanisms when phagocytosed

Pathogen Entry, Adhesion and Colonisation

• Exposure -> Adhesion -> Invasion -> Colonization -> Toxicity -> Tissue Damage & Disease

Exoenzymes

• Extracellular enzymes are secreted by cells that function outside of those cells.
• Enable invasion of host cells and deeper tissues.
• Specific to particular tissue structure
• Enable invasion/supports own growth/defends against immune system

Exoenzyme Class Examples

• Glycohydrolases, such as Hyaluronidase S from Staphylococcus aureus, degrade the hyaluronic acid that cements cells together.
• Nucleases, such as DNase produced by S. aureus, degrade DNA released by dying cells.
• Phospholipases, such as Phospholipases C, degrade the phospholipid bilayer of host cells.
• Proteases, such as Collagenase, degrade collagen in connective tissue.

Toxins

• Toxins are biological poisons produced by some pathogens.
• Toxins can invade and damage tissues
• Toxigenicity is the ability of a pathogen to produce toxins that cause damage to host cells.
  • Endotoxins are derived from gram-negative bacteria.
  • Exotoxins

Endotoxins

• Endotoxins are derived from gram-negative bacteria and stimulate a general systemic inflammatory response.
• Remain stable at high temperatures, and require heating to 121°C (250°F) for 45 minutes to inactivate.
• If endotoxin concentration is low: host's inflammatory response against infection is effective
• If endotoxin concentration is high in the blood: causes a severe drop in blood pressure, multi-organ failure and possibly death.

Exotoxins

• Exotoxins are potent protein molecules produced by a wide variety of pathogenic bacteria.
• Specific in their action and the cells they interact with Each exotoxin then targets specific receptors on specific cells-damages those cells through individual molecular mechanisms.
• Inactivated by heat (>41°C/106°F)
• Even low concentrations of exotoxin can be lethal
• Grouped in 3 categories: intracellular targeting, membrane disrupting, superantigens

Terminology to Describe Pathogens in Bloodstream

• Usually end in '-aemia'.
  • Presence of bacteria in the blood - Bacteraemia.
  • Pus-forming bacteria in the blood - Pyaemia.
• Presence of toxins in the blood - Toxaemia.
• Multiplying bacteria in the blood - Septicaemia.

Virulence Factors Promoting Infection

• Further protection against the immune system:
  • The exoenzyme coagulase triggers fibrinogen-to-fibrin cascade enabling bacteria to be coated by fibrin clots, which prevents phagocytosis by staphylococcus aureus
  • Kinases stimulate digestion of fibrin clots for pathogens to escape and spread from the clot, but need to do this conditionally.
  • Antigenic variation alters surface proteins to avoid recognition by the host's immune response.

Further Protection Against the Immune System

• Destruction of phagocytes with the production of leukocidins
• Destruction of T lymphocytes
• Intracellular position prevents immune defenses from reaching pathogens
• Avoid killing methods within the phagocyte

Viral Virulence

• Adhesins are mediated by adhesins that are part of viral capsid or membrane envelope; they interact with specific cell receptors (tropism).
• Spike protein hemagglutinin on influenza virus & glycoprotein g20 found on HIV.
  • Antigenic variation occurs in some enveloped viruses.
  • Antigenic drift is a result of point mutations causing minor changes in the spike proteins.
  • Antigenic shift: gene re-assortment results in major changes in spike proteins

Porphyromonas Gingivalis

• Fimbriae modify and stimulate immune responses such as cytokine secretion or cytokine inhibition in the periodontium.
• Gingipains produced by p.gingivalis break down structural proteins of the periodontium, such as collagen, elastin & fibronectin

Streptococcus Mutans

• Main virulence factors associated with cariogenicity are adhesion, acidogenicity, and acid tolerance; these factors combined can change the ecology of dental plaque.
• Number of S mutans increases and pH drops quickly due to the increase in cariogenic bacteria that occurs when fermenting available carbohydrates. Susceptibility to enamel demineralization increases due to bacterial proliferation and volume of acid being produced.

Herpes Simplex Virus

• Hides from the immune system in neurons and non-neuronal cells, persisting for many years.
• Emerges as a pathogenic form with low immune resistance.
• Presents clinically as herpes labialis (cold sore).

Candida Albicans

• The most common etiological factor of opportunistic human fungal infections
• Main virulence factors are:
• Exoenzymes: secreted aspartyl proteases, and adhesions.
• Pleomorphism: C. albicans responds/ adapts to changing environmental conditions.

Adhesins as Virulence Factors in Candida Albicans

• Adhesins are virulence factors in candida albicans

Conclusion

• Pathogens evolve strategies that influence virulence through virulence factors, in order to increase and avoid immune responses.
• The relationship between pathogen and host cells is dynamic.
• The increase of cytotoxic T cells in hosts enables pathogens to produce escape mutations.
• Pathogens evolve and emerge, with the most successful taking advantage of the host without causing death.