Bacterial Pathogenicity and Virulence

• Pathogenic microorganisms cause infection or disease.
• Most microorganisms are generally harmless.
• Infection can be stopped if the host's defense mechanisms are successful.
• Some pathogens cause disease under certain conditions, like introduction to a normally sterile body site or infection of an immunocompromised host.
• In order to cause disease, a pathogen needs an infective dose, access to the host, adhere to host tissues, penetrate/evade host defenses, and damage the host either directly or through accumulation of microbial wastes.

Microbial Mechanism of Pathogenicity

• Portals of entry include mucous membranes, the respiratory, gastrointestinal, and genitourinary tracts, conjunctiva, skin, and the parenteral route.
• Penetration or evasion of host defenses can involve capsules, cell wall components, enzymes, antigenic variation, invasins, and intracellular growth.
• Damage to host cells occurs through siderophores, direct damage, toxins (exotoxins and endotoxins), lysogenic conversion, and cytopathic effects.
• Portals of exit are generally the same as the portals of entry for a given microbe.

Portals of Entry

• Mucous membranes (moist mucosa) are a common route for pathogens.
  • Entry is through the respiratory tract (most common), gastrointestinal tract, urinary/genital tracts, or conjunctiva.
• Skin (keratinized cutaneous membrane):
  • Some pathogens can infect hair follicles and sweat glands while few colonize the surface.
  • The skin is an impermeable barrier to microbes unless broken.
• Parenteral Route:
  • Pathogens penetrate the skin through punctures, injections, bites, cuts, or surgery.
  • Organisms are deposited directly into deeper tissues.
  • Most microbes need their preferred portal of entry to cause disease.
  • However, some microbes can cause disease from many routes of entry.
  • Microbes usually exit the host from the same original portal to spread disease.

Numbers of Invading Microbes

• Virulence and pathogenicity are often used interchangeably.
• Virulence is quantified by the number of organisms needed to cause disease in 50% of those exposed (ID50) or to kill 50% of test animals.
• The number of organisms required to cause disease varies greatly among pathogenic bacteria.
• The infectious dose of a bacterium depends primarily on its virulence factors.

Adherence

• Adherence is the attachment of microbes to the host at the portal of entry.
• Some bacteria use pili, like E. coli, to adhere to host cells while Group A Streptococci use similar structures called fimbriae.
• Other bacteria have cell surface adhesion molecules (adhesins).
• Adherence enhances virulence by preventing bacteria from being carried away by mucus or washed from organs as well as the urinary and GI tracts.

Adhesins and Receptors

• Pathogens have surface molecules called adhesins or ligands that bind to the host surface receptors.
• Microbial adhesins are typically glycoproteins or lipoproteins on the glycocalyx, capsule, capsid, pili, fimbriae, or flagella.
• Host receptors are proteins (for viruses) or carbohydrates (for bacteria) in the wall/membrane of the host cell
• The adhesion process can trigger biofilm formation.

Penetration/Evasion of Host Defenses

• The immune system has evolved to control many pathogens.
• It's important to note that pathogens have also developed ways to evade the immune response.

Evasion of Immune Response

• Capsules:
  • Composed of a glycocalyx layer outside the cell wall.
  • Impairs phagocytosis by preventing engulfment and destruction by Phagocytes, as it is a main virulence factor composed of glycocalyx layer (carbohydrates) outside cell wall.
• Cell Wall Components:
  • M protein of Streptococcus pyogenes: heat and acid resistant, mediates attachment to the bacterium of epithelial cells, and resists phagocytosis.
  • Fimbriae Opa (membrane protein): used by Neisseria gonorrhoeae to promote attachment and uptake by host epithelial cells and leukocytes, where Neisseria then grows.
  • Mycolic acid (waxy) of Mycobacterium tuberculosis resists digestion by phagocytes; Mycobacterium then grows inside phagocytes.
• Enzymes (Exoenzymes)
  • Includes Coagulases, Kinases, Hyaluronidase, Collagenase, or IgA proteases.
• Antigenic Variation:
  • Pathogens alter their surface antigens to escape recognition by antibodies and immune cells, with examples including Neisseria gonorrhoeae and flu viruses.
• Penetration into Host Cytoskeleton

Damage to Host Cells

• Using Host Nutrients:
  • Required for all cells, like iron, for both host and pathogen.
• Direct Damage to Colonized Area:
  • Growth and replication inside host cells results in host cell lysis.
  • Penetration through host cells causes damage.
• Production of Toxins:
  • Toxins are poisonous substances produced by exotoxins or endotoxins.

Plasmid and Pathogenicity

• Plasmids sometimes transfer genes that encode resistance to antibiotics or virulence factors, turning harmless bacteria into pathogenic bacteria, as seen with hemorrhagic E. coli.

Viral Pathogenesis

• Viruses can replicate only inside living cells (Obligate Intracellular).
• Pathogenic manifestations of viral infection are seen at the cellular level
• Virus initial infection may be mild or asymptomatic
• After the initial infection, the virus is often cleared completely by the immune system.
• In some cases, viruses can cause a persistent or latent infection following the first infection

Viral Pathogenesis at the Cellular Level

• Cells respond to viral infection with a variety of responses depending on the cell type and virus.
• Many viral infections cause no apparent morphologic or functional changes. When changes do occur, however, several responses can be recognized:
  • Cell death
  • Transformation
  • Cell fusion
  • Cytopathic effects

Initial Viral Infections

• Infection can either remain localized or disseminate into other organs
• Infections can be asymptomatic
• Typical symptoms in two forms:
  • Early symptoms at the primary site of infection
  • Delayed symptoms after dissemination from the primary site.
• Virus transmission can happen before symptoms which makes it difficult to control the spread.

Lysis & Lysogeny

• Bacteriophage:
  • Viruses that infect bacteria (Virulent vs. temperate)
• Lytic (Lysis) pathway:
  • Results in more viruses, leading to the lysis of the host cell.
• Lysogenic (Lysogeny) pathway:
  • The viral genome(prophage) is incorporated into the host and replicates along with cellular division.

Explore bacterial pathogenicity, virulence factors, and the infectious process. This includes adherence mechanisms, the role of adhesins, glycocalyx, and portals of entry. Also covered are factors affecting the establishment of infection and the significance of the infectious dose.