Pathogenicity and Infection 1

• Pathogenicity

  Ability of a pathogen to cause disease in a host
• Pathogenicity and Infection

  • Non-specific host defenses
  • Entry of the pathogen into the host
  • Colonization and growth
  • Virulence
  • Toxins
• Virulence factors

  Properties of the pathogen that allow it to successfully invade and cause disease in a host
• Normal microbiota

  • Acts as a defense against pathogens
• Antibiotic use

  Destabilizes commensal flora by killing susceptible strains, allowing antibiotic-resistant enterococcal strains to colonize new niches
• Anatomical defenses

  • Respiratory tree has epithelial lining with cilia to entrap and propel particles upward
• Susceptibility to infectious disease

  Infants and elderly more susceptible due to undeveloped/declining immune system and normal flora
• Factors increasing susceptibility

  Fatigue, exertion, poor diet, dehydration, drastic climatic changes, hormone imbalance
• Tissue tropism

  • Pathogens usually only infect specific tissues and cell types, with some exceptions
• Attachment to host

  Microbes gain a stable foothold at the portal of entry through binding between specific molecules on host and pathogen
• Attachment structures

  • Fimbrae
  • Flagella
  • Glycocalyx
  • Cilia
  • Spikes
  • Suckers
  • Hooks
  • Barbs
• Bacterial adherence

  Mediated by pili, fimbriae, and flagella binding to host cell surface glycoproteins
• Infectious dose

  Minimum number of microbes required for infection to proceed
• Virulence factor

  Any characteristic of a pathogen that enables it to establish itself and cause disease, often extracellular enzymes
• Urease production in Helicobacter pylori allows it to penetrate the stomach lining
• Surviving host defenses

  Initial response comes from phagocytes, which pathogens have various mechanisms to avoid
• Exotoxin

  Toxin secreted into tissue
• Exotoxins

  • Diphtheria toxin
  • Tetanus and botulism toxins
• Diphtheria toxin

  • Extremely potent (one molecule will kill a cell)
  • Disrupts protein synthesis
  • Caused by lysogenic bacteriophage (virus) found in Corynebacterium diphtheriae
• Tetanus and botulism toxins

  • Causal organisms (Clostridium tetani and C. botulinum) don't generally grow very much in infected tissues but instead release potent neurotoxins
• Action of Tetanus Neurotoxin

  Tetanus causes irreversible muscle contraction ('spastic paralysis' or Lockjaw)
• Action of Botulinum Neurotoxin

  Botulinum toxin, the most poisonous substance known, causes irreversible muscle relaxation ('flaccid paralysis')
• Endotoxin

  • Toxin released only upon cell death and lysis
  • These are lipopolysaccharides and thus are found only in Gram-negative organisms
• Endotoxins

  • Salmonella
  • E. coli
  • Shigella
• Types of exotoxins

  • Superantigens – excessive activation of immune system, e.g. Toxic Shock Syndrome
  • Membrane-disrupting toxins, e.g. streptolysin (S. pyogenes)
  • Intracellular-targeting toxins (a.k.a.) "A-B toxins", e.g. cholera toxin
• Enterotoxin

  Exotoxin that acts specifically on the small intestine
• Acute infection

  Comes on rapidly, with severe but short-lived effects
• Chronic infections

  Progress and persist over a long period of time
• Reservoir

  Primary habitat of pathogen in the natural world
• Source

  Individual or object from which an infection is actually acquired
• Biological vectors

  • Actively participate in a pathogen's life cycle
• Mechanical vector

  • Not necessary to the life cycle of an infectious agent and merely transports it without being infected
• Zoonosis

  Infection indigenous to animals but naturally transmissible to humans
• With zoonoses, humans don't (initially) transmit the disease to others
• At least 150 zoonoses exist worldwide; make up 70% of all new emerging diseases worldwide
• Impossible to eradicate the disease without eradicating the animal reservoir
• Zoonosis

  • Plague: Yersinia pestis
• Nosocomial Infections

  Diseases that are acquired or developed during a hospital stay
• 2 to 4 million cases/year in U.S. with approximately 90,000 deaths
• Nosocomial pathogens

  • Enterobacter spp.
  • Enterococci
  • Pseudomonas aeruginosa
  • Staphylococcus aureus
  • Coagulase-negative staphylococci
  • E. coli
  • Acinetobacter spp.
  • Klebsiella pneumoniae
  • Candida spp.