How microorganisms cause disease

• Microorganisms have evolved to survive and reproduce - causing disease in the host is a byproduct of this process. The disease pathology may offer a survival advantage to the pathogen, but not in every case.
• Factors affecting the outcome of microorganisms

  • features of microorganism - virulence factor
  • features of host e.g. nutritional status, immunosuppression
  • competition with other microorganisms
  • actions of doctors e.g. antibiotics, immunosuppressive drugs, surgery
• Diarrhoea is a common side effect of antibiotic treatment, occurring in 2-25% of people taking antibiotics. The most common common cause of antibiotic-associated diarrhoea is disruption of the usual gut flora; around 20-30% of cases are caused by Clostridium difficile infection.
• Infection - invasion and multiplication of microbes in the hosts tissues that lead to cellular injury as a result of: their multiplication, production of toxins, immune response or competition in metabolism.
• Colonisation - microbes living in host without causing injury
• Protist - a eukaryote that is not an animal, plant, fungi. Examples include Plasmodium and Trypanosoma, Giardia, Entamoeba
• Protozoa - a protist that is not photosynthetic
• Local - confined to a small area of the body near the site of entry. e.g. hair follicle infected by staphylococcus or a pneumonia confined to the lungs
• Focal - a pathogen spreads to a secondary location e.g. gum infected by streptococcus that gains access to the bloodstream and causes secondary infection elsewhere.
• Systemic - a pathogen is disseminated throughout the body e.g. varicella-zoster virus enters through the respiratory system and spreads throughout the body resulting in a rash
• Pathogen - a microorganism that can cause disease
• Pathogenicity - the ability of an organism to cause disease
• Virulence - the degree of disease caused by an organism
• Virulence factors - the molecules produced by the organism that add to their effectiveness in replicating within the host
• ID50 is the number of microorganisms required to cause active infection in 50% of inoculated animals
• Which types of bacteria would not survive outside of the human host?

  Sexually transmitted bacteria
• Spore forming organisms of clinical significance – Clostridium and Bacillus. For each of these organisms it is the toxins that cause the disease but their survival is part of their pathogenic process.
• Clostridium difficile

  • very important hospital acquired infection
  • spores are resistant to alcohol hand gel
  • therefore need to be physically removed with soap and water
  • hydrogen peroxide fogging
• Biofilms

  • community of bacteria attached to surfaces embedded in extracellular polymeric substances
  • pseudomonas aeruginosa can form biofilms in tap assemblies - compromises hand washing procedures
  • protects against desiccation and chemical attack e.g. chlorine
  • some patient groups particularly susceptible to P.aeruginosa infections
• Microorganisms frequently gain access to mucosal surfaces - respiratory and gastrointestinal tract
• The respiratory and gastrointestinal tracts are particularly vulnerable portals of entry because particles that include microorganisms are constantly inhaled or ingested, respectively.
• In the gut, microorganisms move towards food source or to reach mucosal surface.
• Rod shaped bacteria e.g. salmonella, E. coli, campylobacter, have flagella - filamentous protein structures with a motor in the plasma surface. The protists Entamoeba and Giardia also move but in different ways.
• If campylobacter mutate so that they have no motility or the flagella are truncated there is a 200 fold reduction in ability to invade cells.
• The skin is a dry environment so flagella are ineffective. Microorganisms without flagella usually flow with the fluid surrounding them and adherence becomes more important.
• Adhesin is a protein or a glycoprotein that attaches to host cell receptors, expressed alone or associated with fimbrae/pilli, flagella, cilia.
• Adhesin conveys host cell and tissue specificity

  • Enterotoxigenic Escherichia coli which cause diarrhoea that express type 1 fimbrae which adhere to intestinal epithelial cells
  • uropathic Escherichia coli express P fimbrae which adhere to urethral and kidney mucosa
• Exotoxins are proteins coded for by the bacteria, released when the microbe is alive. Often target specific receptors - selectively target cells.
• Endotoxins are integral parts of the bacterial cell wall, released only if the microbe is destroyed.
• Clostridium botulinum toxin inhibits release of acetylcholine from neurones causing flaccid paralysis. This has the potential to stop breathing and cause death. Because of its action, low concentrations of botox are used for cosmetic and medical procedures, including the removal of wrinkles and treatment of overactive bladder.
• Cholera is endemic in parts of southern Asia, parts of Africa and Latin America. Associated with seasonal outbursts. Bacterium lives in estuarine conditions, and associated with shellfish.
• Cholera is characterised by severe watery diarrhoea, 30-40 litres per day. Treated by hydration
• Cholera exotoxin

  • activation of adenylate cyclase in intestinal cells
  • increased levels of cAMP and secretion of fluids and electrolytes out of the cell, causing diarrhoea
  • opens chlorine ion channels
  • inhibits sodium uptake
  • cholera toxin phage which carries cholera toxin gene and other virulence factors
• Toxic shock - streptococcus pyogenes or staphylococcus aureus
• Toxic shock syndrome - associated with incorrectly used tampons and blocking nasal passage to stop nose bleed. Involves the production of superantigens; stimulate T cells non-specifically without normal antigenic recognition. Cross link class II MHC on antigen presenting cell and T cell receptor.
• Clostridium tetani - inhibits release of inhibitory neurotransmitters in the central nervous system, causing spastic paralysis
• Corynebacterium diptheriae - inhibition of protein synthesis, causing cell death
• Streptococcus pneumoniae - proteins that assemble into pores in cell membranes, disrupting their function and killing the cell.
• Staphylococcus aureus - phospholipases that degrade cell membrane phospholipids, disrupting membrane function and killing the cell.
• Streptococcus pyogenes - stimulates excessive activation of immune system cells and release of cytokines from immune system cells. Life-threatening fever, inflammation and shock are the results.