Symbiosis, Infectious Diseases and Antibiotics

Symbiosis, Infectious Diseases and Antibiotics

Symbiosis, Infectious Diseases and Antibiotics

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Symbiosis

  • Any microorganism that spends a portion of part of its life or all of its life with another organism of a different species is called a symbiont
  • Relationship is symbiosis
  • Normal flora
  • Mixture of organisms regularly present at any site in an animal
    • Bacteria
    • Fungi
    • Virus (including bacterial viruses; bacteriophages)
    • Protozoa
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Symbiosis/Parasitism

  • If the symbiont either harms or lives at the expense of another organism it is a parasitic organism
  • Relationship is parasitism
  • Ectoparasite: a parasite that lives on the surface of a host organism
  • Endoparasite: a parasite that lives inside the body of an organism
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Benefits of the Normal Flora

  • Synthesise and excrete vitamins
    • Enteric bacteria secrete vitamin K and vitamin B12
  • Prevent colonisation by pathogens
    • Competing for attachment sites or for essential nutrients
    • Oral cavity, intestine, skin and the vaginal epithelium
  • Antagonise other bacteria
    • Production of substances which inhibit or kill non-indigenous species
    • Intestinal bacteria
    • Fatty acids and peroxides to highly specific bacteriocins, inhibit or kill other bacteria
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Benefits of the Normal Flora

  • Stimulate the development of certain tissues
    • Caecum
    • Caecum of germ-free animals is enlarged, thin-walled and fluid filled
  • The normal flora stimulate the production of cross-reactive antibodies
  • Imbalance of the normal flora leads to diseases
    • Obesity
    • Infections
  • Probiotics are microorganisms that are believed to provide health benefits when consumed
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Normal Flora

Infectious Diseases

  • Infectious diseases, also known as transmissable diseases or communicable diseases, comprise clinically evident illness (i.e. characteristic medical signs and/or symptoms of disease) resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism.

 

  • In certain cases, infectious diseases may be asymptomatic for much or even all of their course in a given host.
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Determinant Factors

  • Disease is intially transported into the host
    • Direct (human to human): coughing, sneezing, contact
    • Indirect: food, water, soil, surfaces
  • Adhere to colonise or invade the host
  • Multiply or complete its life cycle on or in the host or the host's cells
  • Initially evade the host's defence mechanism
  • Possess the mechanical, chemical or molecular ability to damage the host
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Normal Flora, Opportunistic Pathogens and Disease

  • Some normal flora are able to cause disease at a time of immune compromise - opportunistic pathogens
    • S. aureus, E. coli and Proteus vulgaris, C. albicans
  • Bacteria not normal flora but represents pathogenic organisms that may be present in a large percentage of the population without causing disease
    • MRSA, Clostridium difficile
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Long Term Use of Antibiotics and Opportunists

  • Extended use of broad spectrum antibiotics (e.g. lindamycin, lincomycin, third generation cephalosporins, fluoroquinolones) may give rise to a severe gastroenteritis resulting from a toxin produced by C. difficile
  • The inflammation of the colon is pseudomembranous colitis and is generally caused by antibiotic assocated diarrhoea (AAD)
  • C.difficile normally are indigenous bacteria, able to proliferate when most of the normal intestinal flora are killed by the antibiotic
  • Non-pathogenic strain may acquire virulence gene, e.g. toxin which cause disease
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Virulence Factors

  • Virulence: the degree or intensity of pathogenicity of an organism
  • Virulence factor: a microbial product that contributes to virulence
  • Examples of virulence factors in E.coli:
    • Adhesin - colonisation factor (CFA1, CFA2)
    • Endotoxin - lipopolysaccharise (pyrogen)
    • Exotoxin - heat labile (LT) enteroxin, vero cytotoxin-producing E.coli (VTEC) e.g. E.coli O157
    • Invasin (uropathogenic E.coli)
    • Capsule
  • Antibiotic resistance is not a virulent factor
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Toxins

  • Toxin: substance produced by organism that damages the host
  • Exotoxin
    • Usually proteins released by bacteria as it grows and divides
      • neurotoxins
      • enterotoxins
      • cytotoxins
  • Endotoxin
    • Bound to bacterium and is released when the bacterium lyses
    • Gram-negative bacteria; lipopolysaccharide
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Exotoxins

  • Required in very small amounts to cause disease
  • Usually strong antigenic: produce antitoxin in host
  • Inherently unstable: artificial immunisation
  • Often composed of protein subunits (e.g. Shigella toxins)
  • Mediate their effects outside and inside cells
    • membrane-damaging
    • membrane acting (disrupting signal following attachment to receptors)
    • intracellular
  • Bacterial exotoxins are some of the most toxic substances known
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Mechanism of Action of Bacterial Exotoxins

Endotoxins

  • Toxic at high doses compared with exotoxins
  • Stable
  • Weakly immunogenic
  • Capable of producing systemic effects
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Pathogenicity Islands

  • Virulence genes are contained in specific regions of DNA
  • Inserted DNA sequences within chromosome (e.g. Shigella, Salmonella and Yersinia, E. coli)
  • Specialised for export of virulence factors directly into cells
  • Confer a variety of virulence traits (e.g. cell adherence, cell entry, toxins)
  • Many seem to have been acquired in a single step from foreign source
  • Provides sudden radical changes in bacteria-host interactions
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Microbial Diseases

  • Infection - symptoms
    • Outside body
    • Inside: microflora
    • Acute
    • Silent
  • Infection - severity
  • Infection - causative agents
    • Similar symptoms (viruses, bacteria)
  • Identification
    • Isolation, identification (media, antibody/antigen, DNA)
  • Treatment
    • Identification is key, severity, choice of treatment
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Antibiotic of Choice

  • Determinants
    • Selective toxicity, therapeutic dose, toxic dose
  • Spectrum of activity
    • Broad, narrow, bacterial type (genus and species), antibiotic susceptibility profile of isolate
  • Resistance
    • Propensity for bacterial isolate to develop resistance
  • Activity
    • Bacteriostatic vs. bactericidal
  • Route of administration
    • Oral, intravenous
  • Side effects
  • Cost of antibiotic and duration of treatment
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Therapeutic Index

  • Therapeutic index/therapeutic dosage level is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death in animal studies or toxitity in human studies
  • Therapeutic index = toxic dose/therapeutic dose
  • Therapeutic index = TD50/ED50
  • TD50: dose that provides a toxicity in 50% of the population
  • ED50: minimum effective dose for 50% of the population
  • Higher the index the more effective and less toxic than antibiotic
  • Especially careful when treating diseases caused by eukaryotes
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Classes of Antibiotics

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Bacterial Resistance to Antibiotics

  • Methicillin-resistant Staphylococcus aureus (MRSA)
  • Vancomycin-resistant enterococci (VRE)
  • PEnicillin-resistant enterococci
  • Vancomycin insensitive Staphylococcus aureus (VISA)
  • Multidrug resistant (MDR) Mycobacterium tuberculosis (XDR, TDR)
  • NDM1 (New Delhi metallo-beta-lactamase 1) enterobacteria
  • ESBL Escherichia coli (extended spectrum beta-lactamase)
  • Multidrug resistant Acinetonbacteria spp.
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Mechanisms of Bacterial Resistance to Antibiotics

  • Intrinsic resistance: natural property of microorganism
    • Impermeability barrier (change in permeability)
    • Efflux
    • Enzymatic inactivation
  • Acquired resistance: can be transferred between bacteria
    • Decreased uptake/permeability
    • Decreased accumulation (efflux)
    • Enzymatic inactivation
    • Duplication and overproduction of targets
    • Modification of target site
    • Bypass of a metabolic pathway/enzyme
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