Microorganisms Bacteria: unicellular prokaryotic organisms;
extremely diverse, adapted to essentially all habitats Fungi:
unicellular or multicellular eukaryotic organisms Protozoa:
unicellular eukaryotic organisms Algae: unicellular or
multicellular eukaryotic organisms
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Viruses Protein coat = capsid + nucleic acid DNA (ds or ss) or
RNA (ss) Not living organisms Not a true cell No cell membrane
Enveloped viruses have a stolen membrane that they acquire when
budding out of an infected cell No nucleus
Cell Wall Gram-positive Thick layer of peptidoglycan Teichoic
acids
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Cell Wall Gram-negative Thin layer of peptidoglycan Outer
membrane - additional membrane barrier Lipopolysaccharide (LPS) O
antigen Core polysaccharide Lipid A
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Cytoplasmic membrane Defines the boundary of the cell Transport
proteins function as selective gates (selectively permeable)
Control entrance/expulsion of antimicrobial drugs Receptors provide
a sensor system Semi-permeable; excludes all but water, gases, and
some small hydrophobic molecules Phospholipid bilayer, embedded
with proteins Fluid mosaic model
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Electron transport chain - Series of proteins that eject
protons from the cell, creating an electrochemical gradient Proton
motive force is used to fuel: Synthesis of ATP (the cells energy
currency) Rotation of flagella (motility) One form of active
transport across the membrane Cytoplasmic membrane Electron
transport chain
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Internal structures: Ribosomes
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Unique molecules in bacteria can be used as targets for
chemotherapy Cell wall: peptidoglycan, techoic acid Ribosomes
Unique biosynthetic pathways
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Bacterial growth & metabolism Binary fission Growth =
increase in # Generation time: time it takes to double the
population Pathogens with a short generation time cause rapidly
progressive disease (i.e. Vibrio cholera) Pathogens with a long
generation time cause chronic, slowly progressive disease (i.e.
Mycobacterium tuberculosis)
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Growth = increase in # Many of our drugs are most effective
against growing bacteria Interrupt cell wall synthesis
Interrupt/block replication Interrupt/block translation Interfere
with biosynthetic pathways
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Primary and Secondary metabolites
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Requirements for bacterial growth Environmental factors that
influence Temperature, pH, osmotic pressure, oxygen Nutritional
factors Carbon, nitrogen, sulfur, and phosphorous Trace elements:
iron
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Chemical control: choosing the right germicidal chemical What
is your goal? What type or organism are you targeting? What
environment are you treating? sterility vs. disinfection; level of
disinfection required dictates potency of chemical required
Toxicity: risk-benefit analysis Activity in presence of organic
material: most are diminished or inactivated Sensitivity of the
material to be treated Residue: toxic or corrosive vs residual
desired antimicrobial effect Cost and availability Storage and
stability: concentrate vs stock solution Environmental risk:
antimicrobials in the environment
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Innate immune system 1 st line defenses: skin, mucosal
barriers, secretions - antimicrobials (lysozyme), iron- binding
proteins (transferrin) Complement system Granulocytes (neutrophils,
eosinophils, mast cells), monocytes/macrophages, dendritic
cells
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Antimicrobial substances Produced by animals: Lysozyme
Peroxidase enzymes Lactoferrin Transferrin Defensins Produced by
your microbiota: Fatty acids Colicins Lactic acid
The Complement System Central feature = splitting of C3 C3a
& C3b Enzyme that splits C3 = C3 convertase C3 also
spontaneously degenerates to form C3a & C3b at a constant rate
Alternative pathway: C3b binds to foreign cell surface receptors
formation of C3 convertase Lectin pathway: pattern recognition
receptors = mannose binding lectins (MBLs): bind to mannose
molecules on microbial surface formation of C3 convertase Classical
pathway: antibody binds antigen = antigen-antibody complex
formation of C3 convertase (adaptive immune response)
The Acute Inflammatory Response Calor = heat: increased blood
flow to site Rumor = redness: increased blood flow Tumor =
swelling: fluid and cells accumulate Dolor = pain: pressure +
chemical mediators Functio laesa = loss of function: many possible
causes...
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The acute inflammatory response
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Leukocytes have to get out of the blood vessels:
recruitment
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The Adaptive Immune Response Primary response Secondary
response Humoral immunity: B cells, plasma cells, antibodies:
target extracellular pathogens Cell-mediated immunity T cells,
dendritic cells antigen is inside a cell
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Overview of the Adaptive Immune Response
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Lymphocytes CD4 = T helper lymphocytes Activate B cells,
macrophages and cytotoxic T cells Memory T cells CD8 = Cytotoxic T
lymphocytes B cells Nave Activated Mature = plasma cell (no longer
a dividing cell) Memory B cells
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How are B cells activated?
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What can happen when antibody binds antigen?
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MHC MHC class II molecules Expressed by antigen-presenting
cells Used to present exogenous (non-self) antigen MHC class I
molecules Expressed on the surface of all cells Used to present
endogenous (self) antigen Allows recognition and elimination of
infected cells viruses, intracellular bacteria
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Helper T cells recognize MHC Class II
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Cytotoxic T cells recognize MHC Class I markers
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What determines outcome of infection? Host defenses: functional
immune system? Age? Predisposing infection or other disease?
Injury? Pathogenicity of organism virulence factors; evasion or
invasion tactics? Infectious dose very large numbers of an organism
that is not very virulent will still be able to establish
infection; some organisms are so virulent that only a few organisms
are required to establish an infection
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Colonization 2 possible outcomes: Symbiosis Infection
Infection: Subclinical vs infectious disease Primary vs secondary
infection Opportunist vs primary pathogen
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Establishing infection Adherence Pili, capsules, cell wall
components binding to receptors on host cells Colonization Compete
for iron, nutrients Resist opsonization Resist residents
antimicrobials Secretion systems
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Exploitation of antigen sampling processes
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Avoiding host defenses Hide in cells Avoid complement- mediated
killing Avoid phagocytosis Survive in phagocytes Avoid
antibodies
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Disease: damage to host Damage caused by bacterial exotoxins
Proteins synthesized by bacteria Highly specific interactions with
host cells Highly immunogenic Toxoids Antitoxin
Cholera Etiologic agent: Vibrio cholerae Toxin: cholera toxin
Toxin type: A-B toxin Cell type with receptor: human
enterocytes
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Mechanisms of antimicrobial drugs Inhibition of cell wall
synthesis Inhibition of protein synthesis Inhibition of nucleic
acid synthesis Inhibition of biosynthetic pathways Disruption of
cell membrane integrity
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Mechanisms of acquired drug resistance Destruction or
inactivation of the drug: drug inactivation enzymes Alteration of
target molecule (mutation) Decreased uptake: alteration of porins
Increased elimination: efflux pumps
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Acquiring resistance Spontaneous mutation Gene transfer R
plasmids
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Genetics review Replication: duplication of the genome prior to
cell division Gene expression: decoding of DNA in order to
synthesize gene products (proteins): Transcription: DNA RNA
Translation: RNA protein
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Enzymes necessary for DNA replication Primase: synthesizes the
RNA primer DNA Polymerase: synthesize 53 DNA gyrase: releases
tension during uncoiling of circular DNA **target of quinolones and
aminocoumarins** DNA ligase: seals the gaps between Okazaki
fragments (forms covalent bonds) Helicase: unzips 2 strands of
DNA
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ESBL producers are resistant to all - lactam drugs: Penicillins
Cephalosporins Carbapenems Vancomycin Bacitracin
Antimicrobial resistance & antimicrobial stewardship
Remember the 4 Ds: Right Drug Right Dose De-escalation to
pathogen-targeted therapy Right Duration
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Vectors biological vector a vector in whose body the infecting
organism develops or multiplies before becoming infective to the
recipient individual. mechanical vector a vector which transmits an
infective organism from one host to another but which is not
essential to the life cycle of the parasite.
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But remember: The vast majority of microorganisms do not cause
disease We depend on our relationships with microorganisms for many
things
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Normal microbiota Protection Training of the immune system
Fermentation: beer, wine, cheese, yoghurt, bread, pickled
foods
