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Biology 260: Review for Final

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Biology 260: Review for Final. Microorganisms. Bacteria: unicellular prokaryotic organisms; extremely diverse, adapted to essentially all habitats Fungi: unicellular or multicellular eukaryotic organisms Protozoa: unicellular eukaryotic organisms - PowerPoint PPT Presentation
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Biology 260: Review for Final
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Page 1: Biology 260: Review for Final

Biology 260: Review for Final

Page 2: Biology 260: Review for Final

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

Page 3: Biology 260: Review for Final

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

Page 4: Biology 260: Review for Final

Cell type Cell wall? Cell membrane?

Bacteria Prokaryotic Yes Yes

Fungi Eukaryotic Yes Yes

Protozoa Eukaryotic No Yes

Algae Eukaryotic Yes Yes

Page 5: Biology 260: Review for Final

Cell type DNA Organelles Nucleus Cell membrane

Ribosomes

Prokaryotic Double stranded

No No Yes 70s (50s + 30s)

Eukaryotic Double stranded

Yes Yes Yes 80s (60s + 40s)

Page 6: Biology 260: Review for Final

Bacterial Structures

Page 7: Biology 260: Review for Final

Cell Wall Gram-positive

Thick layer of peptidoglycanTeichoic acids

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Cell WallGram-negative

Thin layer of peptidoglycanOuter membrane - additional membrane barrier

Lipopolysaccharide (LPS)

O antigen

Core polysaccharide

Lipid A

Page 9: Biology 260: Review for Final

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

Page 10: Biology 260: Review for Final

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 cell’s energy currency)• Rotation of flagella (motility)• One form of active transport across the membrane

Cytoplasmic membrane

Electron transport chain

Page 11: Biology 260: Review for Final

Internal structures: Ribosomes

Page 12: Biology 260: Review for Final

Unique molecules in bacteria can be used as targets for chemotherapy

• Cell wall: peptidoglycan, techoic acid• Ribosomes• Unique biosynthetic pathways

Page 13: Biology 260: Review for Final
Page 14: Biology 260: Review for Final

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)

Page 15: Biology 260: Review for Final

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

Page 16: Biology 260: Review for Final

Primary and Secondary metabolites

Page 17: Biology 260: Review for Final

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

Page 19: Biology 260: Review for Final

Innate immune system

• 1st line defenses: skin, mucosal barriers, secretions - antimicrobials (lysozyme), iron-binding proteins (transferrin)

• Complement system• Granulocytes (neutrophils, eosinophils, mast

cells), monocytes/macrophages, dendritic cells

Page 20: Biology 260: Review for Final

Antimicrobial substances

• Produced by animals:– Lysozyme– Peroxidase enzymes– Lactoferrin– Transferrin– Defensins

• Produced by your microbiota:– Fatty acids– Colicins– Lactic acid

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Immune Defenses

• Sensory systems:– Pattern recognition receptors

• Toll-like receptors• NOD-like receptors• RIG-like receptors

– Complement system• Alternative pathway• Classical pathway• Lectin pathway

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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)

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Page 24: Biology 260: Review for Final

Leukocytes

• Phagocytes: macrophages & neutrophils• Antigen presenting cells• Natural killer cells

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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

Page 27: Biology 260: Review for Final

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

Page 29: Biology 260: Review for Final

Overview of the Adaptive Immune Response

Page 30: Biology 260: Review for Final

Lymphocytes

• CD4 = T helper lymphocytes– Activate B cells, macrophages and cytotoxic T cells– Memory T cells

• CD8 = Cytotoxic T lymphocytes• B cells

– Naïve– 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

Page 34: Biology 260: Review for Final

Helper T cells recognize MHC Class II

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Cytotoxic T cells recognize MHC Class I markers

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Page 37: Biology 260: Review for Final

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 resident’s

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

Page 43: Biology 260: Review for Final

Diseases caused by exotoxins• Neurotoxins

– Botulism– Tetanus

• Entereotoxins– Cholera– Traveler’s diarrhea

• Cytotoxins– Anthrax– Pertussus (whooping cough)– Diptheria– Hemolytic uremic syndrome– Dystentery

• Membrane-damaging toxins:– Gas gangrene– Strep throat– Abscesses

• Superantigens– Some foodborne

intoxications– Toxic shock syndromes

Page 44: Biology 260: Review for Final

CholeraEtiologic agent: Vibrio

choleraeToxin: cholera toxinToxin type: A-B toxinCell 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

Page 46: Biology 260: Review for Final

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

Page 47: Biology 260: Review for Final

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 →RNATranslation: RNA → protein

Page 49: Biology 260: Review for Final

Enzymes necessary for DNA replication

• Primase: synthesizes the RNA primer• DNA Polymerase: synthesize 5’→3’• 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

Page 50: Biology 260: Review for Final

ESBL producers are resistant to all β-lactam drugs:

• Penicillins• Cephalosporins• Carbapenems• Vancomycin• Bacitracin

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Emerging drug resistance

• MRSA: Methicillin-resistant Staphylococcus aureus

• Drug-resistant Mycobacterium tuberculosis• ESBL producers (enterobacteria,

enterococccus)• Vancomycin-resistant enterococcus

Page 52: Biology 260: Review for Final

Antimicrobial resistance & antimicrobial stewardship

• Remember the 4 D’s:– Right Drug– Right Dose– De-escalation to pathogen-targeted therapy– Right Duration

Page 53: Biology 260: Review for Final

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.

Page 54: Biology 260: Review for Final

• Normal microbiota– Protection– Training of the immune system

• Fermentation: beer, wine, cheese, yoghurt, bread, pickled foods


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