
HC13: Bacteria
Complexity
The complexity of an organism is based on its amount of base pairs:
- Prion: 103base pairs
- A single protein
- Virus: 104-5base pairs
- A set of proteins and nucleic acid
- Uses living cells
- 0,03-0,3 mm
- Made visible with an electron microscope
- Bacterium: 106base pairs
- A single cell prokaryote
- 0,1-10 mm
- Made visible with a light microscope
- Protozoa: 107base pairs
- A single cell eukaryote
- 4-10 mm
- Made visible with a light microscope
- Fungi: 108base pairs
- A multi-cellular eukaryote
- 4-10 mm
- Made visible with a light microscope
- Helminths: 109base pairs
- A multi-cellular eukaryote
- Approximately 40 mm
- Visible with the unaided human eye
Bacteria are the oldest form of life on earth. Bacteria are called prokaryotes because they don't have a nucleus. Millions can fit into the eye of a needle. Most live by themselves, but some in symbiosis. A bacterium doesn't have a nucleus or cell organelles. Bacteria can adapt to their surroundings very well.
Composition
Eukaryotes:
A eukaryotic cell has a:
- Membrane
- Cytoplasm with organelles
- Nucleus with DNA
Eukaryotic pathogens are protozoa, fungi and helminths.
Prokaryotes:
A prokaryotic cell, like a bacterium lacks a nucleus and cells organelles, but does consist of:
- DNA and RNA in the form of a ring
- Plasma membrane
- Mainly ribosomes are present in the cytoplasm
- Most (but not all) contain a cell wall
- Plays a part in the immune response → the target of antibiotics
- Protects the bacterium from its environment
- Contains:
- Capsule
- Flagella → for movement
- Pili → for attachment
- Plays a part in the immune response → the target of antibiotics
The cell wall is very important for bacteria:
- Protects against the environment
- Has antigenic properties → targeted by the immune response
- Has a role in pathogenesis
- Is relevant in diagnostics
Classification of bacteria
Classification based on cell wall composition:
Gram stains can be used to look at the cell walls of bacteria. A bacterium can be gram positive or gram negative:
- No cell wall → mycoplasma
- Gram staining cannot be used
- Gram positive → streptococcus pyogenes
- Keep their purple staining
- Gram negative → escherichia coli
- Lose the purple staining, are counterstained and become pink
- Acid-fast → mycobacterium tuberculosis
- The cell wall is so tight it cannot be colored with gram stains
Most bacteria are either gram-positive or negative. Whether a bacterium is gram-positive or negative is based on fundamental differences in their cell wall:
- Gram-positive bacteria
- Peptidoglycan on the outside
- This forms the actual cell wall
- Plasma membrane on the inside
- A lipid bilayer
- Lipoteichoic and teichoic acids sticking out of the cell wall
- More resistant to environmental conditions
- More difficult to kill with detergents
- Peptidoglycan on the outside
- Gram-negative bacteria
- Cell wall
- An outer membrane
- Many proteins can do this
- Periplasmic space: between the outer membrane and the peptidoglycan
- Peptidoglycan
- An outer membrane
- A plasma membrane on the inside
- A lipid bilayer
- LPS
- More susceptible to environmental conditions
- Easier to kill with lipophilic detergentia
- Sensitive to:
- Ethanol or propanol 70-95%
- Chlorhexidine 0,05-0,5%
- Ammonium, phenol
- Chlorine and iodine
- Cell wall
Peptidoglycan:
Peptidoglycan is part of the cell-wall of gram-positive bacteria. It also is present in gram-negative bacteria, but as a very thin layer. It is composed of long chains of polysaccharides cross-linked by peptides. Peptidoglycans ensure that the purple staining remains in the bacteria. It is a stimulator of immune responses:
- TLRs (toll-like receptors) recognize peptidoglycan
- Granulocytes and macrophages start to release interleukin and many other cytokines
- IL-1
- IL-6
- TNF
- Inflammation, fever and shock follow
Many antibiotics for gram-positive bacteria work by disrupting the peptidoglycan layer.
Lipo-polysaccharides:
Lipo-polysaccharide (LPS) is present in gram-negative bacteria. They are the gram-negative counterparts of the lipoteichoic and teichoic acids in gram-positive bacteria. It also is a stimulator of immune responses:
- LPS interacts with Toll-like receptors
- Granulocytes and macrophages start to release interleukin and many other cytokines
- IL-1
- IL-6
- TNF
- Inflammation, fever and shock follow
Classification based on shape:
A bacterium can roughly have 2 different shapes:
- Cocci (round)
- Rod (elongated)
The shape can be distinguished further in:
- Curved
- Spirochete
The most common classification system of bacteria is based on shape and gram negative/positive:
- Gram negative
- Curved → vibrio campylobacter
- Rods → escherichia
- For example salmonella
- Cocci → neisseria
- Spherical
- Gram-positive
- Rods
- Spore forming → clostridium and bacilus
- Non spore forming
- Cocci
- Groups → staphylococci
- Multiply in all directions
- Chains → streptococci
- Multiply in only 1 direction
- Groups → staphylococci
- Rods
Classification based on growth:
Bacteria grow by either following an aerobic or an anaerobic route:
- Aerobic: in the presence of oxygen
- Anaerobic route: deep in the ocean or in the human bowel
Some bacteria can survive in both conditions. If anaerobic bacteria are found in a blood sample, this indicates that there's an infection somewhere in the body where there isn't any oxygen.
Aspects can be shown on a culture plate:
- a-hemolytic: partial hemolytic
- Greenish
- b-hemolytic: fully hemolytic
- Yellowish
- Non-hemolytic
Hemolytic bacteria can cause lysis in erythrocytes.
Extracellular versus intracellular:
Bacteria can be extracellular or intracellular:
- Extracellular bacteria are phagocytosed
- Site of infection:
- Interstitial spaces
- Blood
- Lymph
- Epithelial surfaces
- Site of infection:
- Intracellular bacteria can survive inside the cell
- Site of infection:
- Cytoplasmic
- Vesicular
- For example TBC or salmonella
- Site of infection:
Bacterial spores
Some gram-positive bacteria are capable of sporogenesis, for example the clostridium species. Spores can infect easily and are hard to eradicate. A bacterium becomes a spore when it's exposed to a warm, humid environment. A bacterial spore is a dehydrated structure with a thick wall, in which the bacterium is in a dormant state. It can survive extreme environmental conditions → they are hard to kill. To get rid of a spore, disinfectants and pasteurization won't work.
Bacterial capsules
A bacterial capsule is a polysaccharide surrounding the cell wall, which may be present in both gram positive and gram-negative bacteria. It prevents complement-dependent phagocytosis. Vaccines for capsules induce capsule-specific antibodies. Currently, vaccines are available for:
- Streptococcus pneumoniae
- Neisseria meningitidis
- Haemophilus influenzae B
These diseases can all cause meningitis.
Replication and genetics
A bacterium has 1, usually circular, chromosome. Division takes place by binary fission → the cell is divided in 2:
- The bacterium replicates its DNA
- The cell wall is cut
- There are 2 bacteria
This is a form of asexual reproduction and takes only 20 minutes.
Plasmids:
Plasmids are extra pieces of bacterial circular DNA. Plasmids are relevant because bacteria can share plasmids. They replicate independently from chromosomal DNA and convey additional properties:
- Antibiotic resistance
- Toxin production
- Metabolism of additional substrates
Once plasmids have integrated into the chromosome, they stay there permanently. If this hasn't happened yet, the plasmid is still in a circle form and it can be exchanged between bacteria.
Change:
The DNA properties of bacteria can change. Because bacteria replicate so fast, errors are made easily:
- Mutation
- This occurs sporadically
- Exchange of DNA
- Transformation: uptake of free DNA and integration into a chromosome
- Transduction: a bacteriophage (bacterial virus-DNA) is absorbed by bacteria-DNA → the bacteria changes
- A bacterial virus may carry resistant or toxin-producing genes
- Conjugation: transfer of the plasmid DNA via pili
- Selection pressure
- Determines the relevancy for humans
- If there wouldn't be any selection pressure, bacteria would lose their resistant genes
- Selection pressure is the cause of resistance to antibiotics
Effects
Bacteria have negative and positive effects:
- Negative aspects
- Infectious diseases
- Intoxications
- Unpleasant smells
- Et cetera
- Positive aspects
- Food production
- Probiotics
- Medication
- Antibiotics
- Vaccines
- Protein drugs
- Water purification
- Fuel production
- Methanol
- Ethanol
- Nitrogen fixation
- N2removal from the environment and conversion to ammonia for use by plants
- Oxygen production
- 50% of oxygen is produced by the cyanobacteria
- Breakdown of dead organic matter
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Mechanisms of Disease 1 2020/2021 UL
- Mechanisms of Disease 1 HC1: Introduction to G2MD1
- Mechanisms of Disease 1 HC2: Introduction to the immune system
- Mechanisms of Disease 1 HC3: Innate and adaptive immune responses & key cytokines
- Mechanisms of Disease 1 HC4: Pathology of normal immune response
- Mechanisms of Disease 1 HC5: B- and T-cell generation and diversity
- Mechanisms of Disease 1 HC6: Mechanisms of adaptive immunity
- Mechanisms of Disease 1 HC7: Effector mechanisms of antibodies
- Mechanisms of Disease 1 HC8: B-cell development and antibodies
- Mechanisms of Disease 1 HC9: Tissue injury and repair
- Mechanisms of Disease 1 HC10: Repair mechanism
- Mechanisms of Disease 1 HC11: Pathology of inflammatory reactions
- Mechanisms of Disease 1 HC12: Introduction to infectious diseases
- Mechanisms of Disease 1 HC13: Bacteria
- Mechanisms of Disease 1 HC14: Viruses
- Mechanisms of Disease 1 HC15: Fungi and parasites
- Mechanisms of Disease 1 HC16: Invaders
- Mechanisms of Disease 1 HC17: Host versus invader
- Mechanisms of Disease 1 HC18: Immune deficiencies and infection risk
- Mechanisms of Disease 1 HC19: Pathology of infectious diseases
- Mechanisms of Disease 1 HC20: Diagnostics of infectious diseases
- Mechanisms of Disease 1 HC21: Essential microorganisms
- Mechanisms of Disease 1 HC extra: Mycobacterial infections (tuberculosis)
- Mechanisms of Disease 1 HC22: Antimicrobial therapy
- Mechanisms of Disease 1 HC23: Principles of antibiotic pharmacotherapy
- Mechanisms of Disease 1 HC24: Introduction MOOC
- Mechanisms of Disease 1 HC25: Epidemiology
- Mechanisms of Disease 1 HC26: Prevention and control
- Mechanisms of Disease 1 HC extra: COVID-19
- Mechanisms of Disease 1 HC27: Mechanisms of hypersensitivity reactions
- Mechanisms of disease 1 HC28: Pathology of allergy
- Mechanisms of Disease 1 HC29: Asthma
- Mechanisms of Disease 1 HC30: Pathology of autoimmunity
- Mechanisms of Disease 1 HC31: HLA and autoimmunity
- Mechanisms of Disease 1 HC32: Vasculitis
- Mechanisms of Disease 1 HC33: Systemic Lupus Erythematosus
- Mechanisms of Disease 1 HC35: Infections and autoimmunity
- Mechanisms of Disease 1 HC36: Immune cells in rheumatoid arthritis
- Mechanisms of Disease 1 HC37+38: Pharmacology: immunosuppression
- Mechanisms of Disease 1 HC39: Pathology of transplantation

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Mechanisms of Disease 1 2020/2021 UL
Deze bundel bevat aantekeningen van alle hoorcolleges van het blok Mechanisms of Disease 1 van de studie Geneeskunde aan de Universiteit Leiden, collegejaar 2020/2021.
This bundle contains notes of all lectures from the module Mechanisms of Disease 1, Medicine, Leiden
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