In-depth notes on 5BBBMB28 Medical Microbiology written post rewatching lectures, containing all content and extra information where information given in lecture wasn't clear
L02: Principles of bacterial pathogenies
• Microorganisms were the first to understand how host processes work
• Important to study virus in order to understand how to target them (mechanism by
which they cause disease)
• Plague is caused by yersinia pestis- caused major pandemics throughout history
• Pathogens are evolving antibiotic resistance genes/strains
• As many bacteria in gut as cells
• Bacteria are prokaryotes, therefore they have no nucleus, therefore their genetic
material is located in a circular piece of DNA called a chromosome
• Many bacteria, especially pathogens also have circular pieces of DNA called
plasmids. Plasmids can be transmitted between bacteria. Can carry virulence
genes
• Bacteria can be characterised as gram-negative or gram-positive and that is
determined by the nature of their cell wall On top of the cell wall, multiple bacteria
have sugar (polysaccharide) coating called capsule- immune invasion structure
• Several bacterium have flagellum which aids in movements
• Pili/ Fimbriae are used to aid adhesion to surfaces as well as conduits to inject
plasmids into other bacteria
• Gram-ve and gram+ve depends on their ability to accumulate a dye called gram
stain. The reason for the difference in accumulation of the dye is due to the
peptidoglycan (layer of sugar on the surface of bacteria)
• Gram+ve bacteria only have one membrane which is surrounded by a thick
coating of the peptidoglycan, so when exposed to that dye they become purple
• Gram-ve bacteria have two membranes (outer and inner membrane) separated
by a layer of peptidoglycan so when exposed to the gram stain they don’t
accumulated it and are just pink
• Testing with gram stain is very rapid process and is often used in diagnosis lab in
order to understand the type of bacteria that is affecting a patient
• Bacteria are also characterized based on their shape (5 different shapes)
o Spherical- streptococcus
o Rod- salmonella
o Spiral- H. pylori
o Comma- Vibrio Cholerae
o Corkscrew- Treponema palidum
• The shape of the bacteria under a microscope allows for a diagnostics
• Diagnosis of bacterium responsible for infection
o Classify symptoms
o Sample of tissue infected
o Culture
o Antibody tests
o Antigen test- most direct
o Microscope (use gram stain, shapes, look at behaviour of bacteria)
o Genetics= PCR, sequencing
, • Bacteria can attach as single cells, pairs, chains and clusters. For example,
Salmonella will never be found as a chain
• Koch postulates- what makes a bacteria a pathogen. establish a causal
relationship between a microbe and a disease
• 4 principles used to determine if a patient is affected by a specific pathogen =
Koch’s postulates
o Need to find the presence of the microorganism in all the individuals
with the disease but not a healthy individual- blood sample with virus vs
clean blood sample
o The microorganism must be grown in culture form diseases individuals
only
o Inoculation (infection) of a healthy, susceptible individual with the
cultured microorganisms must recapitulate the disease
o The microorganisms must be re-isolated form the inoculate, diseases
individual and matched to the original microorganism
• Koch postulates process can’t be done in people (not ethical)
• Limitations of Koch postulates:
o Asymptotic carriers Commented [MN1]: asked faq about why-
o Some bacteria can’t grow alone asking clarification
• Bacteria can be divided into strict pathogens or opportunistic pathogens
• Strict pathogens are always associated with the disease, need the host to
replicate. Usually not very efficient at replicating in the environment- Example:
Shigella and tuberculosis
• Opportunistic pathogen can be commensal (uses food supplied in the internal
or the external environment of the host, without establishing a close
association with the host) but will accidentally cause infections in
immunocompromised individuals. This pathogens (bacteria) have not
developed to cause disease in people – Example: pseudomonas aeruginosa
in cystic fibrosis patients
• Criteria that make bacterium and pathogen: all achieved through virulence
factors
o Infect/invade the host
o Grown on or in the host
o Be transmitted to a new host- through coughing
o Evade host defences
o Damage the host – damage is what leads to disease
• Virulent of an organism is measured by ID50 (50% infectious does) and LD50
(50% lethal dose)
• The lower the LD50, the more pathogenic a strain in- less bacteria are needed
to infect- more potent
• Different strain of the same species of bacteria can be more or less virulent
• Bacterial pathogens have different modes of transmission:
o Oral- food borne agents- salmonella
o Respiratory- Diphtheria
o Cutaneous- Rickettsia
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, o Transcutaneous- clostridium tetani
o Sexual- chlamydia
• Transmission can be direct or indirect. Direct – person to person or animal or
person- salmonella. Indirect – surfaces (biofilm replication)- example:
c.difficile
• Virulence factors allow bacteria to:
o Invade and colonize host
▪ Adhesion and invasion factors
o Cause disease
▪ Toxins
o Evade host defences
▪ Capsule
▪ T3SS effectors and inhibit immune signalling and phagocytosis
• The pathogen invades the host via adhesions factors- helps with colonisation
of the tissue
• Invasion factors are particular important for intracellular bacteria that need to
replicate within host cells. Factors allows their entry into the cells
• Secretion systems main function act as needle to inject virulence factors
• Virulence factors are often encoded on pathogenicity islands (PAI)
• PAI are a cluster of genes acquires through horizontal gene transfer between
bacteria found in both on chromosome and plasmids
• PAI are found in pathogenic strains but absent in non-pathogenic strains of
the same species
• PAIs carry genes encoding one or more virulence factors such as toxins,
adhesion and secretion systems and their effectors
• Adherence factors initiate colonization and are mediated by adhesions
including fimbriae. Adherence factors determine the site of colonization
o Yersinia species infect different sites and cause different diseases
(plague or gastroenteritis)
• Toxins of bacteria are main determinant of disease. Toxins alter the normal
metabolism of host cells and are crucial por pathogenies
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, • There are different types of toxins: exotoxins, endotoxins and type III
cytotoxins.
• Exotoxins- secreted proteins
• Endotoxins- on the surface of bacteria- LPS
• Type III cytotoxins- effector protein injected by secretion system directly into
host cells
• Endotoxin (LPS) is not secreted as it’s located at the surface of gram-ve
bacteria cell wall
• LPS in nature is not toxic, but by binding to its receptor TLR4 (PRR) present
in macrophages leads to a strong upregulation of pro-inflammatory cytokines
• In the presence of gram-ve bacteria in blood, there’s an uncontrolled
upregulation of cytokines which can trigger septic shock
• Examples of of exotoxins:
o AB toxins
o Pore forming toxins
o Neurotoxins
• AB exotoxins are complex of two components A (active) and B (binding).
o B subunit medicates binding with binding site of the host cell aiding the
process of endocytosis by the host cells
o After endocytosis the A subunit is secreted, which it can then exert its
different function
• The A subunits of AB exotoxins different between different pathogens
o Diphteria toxin induce cell death by inhibiting protein synthesis
o Cholera toxin modifies receptors on the surface of host cells leading to
the secretion of water and ions in the intestinal lumen causing
diarrhoea
• Pore forming exotoxins are secreted as monomers and upon binding to
receptor in the surface of host cell, they oligomerize into a pore. The creation
of the pore affects the homesostias of the cell and the integrity of the
membrane, allowing passage of water and ions leading to cell death
(example: streptolysin O from group A streptococcus which kills red blood
cells) as well as tissue damage as tissue is no longer permeable
• LLO toxin derived from listeria also use pore forming toxins by inserts itself
into the vacuole that surrounds the bacteria when in transition. LLO generates
disruption and lysis in the vacuole allowing the bacteria to be freed and be
alone in the cytosol and therefore able to easily replicate
• Neurotoxins affect the nervous system. Usually are transported from the
peripheral nervous system into the central nervous system through retrograde
transport on axons affecting the brain by the way muscles work
• Two examples of neurotoxins are: botulinum toxin and tetanus toxin
• Botulinum toxin relaxes the muscles, but has also been used for clinical use:
treat muscle spasms and cosmetic application
• Tetanus toxin- induces muscle contraction in the jaw, in the face and it can
also effect all muscles
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