MICROBIOME AND PATHOGENESIS Flashcards
Microbiota
An individuals microbes, vary between site and individuals
Normal flora
Microbiota
Microbiome
Microbes and aggregate of microbial genomes in the microbiota
Core microbiome
Commonly shared species at a specific site
Secondary microbiome
Species that contribute to diversity in an individual
Describe gut microbiota
Highest number of organisms in bodily niche
Seeded at birth - affected by child delivery option
Rapidly diversified
Typical adult profile within first few years of life
Common phyla include Firmicutes and Bacteroidetes
What are roles of the microbiome?
Digestion, producing vitamins and minerals
Protect against pathogens
Regulate immune system
Possibly contribute to mood and behaviour
Structure of a virus
Lack cytoplasm
Proteins synthesised on host ribosomes
Describe prokaryotes structure
Lack cytoskeleton
Shape determined by cell wall
Describe eukaryotes structure
Cytoskeleton
Complex internal structure
Arches like information processing
Bacteria like metabolism
Describe archaea structure
Ether linked membrane lipids
Unique metabolic features
Describe bacteria structure
Eater linked membrane lipids
Peptidoglycan cell wall
Describe the cell wall
Main load bearing structure
Resists osmotic pressure and determines cell shape
Peptidoglycan (Murien) - polysaccharide chains with peptide cross links
Signal to innate immune system of bacterial presence
Describe the gram positive bacteria cell wall
Thick cell wall made up of many layers of murein.
Several constituents (teichoic acids, lipoteichoic acids and protein) protrude from this layer
Describe the structure of the gram negative bacterial cell wall
Thin cell wall and outer membrane
Outer leaflet of the outer membrane is made up of lipopolysaccharide
Space between the 2 membranes is the periplasm.
Describe peptidoglycan structure
Alternating N-acetylglucosamine and N-acetyl-muramic acid
Peptide cross links attached to NAM residues
It is thick (20-25 layers) in gram positive bacteria
It is thin (1-3 layers) in gram negative bacteria
What is the peptidoglycan arrangement in gram positive bacteria?
It was previously assumed that it would be in multiple layers but now evidence exists that it is wound into cables which are wrapped around the cell
Describes the peptidoglycan arrangement in gram negative rods
Polysaccharide chains wrapped around the circumference of cell, peptide cross links parallel to cell axis
Describe the cell membrane
It is a phospholipid bilayer
It is the main permeability barrier
Describe capsules
Amorphous polysaccharide slime surrounding cell
Presence and composition strain - specific
Environment - prevents desiccation
In animal hosts : inhibits phagocytosis
Attachment to surfaces
Describe the structure and function of flagella
Generate thrust by rotation at 200-1000 rpm
Attached via hook and basal body containing motor proteins (driven by proton gradient) and switch proteins (control direction of rotation)
Describe pili and fimbriae
Protein spikes used to attach to surfaces
Type 1 fimbriae required for pathogenic Escherichia Coli strains to adhere to urethra to cause UTI
Sex Loki involved in DNA transfer in conjugation
What are the 4 basic viral forms
Icosahedral nucleocapsid
Enveloped icosahedron
Helical, non enveloped
Helical, enveloped
Describe the structures in a icosahedral nucleocapsid virus
Capsomeres (proteins)
Nucleic acid
Describe the structures in an enveloped icosahedron virus
Nucleic acid
Envelope consists of phospholipid and glycoproteins
Describe the structures of the helical non enveloped virus
Nucleic acid
Proteins
Describe the structures in the helical enveloped virus
Nucleic acid
Envelope: phospholipid and glycoprotein
How are virus’ classified?
By the presence/absence of the envelope
By The type of nucleic acid present is the Baltimore classification
What are the viral forms?
RNA viruses
DNA viruses
Describe the viral lifecycle
Attachment and entry to host
Uncoating
Replication
Assembly and maturation
Released by budding
What is commensalism?
One of the 2 organisms in a relationship benefits. The other doesn’t gain and isn’t harmed
What is mutualism?
Both partners in a relationship gain
What is parasitism?
Where one organism in the relationship gains at the expense of the other
What is a pathogen?
Organisms or infectious agents which cause disease
Pathogenesis
The mechanism by which a disease is produced
Pathogenicity
Ability of an organism to cause disease
Virulence
The relative ability of a pathogen to cause disease
Infection
Invasion of microorganisms into a host
Infectivity
The ability of a microbe to enter, survive in and multiply in a susceptible host
Infectious disease
When infection leads to host damage and injury
Epidemic
Unusually high number of cases at a particular time
E.g. plague
Endemic
Always present
E.g. gonorrhoea
Pandemic
Worldwide
E.g. influenza
Acute
Quick
E.g. measles
Chronic
Slow
E.g. tuberculosis
Specific
E.g. smallpox
Non-specific
E.g. wound infection
What is the chain of infection
Characteristics of the organism (pathogen)
Portal of entry
Reservoir
Portal of Exit
Mode of transmission
Characteristics of the host
What are characteristics of the organism (pathogen)?
Type Ability to invade host Virulence Degree to which it causes disease Number of organisms
What are possible portals of entry
Eyes Mucous membranes Respiratory tract Placenta Breaks in host barriers
What are possible reservoirs?
Humans
Animals
Environmental surfaces
What are possible portals of exit?
Respiratory tract Genitourinary tract Gastrointestinal tract Skin/mucosal surfaces Placenta Blood
What are possible modes of transmission?
Direct contact
Droplets
Vectors
Airborne
What are possible characteristics of the host?
Lack of effective resistance
Changes in host defences
Tissues destruction
What are possible sources of infection?
Endogenous:
- from the host itself
Exogenous:
- from people (cases, carriers)
- from animals (zoonoses) e.g. plague from rabies
- from the environment e.g. legionella from water, tetanus from soil
What are the possible routes of spreading infection through horizontal transmission?
To other people:
- airborne e.g. influenza, colds, TB
- faecal-oral e.g. food poisoning, typhoid
- sexual contact e.g. gonorrhoea, HIV
- vectors e.g. mosquitos carry malaria
- animals e.g. rabies
Indirect transmission:
-fomites
What are the possible ways of spreading infection through vertical transmission?
Mother to child e.g. HIV, rubella
What are possible virulence factors?
Adhesins Bacterial toxins - exotoxins and endotoxins Invasiveness Cell damage Avoid immune response
Describe exotoxins
May be the principal cause of disease
Proteins produced by gram positive and gram negative bacteria
Many consist of a number of subunits
Secreted into the extracellular space
Differing modes of action - cytotoxic, enterotoxic, neurotoxic
Describe clostridium and clostridial neurotoxins
Anaerobic, spore forming organisms
Ubiquitous in the environment
Very potent molecules
Affect peripheral nervous system
Clostridium botulinum causes botulism. It produces one of seven toxins - A B C D E F G (BoNT/A and so on)
Clostridium tetani causes tetanus (lockjaw). It produces one toxin - TeNT
Describe tetanus
Can be neonatal and maternal
Results from wound infection
Causes muscle rigidity and spasm
Describe botulism
Caused by food poisoning - ingestion of pre formed toxin
Caused by wounds - introduction of spores
Infant botulism can occur
Causes descending flaccid paralysis
In babies it results in a failure to feed
Describe the structure of a neurotoxin
It is a tripartite toxin - it has 3 parts:
The protease which is the active subunit
The translocation unit
The binding domain
How does botulism result in flaccid paralysis?
The BoNTs act at the neuromuscular junction
How does tetanus cause muscle spasms and then paralysis?
TeNT enters at the neuromuscular junction and is transported to the spinal cord where it acts within inhibitory interneurons
What are possible toxin modifications?
Chimera - results in binding to different target cells
Delivery vehicle - causes inactivated protease. Carry drugs or other molecules into cells
Non paralytic - enters central neurone