Microbial Pathogens Flashcards
What are the most common bacteria on our skin?
Staphylococcus, Streptococcus, Corynebacterium
They colonise warm, sheltered places and metabolise sweat
Biofilms, 300 to 500 cells thick on teeth are composed of mainly…
Streptococcus sanguis and Streptococcus mutans
Bacteria in the gut are essential for..
Breaking down carbohydrates, producing essential nutrients (Vit K & B12) and crowding out harmful bacteria
How much of our genome consists of fossil viruses?
About 1/12
What are the points of Koch’s Postulate?
- The microorganism must always be found in similarly diseased animals, but not in healthy ones.
- The microorganism must be isolated from a diseased animal and grown in pure culture.
- The isolated microorganism must cause the original disease when inoculated in a susceptible host
- The microorganism must be re-isolated from the experimentally infected animals.
What are the issues with Koch’s Postulate?
- Animal may be asymptomatically carrying
- Some microorganisms cannot/are hard to grow in culture
- The isolated microorganism should cause original disease upon inoculation but does not always
Symbiosis
Organisms live together in close association
Mutualism
Beneficial to both symbionts
Neutralism
Neither symbiont is affected by the relationship
Commensalism
Beneficial to only one symbiont
Parasitism
Harmful to one (host), beneficial to other (parasite)
Synergism
Two or more microorganisms team up to cause disease. Also called polymicrobial infection
Pathogen
Microorganism that causes diease (<3% of all)
Opportunistic Pathogen
Has the potential to cause disease
What are the periods in the course of an infectious disease?
Incubation Period - time between infection and onset of symptoms
Prodromal Period - patient feels out of sorts, but experiences no symptoms
Illness - experience of symptoms associated with the disease
Convalescent Period - time during which the patient recovers
What are the types of human carriers of disease?
Passive Carrier - carries pathogen but has never had disease symptoms
Incubatory Carrier - patient is in incubation period (asymptomatic)
Convalescent Carrier - patient recovering from disease, but still carrying pathogen
Active Carrier - patient has completely recovered, but still carries pathogen
What are the 6 types of infection?
Localised - pathogens are contained at the site of infection
Systemic - pathogen spreads throughout the body
Acute - rapid onset, rapid recovery
Chronic - slow onset, slow recovery
Latent - pathogen not completely eradicated after recovery and can cause symptoms in future
Secondary - disease that follows primary infection
What is the difference between an infectious disease and microbial intoxication?
In an infectious disease a pathogen colonises hos body and causes disease. In microbial intoxication a pathogen is produced in vitro and toxins are ingested to cause disease - this is often more rapid in onset and recovery than the former
Steps in pathogenesis of infectious disease
- Entry
- Attachment
- Multiplication
- Invasion or spread
- Evasion of host defenses
- Damage to host tissue
What are some virulence factors
- Promote attachment to host cells (adhesins)
- Help bacterium to enter host cell (invasins)
- Damage host cell or tissue (e.g. cytolysins)
- Over-stimulate immune response (immunopathogenic factors)
- Mediate immune evasion
What are some immune evasion factors?
- Capsules (prevent opsonisation and phagocytosis)
- Destruction of phagocytes
- Inhibition of phagocyte chemotaxis
- Inhibition of phagocytosis
- Destruction of complement factors
- Destruction of immunoglobulins
- Intracellular replication
What are some reasons that disease isn’t always observed?
- Unable to grow at site of contact
- Absence of colonising host receptors
- Antibacterial factors (e.g. lysozyme in tears)
- Microbial antagonism - indigenous bacteria use all nutrients/antibacterial factors
- Health status
- Immunity
- Elimination by immune system
Bacterial that are ingested
Salmonella, Campylobacter, Shigella, E. Coli, Vibrio
Bacterial that are inhalated
Legionella, Streptococcus, M. pneumoniae, Bordetella
Bacterial that infect via trauma
Clostridium tetani
Bacterial that infect via needlestick
Staphylococcus aureus, Pseudomonas
Bacterial that infect via arthropod bite
Rickettsia, Coxiella, Borrelia, Yersinia pestis, Francisella
Bacterial that infect via sexual transmission
Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum
What are 4 basic mechanisms of immune evasion?
- Disguise - surface molecules, antigenic variation
- Hide - invasion of host cells, biofilms)
- Fool - de-regulating immune responses
- Attack - destruction of immune components
what are some examples of CAMPs?
alpha-Defensin hNP-1 beta-Defensin hBD1 Cathelicidin LL-37 Thrombocidin TC1 Dermcidin
What are some antimicrobial host factors and what charge are they?
- Positively charged
- Antimicrobial peptides
- Lactoferrin
- Lysozyme
- Myeloperoxidase
What are some features of the bacterial cell envelope and what charge are they?
- Negatively charged
- Peptidoglycans
- Teichoic Acids
- Lipoteichoic Acids
- Lipid A
- LPS
What are 4 mechisms of CAMP resistance in bacteria?
- Repulsion of CAMP (Modification of TA or Lipia A - Staph, Strep, Salmonella, Pseudomonas)
- Extrusion of CAMP (MtrCDE efflux pump - Neisseria)
- Neutralisation of CAMP (Staphylokinase, SIC - Staph, Strep)
- Cleavage of CAMP (PgtE proteases - E. Coli, Salmonella)
What are the 3 forms of complement evasion by bacteria?
- Modulation or inhibition of complement proteins
- Inactivation by enzymatic degradation
- Recruitment or mimicking of complement regulators
What are some ways bacteria modulate or inhibit complement proteins?
- Staphylococcal complement Inhibitor (SCIN) binds to C3 convertases and inhibits its activation
- Streptococcal inhibitor of complement (SIC) binds to C5c-C7/C8 and prevents the formation of MAC. MAC is ineffective against gram positive bacteria like Strep so this mechanism is confusing
- Staphylococcal protein A (SpA) is found on the bacterial cell surface and binds the Fc regin of IgG which prevents opsonisation and the classical pathway
- Chemotaxis inhibitory protein of Staph Aureus (CHIP) binds to C5a receptor and inhibits its chemotactic signalling
What are some ways bacteria inactivate complement by enzymatic degradation?
- Pseudomonas proteases cleave C3 and prevent C3b opsonisation
- Pseudomonas elastase cleaves IgG and C1q which prevents initiation of the classical pathway
- C5a peptidase (Strep, Serriatia) cleaves C5a and prevents neutrophil chemotaxis
What does Staphylokinase (Sak) and Streptokinase both do?
They convert plasminogen to plasmin, which cleaves TgG , C3b - creating a capsule around the bacterium so it looks like “self”
What are some ways bacteria recuit or mimic complement regulators?
- C4 binding protein (C$BP) accelerates decay of C3 convertases and is recruited by…
Strep (M protein)
E. coli (OmpA)
Neisseria gonorrhoeae (porin) - Factor H (FH) degrades C3b and accelerates decay of AP C3 cnvertases. It is recruited by Strep (M protein) and Haemophilus influenza
How is LPS used to evade the immune system?
- It can be modified with sialic acid. Factor H will prevent opsonisation of sialic acidcontaining surfaces (because our cells have this) - many strains of Neisseria have this
- Long side chains (O antigen) so phagocytes can’t physically reach receptors (C3b) to target the bacterium. Pseudomonas does this.
What is an example of a bacteria that uses a hyaluronic acid capsule to evade the immune system
Streptococcus pyogenes
What are some ways that bacteria evade destruction in phagocytes?
- Blocking the proton pump (ureC) which prevents acidification.
- Blocking lysosome fusion with the phagosome which arrests phagosome maturation. M. tuberculosis does this.
- Produce a catalase that conversts H2O2 to oxygen and water
- Produce a phenolic glycolipid to prevent attack by ROI. Mycobacterium do this.
- Make a pore in the phagosome for bacterium to escape to cytosol through. Done by cytolysins, e.g. listerolysin
How and why do bacteria invade non-phagocytic cells?
For shelter Uptake induced by bacteria by inducing a reorganisation of the actin cytoskeleton of the host cell Some bacteria inject toxins (effectors) T3SS - Type 3 secretion system E. Coli, Shigella, Salmonella
