Structure Flashcards
What are Koch’s postulates?
- Bacterium is present in every case of the disease
- Bacterium must be isolated from the disease and grown in pure culture
- Specific disease must be reproduced from the pure culture in healthy susceptible host
- Bacterium must again be recovered
What is ‘endemic’?
Disease that occurs regularly at low or moderate frequency
Eg. dental caries
What is ‘epidemic’?
Sudden appearance of disease, or increase above endemic level
Eg. diphtheria
What is ‘pandemic’?
Global epidemic
Eg. cholera
How is bacteria spread by direct contact?
- Sexual contact
- Respiratory tract
- Contamination from own flora
- Contact with skin
- Transplacental
- Parturition
How is syphilis spread?
- Sexual contact
2. Transplacental
How is bacteria spread by indirect contact?
- Inanimate objects
- Food
- Water
- Animals
- Soil
What is a point source outbreak?
Outbreak arising from a single origin
What is a continuous source outbreak?
When the source is not eliminated, spread continues
Especially in poor environments
What is a propagated outbreak?
Host-to-host transmission results in ever greater numbers of infections
What is a biofilm?
Complex multicellular community of bacteria
What bacteria is an obligate parasite?
Chlamydia
What is the difference between bacterial and mammalian cell flagellae?
Bacteria - rotates
Mammalian - waves
How is bacterial mRNA?
Polycistronic - colinear genes
Unstable
No 5’ cap or 3’ polyA tail
How are bacterial cells regulated?
Initiation of transcription rather than post-transcriptional modification
What are the four general types of pathogenic bacteria?
- Cocci
- Rods
- Curved rods
- Spiral
What are endospores?
Dormant bacteria that survive in the environment/soil
Give four examples of bacteria that form endospores
- Tetanus (C. tetani)
- Gas gangrene/food poisoning (C. perfringens)
- Botulism (C. botulinum)
- Anthrax (Bacillus antracis)
What is the difference between Gram-positive and Gram-negative bacteria?
Gram-positive have thicker peptidoglycan cell wall that retains the stain
Gram-negative have extra outer lipopolysaccharide membrane that does not retain the stain
Which bacteria do not Gram-stain?
- Mycobacteria (TB) - acid fast due to waxy lipid coat
- Chlamydia - no cell wall
- Mycoplasma - no cell wall
What is the cell wall made of?
Peptidoglycan
Huge macromolecule of alternating sugar molecules N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM)
These are cross-linked by short oligopeptides
How thick is the Gram-positive peptidoglycan wall?
150-500 angstroms
What is the role of the plasma membrane?
- Osmotic barrier
- Site of signal recognition
- Transport of nutrients
- Respiration
What is the periplasm?
Located between the two membranes in Gram-negative bacteria
Contains hydrolytic enzymes and components of transport
What is the outer membrane of Gram-negative bacteria made of?
Lipopolysaccharide (LPS)
Contains porins for to import/export materials
What is the O-antigen on LPS?
Highly variable
Generates different antigens and therefore different serotypes
Important defence against host attack
What is lipid A in LPS?
Endotoxin
Released from dying bacteria
Major PAMP that triggers wide-ranging immune response
What is the bacterial capsule?
Prevents drying
Protects from host defences
Made of polysaccharide
Eg. Haemophilus influenzae
Eg. Streptococcus pneumoniae
How do proteins cross the inner bacterial membrane?
N-terminal secretion signal
Standard secretion (sec) pathway
Give two examples of facultative anaerobes
- Salmonella
2. Staphylococcus
Give two examples of strict anaerobes
- Clostridium
2. Bacteroides
How do strict anaerobes gain energy?
Fermentation
Give two examples of bacteria with flagellae
- H. pylori
2. Vibrio cholera
How does a motile bacterium change direction?
Switch direction of rotation of flagellum to clockwise
Causes tumbling
What is an operon?
Contiguous genes with common promoter
How does the bacterium sense its environment?
Histidine-aspartate phosphorelay (HAP) signalling pathway
Signal transduction system
What is a regulon?
Network of operons
What is quorum sensing?
Detection of a high population density
Secrete small signal molecule and sense its concentration
Switch on virulence genes only at this point
What is the K antigen?
Capsular polysaccharide
How do bacteria cause DNA rearrangements?
Random capture and insertion of DNA elements called insertion sequences
Few hundred base pairs long
Enter DNA by own recombination system
What are transposons?
Larger bits of DNA
Pick up useful genes
Eg. resistance/virulence genes
Can be picked up by main genome or plasmids
What is a pathogenicity island?
Genes required for infection and survival in the host are grouped together in the bacterial genome
Evolved by integration of transposons, plasmids and bacteriophage, and transformed DNA
Have higher GC content than surrounding DNA
Facilitates virulence gene coregulation
What does Salmonella SP-1 do?
Gene determining entry into non-phagocytic cells
What does Salmonella Sp-2 do?
Gene determining survival in macrophages
Give three ways that bacteria acquire DNA
- Transduction
- Transformation
- Conjugation
What is transduction?
Transfer of DNA to bacteria from bacterial viruses, eg. bacteriophage
What is transformation?
Uptake of DNA from dead/lysed bacteria
What is conjugation?
Direct transfer requiring contact between two bacteria
How does the skin protect against bacteria?
- Dry, acidic, cool, high salt so limits growth
2. Sloughing cells removes bacteria
How do the mucous membranes protect against bacteria?
- Mucin layer traps bacteria
- Cilia waft up mucus out of respiratory tract to be swallowed
- Tight junctions limits paracellular invasion
- Lysozyme in tears splits peptidoglycan
How does the body reduce iron available to bacteria?
Sequestration by lactoferrin and transferrin
How does resident microflora protect against infection?
Inhibits colonisation by occupancy and competition for space and nutrients, too high levels of waste,
Which complement pathway is activated by bacteria?
Alternative
How do bacteria attach to host cells?
Cell surface adhesins bind to carbohydrate and glycolipid receptors on host membrane or extracellular matrix
How are adhesin proteins assembled?
On the tips of long rigid pili
Eg. P-pilus adhesin of UPEC binding to kidney receptor
What do common (type 1) pili bind to?
Bladder cells
What do Pap (P-pili) bind to?
Kidney receptors
How does UPEC persist in bladder cells?
- Superficial epithelial cells undergo exfoliation during infection
- UPEC invades underlying immature epithelial cells
- Persist in quiescent reservoirs and can resurge to cause reinfection
What are pedestals?
EHEC and EPEC use specialised needles to inject proteins into host cell
Including specialised Tir receptor
Binding of bacterial surface intimin to Tir subverts host cell signal transduction and leads to actin polymerisation, forming a pedestal
Bacterium is very tightly adherent to pedestal
Give three bacteria that form biofilms
- Streptococcus mutans - forms plaque on teeth leading to caries
- Staphylococci - colonise catheters
- Pseudomonas aeruginosa - colonise contact lenses leading to conjunctivitis
Where do P. aeruginosa biofilms form?
- Contact lenses
2. Lungs of people with cystic fibrosis
What do P. aeruginosa form in the lungs of people with cystic fibrosis?
Biofilm
Copious production of alginate polysaccharide slime
Protects bacteria in biofilm from host defences and antimicrobials
What are the two mechanisms by which bacteria enter host cells?
- Zipper mechanism
2. Trigger mechanism
What is the zipper mechanism?
Receptor mediated endocytosis
Bacterial invasins mimic eukaryotic ligands
Eg. triggered by Listeria
What is the trigger mechanism?
Subversion by bacterial effector proteins
Delivered directly into cell by needles
Eg. Salmonella
How does Listeria spread?
Escapes from entry vacuole into cytosol
Intracellular movement and replication leads to intercellular spread
Forms a comet tail by actin polymerisation
How does Salmonella spread?
Stays in entry vacuole and replicates
Survives in macrophages
Spread locally and throughout body by host defence system
Give two diseases caused by Chlamydia
- Trachoma
2. Non-gonococcal urethritis
What is trachoma?
Most common cause of infectious blindness in developing world
What is non-gonococcal urethritis?
STI
Often asymptomatic - many silent carriers
Can cause acute prostatitis, pelvic inflammatory disease and infertility
How big is the Chlamydia genome?
Approx 900 genes
What are the two stages of Chlamydia development?
- Infectious elementary body (EB)
2. Reticulate body
What does the infectious elementary body of Chlamydia do?
Low metabolic activity and cannot replicate
- Attaches to host membrane and induces uptake in endosome
- Chlamydia effector Tarp injected by needle rearranges host actin cytoskeleton
- Differentiates into RB in endosome
What does the reticulate body of Chlamydia do?
Metabolically active and replicates
- Produces both RBs and EBs
What causes damage in Chlamydia infection?
Host cell lysis
Inflammation triggered by chlamydial LPS
What enzymes break down connective tissue?
- Collagenase
2. Hyaluronidase
What does staphylokinase do?
Breaks down blood clots
What does coagulase do?
Induces fibrin clot formation
What does DNAse do?
Breaks down DNA in pus
What does pyogenic mean?
Pus-making
Eg. Streptococci and Staphylococci
What are siderophores?
Iron-binding proteins secreted by pathogens to bind iron and reimport it into the bacterial cell
What is pyoverdin?
Siderophore
Secreted by P. aeruginosa
Green fluorescent
How do bacteria protect themselves from stomach acid?
- Pump H+ out of their cells
2. Secrete urease to produce NH3 to neutralise pH
How do bacteria prevent uptake by macrophages?
- Paralyse macrophage by subverting its functions
- Inhibit chemotaxis
- Resist phagocytosis by shielding with antiphagocytic capsules
- Kill macrophages with secreted cytolysins
How do bacteria paralyse macrophages?
Disrupt intracellular trafficking and signal transduction by injecting anti-phagocytic proteins via needle
What is YopT?
Yersinia (plague) effector
Protease that targets small GTPases to disrupt cytoskeleton
Paralyses macrophages
What is YopP?
Yersinia effector
Acetyl transferase that inhibits signalling to initiate apoptosis
Paralyses macrophages
How do bacteria inhibit chemotaxis?
Cleave complement C5a with C5a peptidase
How do capsules help avoid phagocytosis?
- Non-immunogenic polysaccharide - sialic acid
2. Lack affinity for complement factor B - C3b not formed
What are cytolysins?
Pore-forming toxins
Disrupt cell functions
Cause apoptosis
Destroy cell membrane integrity - enzymatic destruction of membrane phospholipids
What produces cytolysins?
- Gram positive Strep. pyogenes (streptolysin O and S)
- Pneumococcus (pneumolysin)
- Pertussis
How do bacteria survive inside the macrophage?
Interfere with phagosome maturation
Inhibit phagosome-lysosome fusion
Resist oxidative burst
How does Legionella survive?
Multiplies in alveolar macrophages
Prevents oxidative burst by modifying host phagosome with bacterial proteins that block lysosome fusion
Stimulates cytokine release and intense inflammatory response
How does Legionella survive in air conditioning?
Facultative intracellular parasite of amoebae
How do bacteria resist complement?
LPS O-antigen and capsule hinder access to bacterial cell wall, preventing formation of membrane attack complex
How do bacteria evade recognition by antibodies?
- Mimic host
- Shut off or change expression of surface antigens by phase variation
- Antigenic variation
How do bacteria inactivate antibodies?
- Secretory IgA is cleaved by specific proteases of mucosal pathogens
- Bind Fc region of antibody to prevent opsonisation
Give four bacteria that cleave secretory IgA
- Streptococcus pneumoniae
- Haemophilus influenzae
- Neisseria gonorrhoea
- Neisseria meningitidis
What are the two groups of bacterial exotoxins?
- Cytolysins
2. Intracellular enzymatic toxins
Give an example of a cytolysin
- Phospholipase - C. perfringens α-toxin
- Pneumolysin
- Haemolysin
- Helicobacter VacA
What is the advantage of cytolysins?
- Disable immune cells
- Assist tissue damage
- Bacterial spread
What do cytolysins do at low concentrations?
Subvert the host cell signal transduction
Cause release of leukotrienes and histamine
Trigger apoptosis
What do enzymatic intracellular toxins do?
Poison host cells by specific catalytic activity
What is the structure of enzymatic intracellular toxins?
Intracellularly active (A) component
Receptor binding (B) component
Can be single polypeptides cleaved to active fragments or multimeric
Give examples of single polypeptide enzymatic intracellular toxins
- Diphtheria toxin
- Tetanus toxin
- Botulinum toxin
Give examples of multimeric polypeptide enzymatic intracellular toxins
- Anthrax
- Pertussis
- Cholera
How do intracellular toxins enter cells?
- Receptor-mediated endocytosis
2. Retrograde transport
What do ADP-ribosylating enzymes do?
ADP-ribosylate regulators of adenylyl cyclase
Leads to disturbance of cAMP levels, signalling and ion balance
Give three examples of ADP-ribosylating enzymes
- Cholera toxin
- Pertussis toxin
- E. coli enterotoxin (labile toxin LT)
What does diphtheria toxin do?
ADP-ribosylates elongation factor 2
Blocks protein synthesis
What does pertussis toxin do?
- ADP-ribosylates regulators of adenylate cyclase
2. Produces its own adenylate cyclase, which mimics host AC
What does anthrax toxin do?
Produces adenylate cyclase, mimicking host AC
Disturbs cAMP levels
What does Shiga toxin do?
Glycosidase that depurinates 28S rRNA
Blocks protein synthesis
What does C. difficile toxin do?
Glucosylates small GTPases involved in signal transduction
Disrupts actin cytoskeleton and tight junctions
What do cytolethal distending toxins do?
Cleave DNA
What is cytotoxic necrotising factor?
Deamidase that targets host cell GTPases
Disrupts cell signalling to reorganise acting cytoskeleton
Give two examples of neurotoxin
- Tetanus toxin
2. Botulinum toxin
On which nerves does tetanus toxin act?
Inhibitory interneurons
Blocks transmitter release
On which nerves does botulinum toxin act?
Peripheral nerves
A chain cleaves synaptobrevin
Blocks ACh release
What paralysis does tetanus cause?
Spastic paralysis
Uncontrollable muscle contraction
What paralysis does botulism cause?
Flaccid paralysis
What are the advantages of enzymatic toxins?
- Aid colonisation
- Aid transmission
- Aid dissemination by killing host and providing anaerobic environment for growth (tetanus and botulism)
What are superantigens?
Bind outside normal antigen binding pocket on TCR
Bridge weakly interacting MHC II and TCR
Activates useless T cells
Can cause cytokine storm
What is toxic shock syndrome?
Toxic shock syndrome toxin produced by S. aureus growing in highly absorbent tampons
Causes shock, multi-organ failure, cytokine storm
How does LPS cause acute inflammation?
- Released from dead bacteria
- Bound by LPS-binding protein
- Delivered to macrophage receptors (CD13 and TLR4)
- Triggers activation of cytokine genes
What causes septicaemia?
Lipid A endotoxin overload as large numbers of bacteria die
Triggers strong innate immune response
What bacterial components trigger acute inflammation?
- LPS
- Lipid A
- Peptidoglycan
- Flagellin
What causes meningitis?
- Bacteraemia
- Endothelial cell damage
- Bacteria crosses blood brain barrier
- Inflammation of meninges caused by lipid A
What bacteria can cause meningitis?
- Neisseria meningitidis
- Haemophilus influenzae type B
- Streptococcus pneumoniae
- E. coli (neonatal meningitis)
What is streptococcal glomerulonephritis?
Type III hypersensitivity reaction following lodging of immune complexes in the kidney
