Host-Bacteria Infections Flashcards
Explain how the signs of infection may be caused by the pathogen or by the host’s response
Fine balance between the immune response and pathogens (& immune suppression)
This varies between species and host genetics
Both stress and poor nutrition can offset this balance making it more possible for disease to overwhelm the immune system
Pathogens can also have low or high responses from the immune system
Too low
Abscesses or systemic disease can occur
Too high
The excessive inflammatory response can lead to toxic shock or sepsis
It is also important for the innate immune reponse to recognise
- Own material
- Harmless Environmental material
- Commensals & symbiotic bacteria
If it is unable to do this then it can have detrimental affects such as
-Autoimmune disease
Diabetes
-Allergies Fleas & dust mites -Food incompatibilities milk
Outline the steps in a bacterial infection
Adhesion
Invasion
Intra/extra cellular survival
Subversion of host defense
Replication
Long term survival in host OR Long term survival in host
Outline the role of virulence genes in bacterial pathogens
Molecules expressed by bacteria that allow bacteria to adhere, invade, evade host defense, cause tissue damage, replicate or persist in the host
What is a virulence gene?
Gene encoding a virulence factor
How have virulence genes evolved?
Horizontal transfer of virulence gene (rapid evolution)
- Plasmids
- Transposons
- Phage transduction
Phage’s can package any DNA (chromosomal/plasmid) & transfer to another bacterium
Outline the mechanism pathogens have for interacting with their hosts
Adhesion
Can adhere to:
Cells (respiratory tract epithelium)
Secretory products (e.g. mucus)
Structural components (e.g. Teeth, hoof)
Other bacteria (biofilms such as plaque)
What are the main structures bacteria use for adhesion?
Fimbriae / Pili (proteins)
Most frequent adhesive structure in gram negative bacteria
Long so can attach at a distance
E.g. E coli, Salmonella, Bordetella
Adhesive
Adhesive macromolecules imbedded in membrane
Bacteria that express fimbriae/pili can also express adhesive macromolecule allowing them to bind closer to the host
What are other structures used for in adhesion?
- Capsules (some bacteria have a capsule that prevent adherence)
- Flagellum (main function: motility)
Proteinaceous Fibrils similar to pili
What are the affects of adhesion on the bacteria?
Upregulation of siderophores synthesis
-> Increased ion acquisition
(iron is limited in host)
Inhibition/Stimulation of growth
Induction of more adhesive structures
Synthesis & secretions of proteins required for invasion/host submission
What are the affects of adhesion in the host cell?
Altered morphology
Induction of fluid loss
Induction of cytokine release
Upregulation of intercellular adhesion molecules (integrins etc)
Apoptosis (cell death)
Necrosis
What cells must bacteria avoid/kill to survive within a host?
Innate immune cells (neutrophils & macrophages)
Complement
Defensins
Proteins designed to kill bacteria
Fibrinogen
Trap bacteria
Antibodies
What mechanisms have bacteria evolved to survive a host?
Resistance to host defence
Complement resistance
Avoiding phagocytosis
Protection against recognition antibodies
Active subversion of host defence
-Killing of phagocytic cells
-Changing what host cell does
Toxins Superantigens Bacterial effector proteins injected into host cells
What is complement resistance?
O-antigen polysaccharide chain (LPS) hinder binding of complement proteins
Capsules incorporate sialic acid inhibiting complement activity
What is meant by avoiding phagocytosis?
Capsule neutrophils/ macrophages cannot recognise the bacteria
M Protein (streptococcus equi) actively interferes with phagocytosis
Production of Fc binding proteins to prevent interaction with Fc receptors on phagocytes
Explain what is meant by protection against recognition antigens
Variation of surface antigens so not to be recognised by specific antibodies
How are Toxins used in subversion of host defences?
Most are A-B toxins (two components - binding & entering to the cell / and enzymatic activity that is responsible for toxicity)
E.g. Anthrax
E coli Verotoxin
Membrane disrupting toxins (haemolysis) E.g. Listeria
Bind & enter host cell
-Pore formation
-Receptor mediated endocytosis (process by which cells take in substances from
outside of the cell by engulfing them in a vesicle)
-Enzyme activity is responsible for toxicity
CR: Outline what Anthrax is and how it works
Highly resistant spores that can survive for extensive periods of time
Zoonotic disease - can lead to death rapidly
All cattle carcasses due to unexplained death must be tested for anthrax before being moved
A: Oedema toxin
- Protective antigen which binds
- Oedema factor
B: Lethal Toxin
- Protective antigen which binds
- Lethal factor
stimulates cytokine which overwhelm the body and it goes into shock leading to a fairly quick death
How do superantigens work in the subversion of the host defence?
Stimulation of APC & T cells
Excessive & uncoordinated release of pro-inflammatory cytokines from the host
Toxic Shock Syndrome
How do Bacterial Effector Proteins work in the subversion of the host defence?
Known as Type 3 secretion systems
Some gram negative bacteria injects proteins into host cell
(incl Salmonella, pathogenic E. coli, Bordetella, Yersinia, Shigella etc)
Adhesions allow for close contact between cells and allow for needle to penetrate host
Mimic enzymes or molecules within the cells to interfere with host machinery
Lethal factors
Change non phagocytic cell to be phagocytic (passage)
How is Strangles transmitted?
Transmitted from other horses or inanimate objects
S Equi travels from roof of mouth or nose to lymph nodes in horse head & neck
Colonisation occurs in guttural pouches leading to long term survival after the horse has recovered from strangles
Carriers can shed S Equi without showing clinical signs
Outline how Streptococcus Equi actively avoids host defence
Bacteria prevents phagocytosis:
- Hyaluronase capsule prevents phagocytosis
- Antiphagocytic enzymes
- M proteins
Binding of fibrinogen which mask binding sites on bacteria
Kills neutrophils rapidly
Toxins produced (Streptolysins S) causes cell lysis
Outline the phagocytic process by which bacteria enter host cells
Phagocytosis
Phagocytes are designed to actively take in bacteria
Con: they are also designed to kill bacteria
Manipulate cells to phagocytise but not kill bacteria
Bacteria can:
-Modify vesicle trafficking
Prevent fusion of phagosomes on lysosomes
-Toxins (Listeria - Haemolysin) to break down phagosome membrane (bacteria are
within phagosome)
-To avoid the break down of phagocytes membrane the enzyme is pH activated. It becomes active in low pH phagosome environment
Explain how bacteria exploit host cell cytoskeletal and metabolic pathways
How does bacteria manipulate those host skeleton to move within the cell
Cytoplasm is extremely viscous which inhibits diffusion (flagella cannot be used)
Manipulation of host cytoskeleton
Some bacteria use nucleation & assembly of host actin filaments at one pole of
bacterium
Growing filaments generate a force which assist bacterial movement
Depolarisation factors in cytosol depolymerise actin again - leads to the
activation of the actin tail
How does bacteria manipulate the host skeleton to move between cells?
Spread cell to cell without exposure to extracellular environment
Actin Tails
E.g. Listeria monocytogenes Shigella flexneri Rickettsia rickettsii
During Cell Division
The clumps of bacteria at the spindle poles will be segregated into the two daughter cells when each infected cell divides.
Also allows for vertical spread from mother to offspring
E.g. Wolbachia associates with microtubules
How does bacteria manipulate the host for nutrients?
Poor access to nutrients within cells (even worse inside vacuole)
Cytosolic bacteria
Direct use of host cellular glucose
Inflammation increases glucose uptake by host cells
Promote host autophagy leading to degradation of complex host
macromolecules to release amino acids
Intravacuolar bacteria
Express glucose transporters into vacuolar membrane Manipulate vesicle transport leading to fusion with endocytic vesicles
Outline the pathway of which bacteria receives nutrients
Cellular mechanisms that convert polymeric nutrients into small building blocks and deliver them to vacuolar pathogens are shown on the right
1: degradation of proteins to amino acids by proteasomes;
2: endocytosis and degradation in lysosomes;
3: autophagosome formation and delivery to lysosomes;
4: vesicle trafficking and fusion/luminal exchange with pathogen-containing vacuole.
CR: What is Mycobacterium Bovis?
Survives as an intracellular pathogen
Primary infection is of alveolar macrophages as localised pulmonary lesions
Can be passed by aerosol or contaminated feed
Exists as a Chronic Infection
Build up of granulomas within the airways (demonstrated effective cell mediated
immunity) which trap the bacteria, however, lesions reduce lung capacity.
This also means the bacteria is not killed and can be reactivated due to stress or
underlying conditions which can then develop onto pulmonary and or generalised
TB
If there is ineffective ell mediated immunity then there is active pulmonary tuberculosis which leads to necrosis and erosion of bronchial wall leading to aerosol (& fecal) shedding
Ineffective mediated immunity also leads to generalised tuberculosis where it spreads through a wide range of tissues, shedding through mucus, faeces, urine and milk
Pasteurisation is important eradicates most bacteria preventing spread of TB to
people and preventing food poisoning in fresh cheese
