Host-Bacteria Infections

Question 1

Explain how the signs of infection may be caused by the pathogen or by the host’s response

Answer 1

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

Question 2

Outline the steps in a bacterial infection

Answer 2

Adhesion

Invasion
Intra/extra cellular survival

Subversion of host defense

Replication

Long term survival in host OR Long term survival in host

Question 3

Outline the role of virulence genes in bacterial pathogens

Answer 3

Molecules expressed by bacteria that allow bacteria to adhere, invade, evade host defense, cause tissue damage, replicate or persist in the host

Question 4

What is a virulence gene?

Answer 4

Gene encoding a virulence factor

Question 5

How have virulence genes evolved?

Answer 5

Horizontal transfer of virulence gene (rapid evolution)
- Plasmids
- Transposons
- Phage transduction
Phage’s can package any DNA (chromosomal/plasmid) & transfer to another bacterium

Question 6

Outline the mechanism pathogens have for interacting with their hosts

Answer 6

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)

Question 7

What are the main structures bacteria use for adhesion?

Answer 7

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

Question 8

What are other structures used for in adhesion?

Answer 8

• Capsules (some bacteria have a capsule that prevent adherence)
• Flagellum (main function: motility)
  Proteinaceous Fibrils similar to pili

Question 9

What are the affects of adhesion on the bacteria?

Answer 9

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

Question 10

What are the affects of adhesion in the host cell?

Answer 10

Altered morphology

Induction of fluid loss

Induction of cytokine release

Upregulation of intercellular adhesion molecules (integrins etc)

Apoptosis (cell death)
Necrosis

Question 11

What cells must bacteria avoid/kill to survive within a host?

Answer 11

Innate immune cells (neutrophils & macrophages)

Complement

Defensins
Proteins designed to kill bacteria
Fibrinogen
Trap bacteria
Antibodies

Question 12

What mechanisms have bacteria evolved to survive a host?

Answer 12

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

Question 13

What is complement resistance?

Answer 13

O-antigen polysaccharide chain (LPS) hinder binding of complement proteins
Capsules incorporate sialic acid inhibiting complement activity

Question 14

What is meant by avoiding phagocytosis?

Answer 14

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

Question 15

Explain what is meant by protection against recognition antigens

Answer 15

Variation of surface antigens so not to be recognised by specific antibodies

Question 16

How are Toxins used in subversion of host defences?

Answer 16

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

Question 17

CR: Outline what Anthrax is and how it works

Answer 17

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

Question 18

How do superantigens work in the subversion of the host defence?

Answer 18

Stimulation of APC & T cells

Excessive & uncoordinated release of pro-inflammatory cytokines from the host

Toxic Shock Syndrome

Question 19

How do Bacterial Effector Proteins work in the subversion of the host defence?

Answer 19

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)

Question 20

How is Strangles transmitted?

Answer 20

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

Question 21

Outline how Streptococcus Equi actively avoids host defence

Answer 21

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

Question 22

Outline the phagocytic process by which bacteria enter host cells

Answer 22

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

Question 23

Explain how bacteria exploit host cell cytoskeletal and metabolic pathways

Question 24

How does bacteria manipulate those host skeleton to move within the cell

Answer 24

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

Question 25

How does bacteria manipulate the host skeleton to move between cells?

Answer 25

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

Question 26

How does bacteria manipulate the host for nutrients?

Answer 26

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

Question 27

Outline the pathway of which bacteria receives nutrients

Answer 27

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.

Question 28

CR: What is Mycobacterium Bovis?

Answer 28

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