microbial pathogenicity and virulence

Question 1

why bother studying infectious disease the mechanisms of pathogenesis?

Answer 1

antibiotics were introduced in the 1950s - before their introduction microbial infections were the leading cause of death worldwide
- in the beginning of the 20th century a better understanding of infections have meant there were better hygiene practices and this meant that infectious diseases started to be reduced but Infectious disease was still a leading cause of death.
- So in the 1950s antibiotics became widely available and they would just seen as a miracle drug as bacterial infections were now treatable
- so over the next few decades microbes weren’t really studied in terms of identifying new antibiotics new treatments.

Question 2

why do microbial infections remain a leading cause of death and concern

Answer 2

• antibiotic/ drug resistance
• emerging and re-emerging infectious diseases
• large outbreaks of food-borne and water-borne infections
• hospital-acquired infections
• microbiota shift diseases
• bioterrorism

Question 3

microbiota shift diseases

Answer 3

something we weren’t aware of until relatively recently is microbiota shift diseases. So we’re now much more aware of the importance of the microbiota in the microbiome, and we now know that shifts and your microbiota can cause diseases

Question 4

emerging and re-emerging infectious diseases

Answer 4

there are 3 classes:
diseases caused by previously unidentified. microbes
- these are microbes that we are only recently aware have entered the human population
- covid-19 classic example of that

diseases known for a longtime but microbial cause only recently identified
- E.g We’ve always known about gastroenteritis being infectious, but it’s only recently that we’ve been able to culture the organism and then show that that’s responsible for the majority of cases of bacterial gastroenteritis.

old diseases that have returned due to conditions favouring their emergence
- this could be that antibiotic resistance or it could be changes in what we’re doing

Question 5

factors associated with increasing incidence of diseases - modern medicine

Answer 5

• Modern medicines as a source of new disease
  
  • opportunistic infections
    - increase in immunocompromised patients
    - nosocomial infections

Question 6

factors associated with increasing incidence of diseases - changing human practices

Answer 6

○ foodborne and waterborne diseases - globalization means we’ve got global distribution, which has an effect
○ and zoonotic infections - So zoonotic infections are transmitted from animals to humans.

Question 7

factors associated with increasing incidence of diseases - rapid change in genetic makeup of microbes

Answer 7

-horizontal Gene transfer that allows movement of large sections of DNA so they can transmit virulence factors, antibiotic resistance genes easily between them
○ but also some organisms hypermutate, rapidly change and so can create new diseases so you might have it under control and then it mutates and then you need to control the new version.

Question 8

septicaemia

Answer 8

Septicemia is where you get an infection within the blood and several organisms are responsible for septicemia.
- group A strep is one of those pathogens

Another organism responsible for septicemia sepsis is meningococcal meningitis

Question 9

colonisation

Answer 9

ability of a microbe to remain at a particular location and multiply there

Question 10

infection

Answer 10

successful colonisation and multiplication by a microbe capable of causing disease

Question 11

disease

Answer 11

a dynamic process involving a sufficient change in the normal function of an organism’s cells or tissues to cause symptoms

Question 12

pathogenicity

Answer 12

a microbes ability to cause disease

Question 13

virulence

Answer 13

• the degree of pathology caused by a microbe

Question 14

pathogenesis

Answer 14

mechanisms a microbe uses to cause the disease state

Question 15

virulence factors

Answer 15

features that contribute to the ability of a microbe to colonise and cause disease

Question 16

pathogen

Answer 16

a pathogen is a microbe capable of causing disease, but not all pathogens have the same ability to cause disease
- you either have true (primary) pathogens or opportunistic (secondary) pathogens

Question 17

true pathogen

Answer 17

true pathogen is likely to cause disease in a healthy host - an infection of someone that’s not been previously immunized against it. So it’s someone meets that organism for the first time it will invariably cause disease.

Question 18

opportunistic pathogens

Answer 18

○ these generally only cause disease in a compromised host.
○ So they’ve got a weakened immune system in some way
○ or it can be that that microbe enters an unusual site in a host
This is usually due to a breach in their immune system

Question 19

how to prove that a particular microorganism causes a disease - robert koch

Answer 19

the person that came up with how To isolate and culture microbes and because of this it led him to come up with Koch’s postulates.
-these are referred to as the four Commandments of infectious disease

Question 20

Kochs postulates

Answer 20

1. the microbe must be associated with symptoms of the disease and be present at the site of infection
2. the microbe must be isolated from disease lesions and grown as a pure culture
3. cultured microbe should reproduce the disease when inoculated into a susceptible healthy host
4. the microbe must be re-isolated from the host used in 3

Question 21

Kochs first postulate

Answer 21

first postulate is that the microbe must be associated with symptoms of the disease or disease lesion and be present at the site of infection or present in the disease lesions, but not in healthy tissues or not in people without the disease.
-one of the problems with this is we now know that lots of diseases are Caused by organisms that are often commensals
- not everybody that has a particular organism on them necessarily gets a disease.

Question 22

Kochs second postulate

Answer 22

○ the second postulate is that the microbe must be isolated from the disease lesions and grown as pure culture
- But as we know now there are loads of microbes We can’t culture

Question 23

kochs 3rd postulate

Answer 23

○ Third postulate is that the microbes should reproduce a disease when inoculated into a susceptible healthy host
- now at the time that Robert Koch produced these postulates they were using human volunteers for these experiments And so this was quite straightforward
- now we would not do that and often animals are used as the host
- a lot of disease is a human specific. And so there’s no good animal model and so it’s very difficult to fulfill this postulate.

Question 24

kochs 4th postulate

Answer 24

○ last one is that the microbe must be re isolated from the host used in three and
you can grow your culture
§ if you managed to fulfill the first three then this is very straightforward
§ and it’s important because what it does show is that it was actually that organism that you introduced that cause the disease
the fact you can re isolate it again means it has gotten their propagated course of disease.

Question 25

kochs proposed 5th postulate

Answer 25

now there’s a proposed fifth postulate that invariably gets evoked.
- this is that knowledge of the microbes should enable effective therapeutic or preventative measures.

Question 26

kochs postualte in gastric ulcers

Answer 26

recent use of Koch’s postulates is gastric ulcers.
- Marshall and Warren fairly recently isolated helicobacter pylori from stomach ulcers and came up with the idea that this organism cause stomach ulcers
- up until then it was always considered that stomach ulcers were due to stress
- stomach ulcers were thought to be pretty much untreatable and we’re a problem then in the 1980s.
- They isolated the bacteria and then they tried to apply Koch’s postulates to show that the microbe was the causative agent of stomach ulcers and that they did actually
use the Koch’s postulates.

Question 27

how did they show that the microbe was the causative agent of ulcers using Kochs postulate

Answer 27

The problem is there’s no animal model for helicobacter Pylor
so to get through these Koch’s postulates Marshall actually drank a live culture of the bacteria and gave him inflammation of the stomach,
- but he’d also worked out the treatment - fifth postulate - and so then so he was able to isolate the bacteria from himself with the lesions in his stomach showing that that organism Infected but then he could treat it with antibiotics and cured himself.
now we know that the disease is treatable and that you can treat stomach ulcers just with antibiotics

Question 28

modern approaches to try and satisfy Koch’s postulates where we’ve had issues.

Answer 28

• the fact we can’t culture all microbes, we can get around this by using for example PCR now
• you can Immunohistochemistry to see antibodies against an organism to see whether it’s present
• antibiotic therapy can be used to eliminate the microbe and cure the disease so that helps you know that the microbe is responsible
• and in a similar way vaccination can be used
• And then another approach is if we think it’s an infectious agent, we can’t identify it, But if you start introducing hygiene disinfection health practices, for example, if that helps to reduce the incidence of the disease it helps demonstrate this is due to an infectious agent

Question 29

how to prove a particular gene or genes from a pathogen contribute to virulence

Answer 29

in 1988 Falkow establish ‘molecular Kochs postulate’
1. identify gene responsible for virulence determinant
2. the gene should only be found in strains of bacteria that cause the disease and not in avirulent bacteria
3. the gene should be isolated by cloning
4. disruption/ knockout of the gene in a virulent bacteria should reduce its virulence
5. introduction of the cloned gene into an avirulent strain should confer virulence
6. the gene should be expressed in the host during an infection

Question 30

molecular virulence traits

Answer 30

virulence factors may include adhesion, invasion, or secretion factors, as well as toxins

genes for these may be passed via horizontal gene transfer mechanism

DNA segments containing cluster of genes involved in pathogenesis are known as pathogenicity islands

Question 31

the infectious disease processes - 1st step

Answer 31

In terms of infectious disease process the first point is transmission of the Infectious agent to the host.
- this isn’t always necessary because sometimes you get infections from endogenous organisms. So organisms that would normally be part of your microbiota and then conditions change that means They can now able to cause an infection

Question 32

infectious disease process following transmission

Answer 32

Once they are at the host they need to gain access to the host for colonization. And that means they must be able to penetrate the normal external defences of the body.
- And that’s also true for endogenous pathogens that something needs to happen that suddenly they can now start to overgrow and colonise
They also need to evade the immune defences for long enough that they can persist and start to multiply
and they also need to be able to obtain nutrients in order to grow and multiply

• these 3 steps are all absolutely in central for establishing an infection, Whereas the transmission isn’t necessarily needed.

Question 33

the infectious disease process - after colonisation

Answer 33

So once they’ve colonised, they’re multiplying -the organism can stay localized at the initial site of colonization.
- And that in many cases is enough to cause devastating disease
- but sometimes they also spread within the body and then the infection become systemic
and also particularly for human specific pathogens, They also need to exit the host to spread to other host

Question 34

the infectious disease process - after spread

Answer 34

disease symptoms
this results from two possibilities.
○ It can be a direct effect of the pathogen on the host. So for example, they might produce a toxin that damages the host
○ or It’s actually the host response to The infection that causes symptoms of disease.
§ So it’s your immune system trying to control the infection that gets out of hand and that’s what causes the disease symptoms.

Question 35

how do microbes reach us - immediate source

Answer 35

• for every infection, there needs to be an immediate source.
  the immediate source can be the habitat from which the organism is transmitted, but it doesn’t necessarily normally survive there, It just needs to be there long enough to cause infection.

Question 36

how do microbes reach us - reservoir

Answer 36

the reservoir is the normal natural habitat for an organism to propagate.
- sometimes the immediate source and the reservoir are the same, but often that’s not the case and distinguishing The two is really important in infection control.
- in most cases there’s a mode of transmission from the source to the host and there’s numerous types of modes of transmission
- and also there need to be a portal of entry
- and for those organisms that spread from that infected individual There’s also a Exit
- so this infection cycle is useful to think about because if you can break any of the links in this cycle, you can start prevent infection.

Question 37

sources of pathogens/ reservoirs

Answer 37

• environment
• zoonotic diseases
• insects/ Arthropods
• another infected human
• host microbiota - normally harmless commensals at certain sites can cause disease when the established balance is upset
• nosocomial infections - infections acquired in hospital

Question 38

how do microbes get in - direct contact

Answer 38

person to person transmission and this is particularly true for human specific pathogens
- and direct contact actually refers to being within a metre of someone
○ so this can include aerosol spread
○ things like talking singing coughing sneezing. All of those are associated with direct transmission

Question 39

how do microbes get in - indirect contact

Answer 39

direct contact the pathogens tend to be less stable in the environment than those that can be transmitted by indirect contact.
○ So indirect contact also includes inhalation of Airborne droplets, but in this case, it’s droplets that have stayed in the environment for a while and It’s not due to being close proximity to someone
○ Indirect contact also includes things like ingestion of contaminated food or water
or Animals insects then you’ve got vehicle-borne or contaminated objects and it’s just a huge list of ways you could get an infection.

Question 40

portals of entry for microbes

Answer 40

-skin
-eyes
- respiratory tract
- GI tract
-urogenital
-blood
-placental