Welcome to Dr. Kate Brilakis' Learning Portal

                               toxins
  poisonous substances that many bacteria produce

 which can damage cells and lead to severe infections. 
toxins are classified by:
1. their structure
2. their mechanics of infection
3. their target tissue

Exotoxins: released by living bacteria 
Endotoxins: released as bacteria die and break up
Enterotoxins: target the gut
Cytotoxins: damage tissues causing inflammation
Neurotoxins: affect the nervous system

        infectious dose 50 (ID50)
= how many of the pathogens must be present in order to infect 50% of exposed susceptible hosts.   

        lethal dose 50 (LD50)
= amount of toxin needed to kill 50% if affected hbosts who are not treated. 

​                                         Virulence factors include:
 1. adhesins: help pathogens attach to host cells (ex: fimbriae in bacteria) 
 2. invasion factors: help pathogens enter host cells 
 3. toxins: damage host cells or tissues (ex: exotoxins/endotoxins) 
 4. capsules: protect pathogens from the host's immune system 
 5. spike proteins: help entry into host cells 
 6. immune evasion factors: help pathogens evade the host's immune response 

 virulence

 Dysbiosis
is an imbalance in the gut microbiota.
it's been linked to mood/mental health disorders due to its negative impact on serotonin levels

  let's look at
   bacterial             toxins

    Virulence           Factors

 are molecules or structures used by a pathogen to infect and damage a host and overcome host defenses

Serotonin
 your gut microbiota produces over 90% of the body's serotonin. 
Gut bacteria modulate tryptophan supplies needed for serotonin production.
Serotonin produced in the gut influence your brain via your Vagus nerve.
 The Vagus nerve is a communication highway between the gut and the brain. 

Escherichia, Enterococcus, Candida, and Streptococcus ​have been found to produce serotonin in your gut. 

the lower the ID50 for a pathogen,
the more infectious that pathogen is. 
ID50 
is not related to virulence.
ex: adenovirus (causes the common cold) has a low IDA50 but is not very virulent

virulence and the host
​|it's not just about the pathogen...

the host matters too

chapter 10

pathogenicity

the measles virus
 R0 = 12-18
each person with measles, on average, infects 12-18 other people

normal
​gut microbes 

 compare Ro to Rt
Rt = the effective reproduction number (also called Re or just R)

ex:

the incidence of a microbe invading a host does not guarantee it will cause disease

Your gut microbiota (microbiome/gut flora)
​are the microbes that live in your digestive tract.
This microbiota influences our resistance to pathogens, the health of intestinal tissues, the production of important molecules, and emotional health via the gut–brain axis.
Your colon contains the most microbes with between 300 and 1000 different species present, most of them anaerobic bacteria.  99% of your gut bacteria come from about 30 or 40 species.
55% of your poo is bacteria.

gut microbes and your health

other Ro values:
Chickenpox – 10-12
Polio – 10-12
HIV/AIDS – 2-5
SARS – 0.19-1.08
MERS – 0.3-0.8
Common Cold – 2-3
Ebola – 1.56-1.9

                                   host factors are characteristics of the host that influence
                                   its susceptibility or resistance to infection including:

a. 
Immune status: weakened immune systems/immunocompromised individuals                                                  cause hosts to be more susceptible to infection
b. Genetics: specific genes can confer resistance or susceptibility to specific pathogens
c. Age: very young and very old people are often more vulnerable to infections
d. Nutrition: malnutrition weakens immune systems
e. Co-infections: being already sick impairs a host's ability to fight off other pathogens
f. Gut microbiome: the gut microbiome can influence susceptibility to certain
​                                         infections

toxin producing microbes are toxigenic

the gut - brain axis

microbes have a preference for which cells/tissues/organisms they colonize. 

pathogens more easily transmitted from host to host become common in a population

virulence factors are often linked to transmission

the evolution of virulence
​favors transmission

 gut microbes
      normal   v   pathogenic   

pathogenicity vs virulence

R0 =
the reproduction rate
of a pathogen
Ro
 quantifies the contagiousness and transmissibility of pathogens.

                 examples of bacterial toxins:


 Botulinum toxin:
 Clostridium botulinum produces this neurotoxin
 which causes botulism = muscle paralysis. 

 Tetanus toxin:
 Clostridium tetani produces this neurotoxin causes   tetanus = muscle spasms and rigor. 

 Clostridium perfringens toxin:
 Clostridium perfringens produces toxins causing
 gas gangrene = a severe infection that destroys tissue

 Clostridioides difficile toxin:
 Clostridioides difficile produces these toxins causing
 C. diff infection = diarrhea /colitis.

 Diphtheria toxin:
 Corynebacterium diphtheriae produces exotoxin
  which causes respiratory failure. 

 Shiga toxin:
 E coli and Shigella produces this cytotoxin which
 damages red blood cells and causes severe diarrhea   and kidney failure

microbes that are normally not pathogenic may prove to be opportunistic pathogens should the opportunity present itself. 

microbe/host interactions

           the host-microbe
     relationship is complex

bacteria, viruses, fungi, parasites
 interact with hosts in ways that             aren't always negative: 
 1. commensalistic: microbes                                              benefit                                                  without                                                causing harm
2. mutualistic: host and microbes
                           both benefit
3. parasitic: microbes harm the
                       host

virulence and transmission

pathogenic
gut microbes

Dysbiosis

Dysbiosis and antibiotics

threshold exposure

Understanding how the gut microbiota, serotonin, and the brain-gut axis is critical as we developing new ways to treat mood disorders. Probiotics designed to improve the gut microbiota may be a useful therapy aimed at improving serotonin levels. 
and addressing related health issues.