Medical Microbiology
Lecture 1 – Introduction to Bacteriology
Microbiome → bacteria/microorganisms in the gut
500-1000 different species in and on our body (skin and gut)
Microbiome as a source of health
➔ Nutrition and metabolism of food
o Breakdown of indigestible polysaccharides
o Production of vitamins B and K
➔ Maturation and instruction of immune system
o Respond to harmful agents, but not to food for example
➔ Colonization resistance → protection against invaders
o Protection from infiltration by harmful microorganisms by competing for nutrients or spot
- Potential disease-causing bacteria among healthy microbiome → risk of infection
Commensalism → presence of microorganisms multiplying in host without damage and reaction from host
Infection → presence (invasion) of microorganisms multiplying in host, with damage to and reaction of host
Opportunistic pathogens commonly present in healthy microbiome
➔ Many pathogens typically colonize skin or mucosal surfaces of healthy individuals without producing
symptoms → because our body is equipped with very effective immune defense mechanisms that kills
any invading bacterium in seconds/minutes
o Occurrence of acute infections → failure of the immune system to fulfill its defense function
o Understanding molecular mechanisms of infections provides insights into host immunity but
also unlocks opportunities for therapies that take host-pathogen interaction into account
- For example → Neisseria meningitidis, Streptococcus pneumoniae, Staphylococcus aureus, group A
Streptococcus
Pathogen → microorganism able to cause disease
Pathogenicity → ability to cause disease in a host organism
Virulence → the degree of pathogenicity of the microbe
Virulence factor → microbial component that contributes to disease-causing ability
Carrier → host that harbors potential pathogen without disease
Relationship between host and pathogen is dynamic since each modifies activities and functions of the other
➔ The outcome of such relationship depends on the virulence of the pathogen and the relative degree of
resistance or susceptibility of the host, due mainly to the effectiveness of the host defense mechanisms
Staphylococcus aureus, most prevalent pathogen of humans, may cause up to one third of all bacterial diseases
ranging from boils and pimples to food poisoning, to septicemia and toxic shock
- Staphylococcal scalded skin syndrome (SSSS) → red blistering skin looking like a burn or scald
o Caused by an upper respiratory infection in children
o Caused by abscesses or septic arthritis in adults
- Food poisoning → nausea, vomiting, and diarrhea
o Caused by ingestion of contaminated food, entry via the gastrointestinal tracts
➔ About 15-40% of healthy humans are carriers of Staphylococcus aureus → can naturally be in the nasal
throat area, ears
➔ Staph aureus is a so-called opportunistic pathogen, when it sees a chance, it will cause infection. The
bacteria need a kind of "entrance" (= port d'entrance) to penetrate the skin or mucosa
,Course of infection is determined by
1. Route of contamination and invasion of the host
2. Properties of the microorganism → pathogenicity of pathogen is due to virulence factors of pathogen
3. Properties of the host
o Child, adult, elderly
o Healthy or reduced resistance
o Vaccination
Pathogenicity
- Invasiveness → ability to invade tissues
o Colonization and bypass of host defense
- Toxigenesis → ability to produce toxins (virulence factors)
o Exotoxins (released from cells) and endotoxins (cell-associated)
Virulence factors
- Adhesins, invasins, capsule, toxins, enzymes, pili
➔ SSSS → exfoliative toxins A and B bind to a molecule within the desmosome and break it up
o Toxins come from the bloodstream
➔ Food poisoning → enterotoxin A
Virulence factors of S. aureus
- Toxins:
o Cytolytic toxins → tissue destruction/abscess formation
o Enterotoxins (A-E) → toxicity (30-50% of the strains)
o Exfoliative toxin → blistering: loss of desmosomes
- Enzymes
o Coagulase → conversion fibrinogen to fibrine
o Hyaluronidase, lipase, fibrinolysis → distribution in tissues
o Catalase → protection against oxygen radicals
Genus Staphylococcus
- More than 30 species
- Commensals, but opportunistic pathogens
- 3 species are most important humane pathogens
▪ S. aureus
▪ S. epidermis
▪ S. saprophyticus
Disease with a similar clinical presentation can be
caused by different pathogens
Neisseria meningitidis
- Gram-negative diplococcus
- Humans are the only natural host
Infection and transmission → transfer of microorganisms from one place to another; possible multiplication,
possible damage, possible reaction of the host
Zoonosis → transmission of microorganisms through contact with animals
,Lecture 2 – Diagnostics of bacterial infections
Detection of bacterial etiology
- Detection of agents → microscopy, culture, nucleic acid detection, antigen detection
- Detection of immunoglobulins against agents → serology
Microscopy
- Gram negative and positive → dye is not washed out in Gram positive bacteria
- Ziehl Neelsen → zuurvaste rods (staven), mycobacteria (bacteria of tuberculosis)
- Methylene blue
Media (solid or liquid)
- Selective/non-selective
Incubation → environment,
duration
Material → sterile/non-sterile
Media, environment and duration → depending on clinical picture and material
Review → selective media and antibiotics to detect the pathogen
Identification of bacteria
- Biochemical → bonte rij, Vitek, Phoenix
- MALDI-TOF MS → automatic protein mass distribution analysis
- Sequence analysis
Resistance against antibiotics
- Microdilution with MIC (minimal inhibitory concentration)
Nucleic acid detection
- When bacteria are not/hardly growing
▪ Mycobacteria
▪ Mycoplasm
▪ Chlamydia
▪ Legionella
▪ Coxiella
Serology
- Detection of specific antibodies against bacteria
o Bordetella pertussis/parapertussis
o Brucella
- Detection of antigens
o Helicobacter
o Legionella
VOC → volatile organic components
➔ organic chemicals that have a high vapor
pressure at room temperature. High vapor
pressure correlates with a low boiling point,
which relates to the number of the sample's
molecules in the surrounding air, a trait known
as volatility. VOCs are responsible for odor of
scents
, Lecture 3 & 4 – Invasive meningococcal disease: Epidemiology and Vaccines
Neisseria meningitidis → “meningococcus”
- Gram-negative diplococcus
- Natural habitat → the human nasopharynx, 5-30% of
population colonized
➔ Only in humans, a lot of carriers among us
Meningococcal carriage prevalence by age → around 19 years of age
Risk factors for meningococcal carriage
- Active and passive smoking
- Kissing
- Crowds
- Frequent bar/disco visits
➔ Carriage decreased in 15 years of time
o Because of changes in risk factors for meningococcal carriage
Invasive meningococcal disease (IMD)
- 0.01% of colonized hosts invasive disease
- Septicemia and/or meningitis
1. Colonization
2. Invasion of epithelium
3. Invasion of blood
4. Disseminations: CSF
IMD
- Meningococcemia → meningococci in
bloodstream
o Sepsis
o Petechial rash → pinpoint, round
spots in skin as result from bleeding
o Disseminated intravascular
coagulation (DIC) → abnormal blood
clotting
▪ Ischemic tissue damage
▪ Purpura fulminans
- Meningitis → inflammation of the protective membranes covering the brain and spinal cord
IMD across Europe → rare but devastating
- 30 EU countries in 2017 → 3221 cases of IMD
o Incidence → 0.45 – 1.33 per 100.000
o Case fatality rate = 9.7%
Incidence of IMD → age distribution and circulation
- Age of the most prevalent carriers (adolescents), but also children
o Spread is mainly caused from the adolescent carrier group
IMD worldwide
- 1.2 million cases of IMD with 135.000 deaths worldwide yearly
o Incidence ranges strongly per region from high (>10/100,000) to low incidence (<2/100,000)
o Mortality rate → 10%-15%
o Morbidity rate → ~30%
- Morbidity in IMD survivors → limb loss, cognitive deficits, hearing loss, seizure disorders
Lecture 1 – Introduction to Bacteriology
Microbiome → bacteria/microorganisms in the gut
500-1000 different species in and on our body (skin and gut)
Microbiome as a source of health
➔ Nutrition and metabolism of food
o Breakdown of indigestible polysaccharides
o Production of vitamins B and K
➔ Maturation and instruction of immune system
o Respond to harmful agents, but not to food for example
➔ Colonization resistance → protection against invaders
o Protection from infiltration by harmful microorganisms by competing for nutrients or spot
- Potential disease-causing bacteria among healthy microbiome → risk of infection
Commensalism → presence of microorganisms multiplying in host without damage and reaction from host
Infection → presence (invasion) of microorganisms multiplying in host, with damage to and reaction of host
Opportunistic pathogens commonly present in healthy microbiome
➔ Many pathogens typically colonize skin or mucosal surfaces of healthy individuals without producing
symptoms → because our body is equipped with very effective immune defense mechanisms that kills
any invading bacterium in seconds/minutes
o Occurrence of acute infections → failure of the immune system to fulfill its defense function
o Understanding molecular mechanisms of infections provides insights into host immunity but
also unlocks opportunities for therapies that take host-pathogen interaction into account
- For example → Neisseria meningitidis, Streptococcus pneumoniae, Staphylococcus aureus, group A
Streptococcus
Pathogen → microorganism able to cause disease
Pathogenicity → ability to cause disease in a host organism
Virulence → the degree of pathogenicity of the microbe
Virulence factor → microbial component that contributes to disease-causing ability
Carrier → host that harbors potential pathogen without disease
Relationship between host and pathogen is dynamic since each modifies activities and functions of the other
➔ The outcome of such relationship depends on the virulence of the pathogen and the relative degree of
resistance or susceptibility of the host, due mainly to the effectiveness of the host defense mechanisms
Staphylococcus aureus, most prevalent pathogen of humans, may cause up to one third of all bacterial diseases
ranging from boils and pimples to food poisoning, to septicemia and toxic shock
- Staphylococcal scalded skin syndrome (SSSS) → red blistering skin looking like a burn or scald
o Caused by an upper respiratory infection in children
o Caused by abscesses or septic arthritis in adults
- Food poisoning → nausea, vomiting, and diarrhea
o Caused by ingestion of contaminated food, entry via the gastrointestinal tracts
➔ About 15-40% of healthy humans are carriers of Staphylococcus aureus → can naturally be in the nasal
throat area, ears
➔ Staph aureus is a so-called opportunistic pathogen, when it sees a chance, it will cause infection. The
bacteria need a kind of "entrance" (= port d'entrance) to penetrate the skin or mucosa
,Course of infection is determined by
1. Route of contamination and invasion of the host
2. Properties of the microorganism → pathogenicity of pathogen is due to virulence factors of pathogen
3. Properties of the host
o Child, adult, elderly
o Healthy or reduced resistance
o Vaccination
Pathogenicity
- Invasiveness → ability to invade tissues
o Colonization and bypass of host defense
- Toxigenesis → ability to produce toxins (virulence factors)
o Exotoxins (released from cells) and endotoxins (cell-associated)
Virulence factors
- Adhesins, invasins, capsule, toxins, enzymes, pili
➔ SSSS → exfoliative toxins A and B bind to a molecule within the desmosome and break it up
o Toxins come from the bloodstream
➔ Food poisoning → enterotoxin A
Virulence factors of S. aureus
- Toxins:
o Cytolytic toxins → tissue destruction/abscess formation
o Enterotoxins (A-E) → toxicity (30-50% of the strains)
o Exfoliative toxin → blistering: loss of desmosomes
- Enzymes
o Coagulase → conversion fibrinogen to fibrine
o Hyaluronidase, lipase, fibrinolysis → distribution in tissues
o Catalase → protection against oxygen radicals
Genus Staphylococcus
- More than 30 species
- Commensals, but opportunistic pathogens
- 3 species are most important humane pathogens
▪ S. aureus
▪ S. epidermis
▪ S. saprophyticus
Disease with a similar clinical presentation can be
caused by different pathogens
Neisseria meningitidis
- Gram-negative diplococcus
- Humans are the only natural host
Infection and transmission → transfer of microorganisms from one place to another; possible multiplication,
possible damage, possible reaction of the host
Zoonosis → transmission of microorganisms through contact with animals
,Lecture 2 – Diagnostics of bacterial infections
Detection of bacterial etiology
- Detection of agents → microscopy, culture, nucleic acid detection, antigen detection
- Detection of immunoglobulins against agents → serology
Microscopy
- Gram negative and positive → dye is not washed out in Gram positive bacteria
- Ziehl Neelsen → zuurvaste rods (staven), mycobacteria (bacteria of tuberculosis)
- Methylene blue
Media (solid or liquid)
- Selective/non-selective
Incubation → environment,
duration
Material → sterile/non-sterile
Media, environment and duration → depending on clinical picture and material
Review → selective media and antibiotics to detect the pathogen
Identification of bacteria
- Biochemical → bonte rij, Vitek, Phoenix
- MALDI-TOF MS → automatic protein mass distribution analysis
- Sequence analysis
Resistance against antibiotics
- Microdilution with MIC (minimal inhibitory concentration)
Nucleic acid detection
- When bacteria are not/hardly growing
▪ Mycobacteria
▪ Mycoplasm
▪ Chlamydia
▪ Legionella
▪ Coxiella
Serology
- Detection of specific antibodies against bacteria
o Bordetella pertussis/parapertussis
o Brucella
- Detection of antigens
o Helicobacter
o Legionella
VOC → volatile organic components
➔ organic chemicals that have a high vapor
pressure at room temperature. High vapor
pressure correlates with a low boiling point,
which relates to the number of the sample's
molecules in the surrounding air, a trait known
as volatility. VOCs are responsible for odor of
scents
, Lecture 3 & 4 – Invasive meningococcal disease: Epidemiology and Vaccines
Neisseria meningitidis → “meningococcus”
- Gram-negative diplococcus
- Natural habitat → the human nasopharynx, 5-30% of
population colonized
➔ Only in humans, a lot of carriers among us
Meningococcal carriage prevalence by age → around 19 years of age
Risk factors for meningococcal carriage
- Active and passive smoking
- Kissing
- Crowds
- Frequent bar/disco visits
➔ Carriage decreased in 15 years of time
o Because of changes in risk factors for meningococcal carriage
Invasive meningococcal disease (IMD)
- 0.01% of colonized hosts invasive disease
- Septicemia and/or meningitis
1. Colonization
2. Invasion of epithelium
3. Invasion of blood
4. Disseminations: CSF
IMD
- Meningococcemia → meningococci in
bloodstream
o Sepsis
o Petechial rash → pinpoint, round
spots in skin as result from bleeding
o Disseminated intravascular
coagulation (DIC) → abnormal blood
clotting
▪ Ischemic tissue damage
▪ Purpura fulminans
- Meningitis → inflammation of the protective membranes covering the brain and spinal cord
IMD across Europe → rare but devastating
- 30 EU countries in 2017 → 3221 cases of IMD
o Incidence → 0.45 – 1.33 per 100.000
o Case fatality rate = 9.7%
Incidence of IMD → age distribution and circulation
- Age of the most prevalent carriers (adolescents), but also children
o Spread is mainly caused from the adolescent carrier group
IMD worldwide
- 1.2 million cases of IMD with 135.000 deaths worldwide yearly
o Incidence ranges strongly per region from high (>10/100,000) to low incidence (<2/100,000)
o Mortality rate → 10%-15%
o Morbidity rate → ~30%
- Morbidity in IMD survivors → limb loss, cognitive deficits, hearing loss, seizure disorders
