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Questions and Answers
What is the primary characteristic of the microbiota in the human body?
What is the primary characteristic of the microbiota in the human body?
What is the typical ratio of bacteria and archaea to human cells in an average adult?
What is the typical ratio of bacteria and archaea to human cells in an average adult?
Where are the majority of normal flora located in the human body?
Where are the majority of normal flora located in the human body?
What can opportunistic pathogens do when a person is immunocompromised?
What can opportunistic pathogens do when a person is immunocompromised?
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Which of the following describes a relationship where both organisms benefit?
Which of the following describes a relationship where both organisms benefit?
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What is primarily indicated when microorganisms are described as normal flora?
What is primarily indicated when microorganisms are described as normal flora?
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What is a common characteristic of the normal flora found on human body surfaces?
What is a common characteristic of the normal flora found on human body surfaces?
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Which anatomical site in the human body encompasses the largest area inhabited by normal flora?
Which anatomical site in the human body encompasses the largest area inhabited by normal flora?
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What is the primary mechanism by which botulinum toxin affects muscle tissue?
What is the primary mechanism by which botulinum toxin affects muscle tissue?
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Which condition is most commonly associated with Campylobacter jejuni?
Which condition is most commonly associated with Campylobacter jejuni?
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What type of toxins are endotoxins typically found in?
What type of toxins are endotoxins typically found in?
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What effect do superantigen toxins have on the immune system?
What effect do superantigen toxins have on the immune system?
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Which of the following food items can lead to outbreaks of infant botulism?
Which of the following food items can lead to outbreaks of infant botulism?
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What is a notable syndrome that can develop in 1 in 1000 cases of Campylobacter jejuni infections?
What is a notable syndrome that can develop in 1 in 1000 cases of Campylobacter jejuni infections?
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What characteristic differentiates exotoxins from endotoxins?
What characteristic differentiates exotoxins from endotoxins?
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How do superantigens contribute to tissue damage?
How do superantigens contribute to tissue damage?
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What immune response does the body display due to Campylobacter jejuni LPS components?
What immune response does the body display due to Campylobacter jejuni LPS components?
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What is a primary method of transmission for tuberculosis?
What is a primary method of transmission for tuberculosis?
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What critical role does cell-mediated immunity play in tuberculosis?
What critical role does cell-mediated immunity play in tuberculosis?
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What characterizes multidrug-resistant tuberculosis (MDR TB)?
What characterizes multidrug-resistant tuberculosis (MDR TB)?
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Which of the following is NOT a recommended method to prevent the spread of tuberculosis?
Which of the following is NOT a recommended method to prevent the spread of tuberculosis?
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How is the treatment for tuberculosis typically characterized?
How is the treatment for tuberculosis typically characterized?
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What structural feature contributes to the acid-fastness of mycobacteria?
What structural feature contributes to the acid-fastness of mycobacteria?
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Which of the following factors differentiates the upper and lower respiratory tracts in terms of microbial colonization?
Which of the following factors differentiates the upper and lower respiratory tracts in terms of microbial colonization?
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What condition is primarily caused by the accumulation of acid-producing bacteria on teeth?
What condition is primarily caused by the accumulation of acid-producing bacteria on teeth?
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Which bacterium is most commonly associated with the formation of dental caries?
Which bacterium is most commonly associated with the formation of dental caries?
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What is the primary function of the bacteria colonizing the human gastrointestinal tract?
What is the primary function of the bacteria colonizing the human gastrointestinal tract?
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In which part of the digestive system is the microbial population largest?
In which part of the digestive system is the microbial population largest?
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What is a major factor contributing to the formation of dental plaque?
What is a major factor contributing to the formation of dental plaque?
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Which of the following best describes anaerobic bacterial species in the oral cavity?
Which of the following best describes anaerobic bacterial species in the oral cavity?
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What role do mucous membranes play in bacterial infection risk?
What role do mucous membranes play in bacterial infection risk?
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How do bacteria influence the human body beyond digestion?
How do bacteria influence the human body beyond digestion?
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What happens to microbes when they pass quickly through the stomach?
What happens to microbes when they pass quickly through the stomach?
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What is dental plaque primarily composed of?
What is dental plaque primarily composed of?
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Which process eliminates microbes from the large intestine?
Which process eliminates microbes from the large intestine?
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What is the primary source of microorganisms in the oral cavity after birth?
What is the primary source of microorganisms in the oral cavity after birth?
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Which of the following statements about sugar and bacteria is accurate?
Which of the following statements about sugar and bacteria is accurate?
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How does the body counteract the microbial population within the large intestine?
How does the body counteract the microbial population within the large intestine?
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What is the primary role of virulence factors in pathogens?
What is the primary role of virulence factors in pathogens?
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What does LD50 represent in the context of virulence?
What does LD50 represent in the context of virulence?
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Which enzyme breaks down hyaluronic acid and aids bacterial invasion?
Which enzyme breaks down hyaluronic acid and aids bacterial invasion?
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How does coagulase function in terms of pathogen protection?
How does coagulase function in terms of pathogen protection?
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Which toxin directly damages the integrity of host cell membranes?
Which toxin directly damages the integrity of host cell membranes?
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What is the function of siderophores in bacterial pathogens?
What is the function of siderophores in bacterial pathogens?
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Which characteristic differentiates highly virulent pathogens from less virulent ones in terms of LD50?
Which characteristic differentiates highly virulent pathogens from less virulent ones in terms of LD50?
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How does the Diphtheria toxin impact host cells?
How does the Diphtheria toxin impact host cells?
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Which of the following best describes the role of fimbriae in bacterial pathogens?
Which of the following best describes the role of fimbriae in bacterial pathogens?
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Which type of exotoxin is characterized by its ability to stimulate excessive immune responses?
Which type of exotoxin is characterized by its ability to stimulate excessive immune responses?
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What component of the Gram-negative cell wall is considered a virulence factor?
What component of the Gram-negative cell wall is considered a virulence factor?
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What process allows bacteria to acquire virulence factors via genetic exchange?
What process allows bacteria to acquire virulence factors via genetic exchange?
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How do hemolysins affect red blood cells?
How do hemolysins affect red blood cells?
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What is a key function of enterotoxins specifically in food-borne pathogens?
What is a key function of enterotoxins specifically in food-borne pathogens?
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What characterizes extensively drug resistant tuberculosis (XDR TB)?
What characterizes extensively drug resistant tuberculosis (XDR TB)?
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Which age groups are more susceptible to infectious diseases?
Which age groups are more susceptible to infectious diseases?
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What is the role of the immune memory in the immune system?
What is the role of the immune memory in the immune system?
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Which factor does NOT contribute to a compromised host's susceptibility to infection?
Which factor does NOT contribute to a compromised host's susceptibility to infection?
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What is the main purpose of vaccination?
What is the main purpose of vaccination?
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What is required for herd immunity to be effective?
What is required for herd immunity to be effective?
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What is a key challenge in creating new flu vaccines each year?
What is a key challenge in creating new flu vaccines each year?
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Which of the following is NOT a component of specific immunity?
Which of the following is NOT a component of specific immunity?
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What condition is associated with a higher risk of TB infection?
What condition is associated with a higher risk of TB infection?
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What is a common misconception about herd immunity?
What is a common misconception about herd immunity?
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Study Notes
Medical Microbiology BS2002 Lecture 9
- Lecture presented by A/Prof Yann Boucher, SCELSE, Public Health, NUS
- Email address: [email protected]
Pippi and Scientific Pedigree
- Carl Woese, just shy of Nobel, Father of Archaea
- Norm Pace, NAS member, Father of 16S
- Ford Doolittle, NAS member, Father of LGT
- Yann Boucher, Dog owner, Father of new Vibrio species,
Meet your Prof
- Images depicting various locations and activities
Medical Microbiology - Human Body Diversity
- Human body is a diverse environment
- Specific niches exist
- Most microbes are benign
- Application of ecological principles is important
- Many interactions between humans and normal microbial flora
- Microbiota: microbes regularly found at a given anatomical site
Normal Flora
- Microorganisms living on body surfaces of healthy individuals
- ~10^14 bacteria and archaea in average adult (about 10^13 human cells)
- Most in the gut (400 m² surface)
- Skin (2 m²)
- Mouth
- Respiratory tract
- Urogenital tract
- Many normal flora are opportunistic pathogens
- Commensalism or mutualism
Mouth
- Microbes adhere to gums and teeth
- Not removed by brushing
- Acid contributes to dental plaque, caries, gingivitis, and periodontal disease
- Oral cavity is colonized by microorganisms from the surrounding environment within hours following birth
Oral Microbes and Bacteria
- Bacteria colonize tooth surfaces by attaching to glycoproteins deposited by saliva
- Extensive growth of oral microbes results in a thick bacterial layer (dental plaque)
- Anaerobic species produce high concentrations of acid that decalcifies tooth enamel (dental caries): Streptococcus mutans
Gastrointestinal Tract
- Stomach: most microbes are killed by acidic conditions
- Some survive if pass through quickly
- Some survive in food particles
- Small intestine: few organisms
- Large intestine: largest microbial population of body (10^13 to 10^14 microbial cells) eliminated by peristalsis, desquamation, and movement of mucus
- Replaced rapidly due to rapid doubling times
- Most microbes are anaerobes
Bacteria Associated with Mucous Membranes
- Mucous membranes are frequent sites of infection due to a favorable environment for bacterial growth
Major Bacteria Present (Table 28.2)
- Data presented in the shown table
Bacteroides
- Colonizes exfoliated host cells, food particles, and sloughed mucus
- Rapidly eliminated if not attached
- Adheres to particles in the gut, not the gut itself
- Degrades complex carbohydrates along with methanogens for energy
Bacteroides and Obesity
- Human gut: has 10-100 trillion bacteria that break down food (sugar polymers)
- Obese people have less Bacteroides and more Firmicutes
- Bacteroides populations increase as obese people lose weight
- Bacteria-free mice infected with microbial population from guts of obese mice become obese
- Microbes determine how many calories can be extracted and absorbed
Why?
- Firmicutes have numerous enzymes that break down "indigestible" carbohydrates.
Innate Resistance to Infection
- Nonspecific barriers prevent colonization of the host by most pathogens
- Lysozyme in tears and other secretions dissolve cell walls
- Normal flora compete with pathogens
- Rapid pH change inhibits microbial growth
- Flushing of urinary tract prevents colonization
- Blood proteins inhibit microbial growth
- Mucus and phagocytes prevent colonization
- Stomach acidity inhibits microbial growth
- Normal flora compete with pathogens
Deaths by Cause, Circa 2017
- Worldwide mortality data from 2017 presented (see chart)
Worldwide Deaths Due to Infectious Diseases, 2002
- Worldwide mortality data from 2002 presented (see chart) and various causative agents are detailed. This data is used to demonstrate the importance of disease data
Transmission Routes
- Person-to-person: airborne, direct contact, sexually transmitted
- Zoonotic and vector-borne
- Soil-borne
- Waterborne
- Foodborne
Terms of Pathogenicity
- Attenuation: the decrease or loss of virulence
- Toxicity: ability of an organism to cause disease through toxin production; toxins can travel to the host's sites
- Invasiveness: ability of pathogen to grow in host tissue inhibiting host function; causes damage without producing toxin.
- Many pathogens use a combination of toxins, invasiveness, and virulence factors to enhance pathogenicity
Pathogenesis
- Pathogens use various strategies to establish virulence
- Exposure to pathogens
- Adherence to skin or mucosa
- Invasion through epithelium
- Colonization and growth
- Produce virulence factors
- Toxicity (local or systemic)
- Invasiveness (original site and distant sites)
- Tissue damage and disease
Adherence of Pathogen
- Pathogen gains access to host tissues and multiplies before damage can be done
- Infectious bacteria and viruses often adhere specifically to epithelial cells
- Interactions between pathogen surfaces and host cell surfaces facilitate adherence
Major Adherence Factors
- Factors such as capsules/slime layers, adherence proteins, lipoteichoic acid, fimbriae (pili) facilitate the attachment of microbial pathogens
Invasion
- Starts at the site of adherence
- May spread throughout the host via the circulatory or lymphatic systems
- Availability of nutrients is important to pathogen growth
- Pathogens may grow locally at site of invasion or throughout the body
Virulence
- Estimated from experiments using LD50 (lethal dose 50): dose of agent that kills 50% of animals in test group
Virulence
- Highly virulent pathogens: little difference in number of cells between LD50 and LD100
- Moderately virulent pathogens may show greater difference in number of cells between LD50 and LD100.
Virulence Factors
- Enzymes enhance virulence by breaking down or altering host tissue for nutrient access
- Hyaluronidase breaks down hyaluronic acid, protecting pathogens from host defense mechanisms
- Coagulase allows bacteria to be coated with fibrin
- Virulence factors can be encoded by bacteriophages, plasmids, and transposons
Virulence Factors: Salmonella
- LPS (Lipopolysaccharide) is found in gram-negative cell walls and is present in food-borne pathogens
- O-specific polysaccharide
- Iron uptake using siderophores
- Virulence plasmid only in pathogenic strains
- Fimbriae for adherence
- Enterotoxin affects the small intestine
Exotoxins
- Proteins released from pathogenic organism as it grows
- Categories include:
- Cytolytic toxins
- AB toxins
- Superantigen toxins
Cytolytic Toxins
- Work by degrading cytoplasmic membrane integrity
- Causing host cell lysis and death
- Hemolysins
Example; Staphylococcal α-toxin
- Makes a pore in cell membranes for cell death by causing leakage of intracellular components
AB Toxins
- Consist of A and B subunits
- Work by binding to host cell receptor (B subunit) and transfer a damaging agent (A subunit) across the cell membrane
Diphtheria Toxin
- Catalyzes ADP-ribosylation of elongation factor 2 (EF-2)
- Prevents transfer of amino acids to growing peptide chain in ribosome
Botulism (Clostridium botulinum)
- Botulinum toxin blocks the release of acetylcholine to muscle tissue resulting in a permanent relaxed state
- The toxins can be from food and cause paralysis and death
Botulism cases (graph)
- Time-series data showing outbreaks, mostly food-borne, and especially infant botulism.
Superantigens
- Stimulate large numbers of immune cells
- Result in extensive inflammation and tissue damage.
- Antigens mediate interaction with over 5% of lymphocyte pool
Endotoxins
- Lipopolysaccharide (LPS) portion of cell wall of certain gram-negative bacteria
- Generally less toxic than exotoxins
Campylobacter jejuni endotoxins
- Food-borne pathogen of poultry
- Most common cause of bacterial gastroenteritis
- 1 in 1,000 people develop Guillain-Barré Syndrome
- Paralytic disorder
C. jejuni LPS components
- Mimic human gangliosides (host sugars) causing immune system to attack own sugars
Airborne Pathogens
- Aerosols are important for person-to-person transmission
- Most pathogens survive poorly in air
- Respiratory infections, Different pathogens
Respiratory Tract Colonization
- Upper and lower respiratory tracts differ in their environments (temperature, air flow, pH).
- This favors different microbes to colonize the respiratory tract
Tuberculosis
- Caused by Mycobacterium tuberculosis
- Hansen's disease (leprosy) caused by Mycobacterium leprae
- Acid-fast because of the waxy mycolic acid content of their cell walls.
Tuberculosis (Incidence and Transmission)
- Worldwide infectious disease of humans
- Incidence is increasing.
- Transmitted by airborne droplets
- Cell-mediated immunity plays critical role
Tuberculosis (Treatment)
- Prevent by hospitalization of patients, face masks of healthcare workers
- Treatment usually requires a nine-month regimen of isoniazid or rifampin to affect mycolic acid in mycobacteria
- Direct observed therapy is popular to assure compliance and reduce risk
Tuberculosis (MDR and XDR)
- Multidrug-resistant (MDR-TB): resistant to isoniazid and rifampin
- Extensively drug-resistant (XDR-TB): MDR-TB resistant to isoniazid, rifampin, fluoroquinolones, and injectable drugs
Risk Factors of Infection
- Compromised Host: one or more resistance mechanisms are inactive
- Age: factor for determining susceptibility to infectious diseases
- Stress: predisposes healthy individuals
- Diet and lifestyle choices
- Genetic Conditions can compromise a host
Specific Immunity
- Complex, multi-pathway systems; innate immunity (phagocytes), T-cell immunity, and antibody-mediated immunity
- Immune system recognizes organism, person becomes immune, resulting in immune memory
The Immune System
- Complex and diverse to cover
Immunization
- Inoculation with attenuated or killed pathogens or chemically modified exotoxin-vaccination
- Immune system recognizes specific antigens - may mutate
- Why we need new flu vaccine each year: more likely with viral than bacterial diseases
Herd Immunity
- In a context of vaccines, it protects vulnerable individuals that cannot be vaccinated; blocking transmission
- In a context of illness, a sufficient number of population is immunized
Disease Eradication (Polio and Measles)
- Polio and measles need to be eradicated in populations with vaccination, but vaccination campaigns may be compromised.
Reported Cases (Measles)
- Data plotted in time series to show reported cases of measles.
Reported Cases (Polio)
- Data provides a graph showing the prevalence of polio cases.
Polio Virus in Wastewater
- Discovery extending virus's presence in NYC
Additional Information (Table 33.9)
- Table of factors encoded by bacteriophages, plasmids, and transposons
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