Lecture Review
Chapter 21
1. [21-01] Compare the properties of bacterial genera Staphylococcus and Streptococcus Name principal species that are human pathogens and diseases they cause – Lecture 9, Slides 5, 6 –
Similarities: Both genera belong to phylum Firmicutes that includes Gram-positive non-motile cocci with low GC content that do NOT form endospores. Both genera include some species that can produce exotoxins and are human pathogens.
Differences: Genus Staphylococcus includes salt-tolerant, catalase-positive facultative anaerobic cocci growing in clusters. Streptococci are part of human normal flora. Principal human pathogen is Staphylococcus aureus, which is also a part of human normal flora. Strains of S. aureus can cause in humans wide variety of infections, from boils to scalded skin syndrome. Genus Streptococcus includes salt-sensitive, catalase-negative aerotolerant cocci that are growing in chains. Streptococci are not part of human flora, but they are often carried asymptomatically. Principal human pathogen is Streptoccocus pyogenes that can cause various infections in humans, from streptococcal pharyngitis (strep throat) to necrotizing fasciitis (flesh-eating disease).
Similarities: Both genera belong to phylum Firmicutes that includes Gram-positive non-motile cocci with low GC content that do NOT form endospores. Both genera include some species that can produce exotoxins and are human pathogens.
Differences: Genus Staphylococcus includes salt-tolerant, catalase-positive facultative anaerobic cocci growing in clusters. Streptococci are part of human normal flora. Principal human pathogen is Staphylococcus aureus, which is also a part of human normal flora. Strains of S. aureus can cause in humans wide variety of infections, from boils to scalded skin syndrome. Genus Streptococcus includes salt-sensitive, catalase-negative aerotolerant cocci that are growing in chains. Streptococci are not part of human flora, but they are often carried asymptomatically. Principal human pathogen is Streptoccocus pyogenes that can cause various infections in humans, from streptococcal pharyngitis (strep throat) to necrotizing fasciitis (flesh-eating disease).
2. [21-02] Compare cellular properties of Staphylococcus aureus and Streptococcus pyogenes. Name diseases they cause – Lecture 9, Slides 7 –
Staphylococcus aureus is salt-tolerant, coagulase-positive, catalase-positive cocci growing in clusters. They are facultative anaerobes that can produce various virulence factors, like capsule, adhesins (clumping factor A, fibronectin-binding protein A), proteins covering bacterial cells with human proteins (coagulase, protein A), various enzymes and toxins. It can form biofilm. Depending on set of virulence factors produced, strains of S. aureus can cause various infectious diseases in humans, from boils to food poisoning, to pneumonia and to scalded skin syndrome.
Streptococcus pyogenes is salt-sensitive, coagulase-negative, catalase-negative cocci growing in chains. They are aerotolerant bacteria that can produce various virulence factors, like non-antigenic capsule, adhesins (M protein, protein F), protein covering bacterial cells with human proteins (protein G), various enzymes and toxins. It can form biofilm. Depending on set of virulence factors produced, strains of S. pyogenes can cause various infectious diseases in humans, from impetigo, to streptococcal pharyngitis, to necrotizing fasciitis. Due to frequent very serious complications, even mild infection caused by S. pyogenes MUST BE TREATED with antibiotics.
Staphylococcus aureus is salt-tolerant, coagulase-positive, catalase-positive cocci growing in clusters. They are facultative anaerobes that can produce various virulence factors, like capsule, adhesins (clumping factor A, fibronectin-binding protein A), proteins covering bacterial cells with human proteins (coagulase, protein A), various enzymes and toxins. It can form biofilm. Depending on set of virulence factors produced, strains of S. aureus can cause various infectious diseases in humans, from boils to food poisoning, to pneumonia and to scalded skin syndrome.
Streptococcus pyogenes is salt-sensitive, coagulase-negative, catalase-negative cocci growing in chains. They are aerotolerant bacteria that can produce various virulence factors, like non-antigenic capsule, adhesins (M protein, protein F), protein covering bacterial cells with human proteins (protein G), various enzymes and toxins. It can form biofilm. Depending on set of virulence factors produced, strains of S. pyogenes can cause various infectious diseases in humans, from impetigo, to streptococcal pharyngitis, to necrotizing fasciitis. Due to frequent very serious complications, even mild infection caused by S. pyogenes MUST BE TREATED with antibiotics.
3. [21-03] Besides capsules, what are other virulence factors of S. aureus and S. pyogenes preventing killing of bacterial cells by phagocytes? – Lecture 9, Notes of Slides 5, 6, 8 –
Virulence factors of S. aureus: Protein A binds IgG inverted; Leukocidin is secretory toxin that kills phagocytes by forming pores in their plasma (cytoplasmic) membrane. Staphyloxantin neutralizes hydrogen peroxide produced by attacking phagocyte; Biofilm interferes with ingestion of bacteria by phagocytes.
Virulence factors of S. pyogenes: Protein G binds IgG inverted; M protein inhibit activity of C3 convertase thus preventing activation of compliment system and interfering with attraction of phagocytes to the site of infection.
Virulence factors of S. aureus: Protein A binds IgG inverted; Leukocidin is secretory toxin that kills phagocytes by forming pores in their plasma (cytoplasmic) membrane. Staphyloxantin neutralizes hydrogen peroxide produced by attacking phagocyte; Biofilm interferes with ingestion of bacteria by phagocytes.
Virulence factors of S. pyogenes: Protein G binds IgG inverted; M protein inhibit activity of C3 convertase thus preventing activation of compliment system and interfering with attraction of phagocytes to the site of infection.
4. [21-04] Describe the functions of virulence factors involved in covering the cells of S. aureus and S. pyogenes by human proteins – Lecture 9, Slides 5, 6, 8 –
Virulence factors of Staphylococcus aureus – Protein A binds IgG inverted thus interfering with phagocytosis (prevents ingestion); Clumping factor A binds to fibrin, fibrinogen, plastic devices; FnBPA (fibronectin-binding protein A) binds to acellular tissue substances and plastic devices.; Coagulase deposit human proteins on bacterial cell and, thus interfering with phagocytosis. It is found in the most virulent strains.
Virulence factors of Streptococcus pyogenes – Protein G binds IgG inverted thus interfering with phagocytosis (prevents ingestion); M protein acts as adhesin but it also inhibits the activity of C3 convertase, thus preventing activation of compliment system and interfering with attraction of phagocytes to the site of infection.; Protein F is fibronectin-binding protein.
Virulence factors of Staphylococcus aureus – Protein A binds IgG inverted thus interfering with phagocytosis (prevents ingestion); Clumping factor A binds to fibrin, fibrinogen, plastic devices; FnBPA (fibronectin-binding protein A) binds to acellular tissue substances and plastic devices.; Coagulase deposit human proteins on bacterial cell and, thus interfering with phagocytosis. It is found in the most virulent strains.
Virulence factors of Streptococcus pyogenes – Protein G binds IgG inverted thus interfering with phagocytosis (prevents ingestion); M protein acts as adhesin but it also inhibits the activity of C3 convertase, thus preventing activation of compliment system and interfering with attraction of phagocytes to the site of infection.; Protein F is fibronectin-binding protein.
5. [21-05] Diphtheria – describe signs and symptoms; describe etiological agent and its virulence factors – Lecture 9, Slides 12, 13, –
Signs & symptoms: Mild sore throat → fatigue, malaise, barking cough → Bull neck, whitish pseudo-membrane formed on tonsils/pharynx, bluish color of skin, difficulty breathing
Etiological agent: Corynebacterium diphtheriae (Gram-positive bacillus, noncapsulated, nonmotile)
Virulence factors: Diphthin – IgA protease, Diphtheria toxin – A-B toxin inhibits protein synthesis in targets cells by binding to EF-2.
Virulence factors: Diphthin – IgA protease, Diphtheria toxin – A-B toxin inhibits protein synthesis in targets cells by binding to EF-2.
6. [21-06] Diphtheria – describe pathogenesis and epidemiology – Lecture 9, Slides 13, 14
Pathogenesis: Corynebacterium diphtheriae is part of normal body flora → Undergoes lysogenic conversion with ß-virus (bacteriophage) → transformed bacteria produces diphtheria toxin → Inactive A-B toxin enters bloodstream and spreads → B part of toxin binds to receptor on target cell → cell uptakes toxin via endocytosis → A part cleaved from A-B → A part of toxin enters cytosol and inhibits protein synthesis by binding to elongation factor 2 (EF2) → inhibits ribosome movement along mRNA (Targets: kidneys, heart muscle, nervous system).
Pathogenesis: Corynebacterium diphtheriae is part of normal body flora → Undergoes lysogenic conversion with ß-virus (bacteriophage) → transformed bacteria produces diphtheria toxin → Inactive A-B toxin enters bloodstream and spreads → B part of toxin binds to receptor on target cell → cell uptakes toxin via endocytosis → A part cleaved from A-B → A part of toxin enters cytosol and inhibits protein synthesis by binding to elongation factor 2 (EF2) → inhibits ribosome movement along mRNA (Targets: kidneys, heart muscle, nervous system).
Epidemiology: disease is contagious, notifiable disease
Reservoir – humans (asymptomatic cases, people with active disease, people recovering from disease (still carrying bacteria), contaminated fomites
Transmission – Respiratory droplets, direct contacts (Handshake), indirect contact (fomites)
Number of cases reported – From 1980-2018 only 60 cases
Mortality rate –20% death rate even if promptly treated
7. [21-07] Diphtheria – describe prevention and treatment – Lecture 9, Slides 15, 16 –
Prevention: C. diphtheriae is part or normal microbiota → DTaP vaccine (Diphtheria toxoid + tetanus toxoid + acellular pertussis) → body forms antibodies to neutralize weakened diphtheria toxoid → later diphtheria toxin also neutralize.
DTaP part of US immunization schedule, booster every 10 years
Treatment: Diphtheria Antitoxin (Neutralize toxin in bloodstream, requires early application) + Antibiotics (Kill pathogen to prevent production of new toxin, usually penicillin/erythromycin).
DTaP part of US immunization schedule, booster every 10 years
Treatment: Diphtheria Antitoxin (Neutralize toxin in bloodstream, requires early application) + Antibiotics (Kill pathogen to prevent production of new toxin, usually penicillin/erythromycin).
8. [21-08] Pertussis – describe signs and symptoms; describe etiological agent – Lecture 9, Slide 20 –
Signs & Symptoms: 3 stages of symptoms – (1) Catarrhal stage = Similar to common cold w/ runny nose and no fever (2) Paroxysmal stage = Severe cough spasms w/ forceful inspiration, fever, vomiting and possible seizure (3) Convalescence stage = Recovery from disease
Etiological agent: Bordetella pertussis (Gram-negative coccobacillus, obligate aerobe)
Virulence factors: Capsule – Interferes with phagocytosis, Toxins – (1) Pertussis toxin (PTx) = Adhesin, A-B toxin leads to increased production of cAMP → increases mucus production, decrease phagocytes natural killers (2) Invasive adenylate cyclase = Membrane damaging toxin and enzyme → lysis of accumulated leukocytes, increased intracellular cAMP → increase mucus production, inhibit T cell function (3) Tracheal cytotoxin = cillostasis, ciliated cells stop beating → cell death, pyrogenic (fever inducing).
Etiological agent: Bordetella pertussis (Gram-negative coccobacillus, obligate aerobe)
Virulence factors: Capsule – Interferes with phagocytosis, Toxins – (1) Pertussis toxin (PTx) = Adhesin, A-B toxin leads to increased production of cAMP → increases mucus production, decrease phagocytes natural killers (2) Invasive adenylate cyclase = Membrane damaging toxin and enzyme → lysis of accumulated leukocytes, increased intracellular cAMP → increase mucus production, inhibit T cell function (3) Tracheal cytotoxin = cillostasis, ciliated cells stop beating → cell death, pyrogenic (fever inducing).
9. [21-09] Pertussis – describe pathogenesis and epidemiology – Lecture 9, Slides 21, 22
Pathogenesis: Bordetella pertussis enters respiratory tract through inhaled droplets → attaches to ciliated cells using adhesins: pertussis toxin (PTx) and filamentous hemagglutinin (FHA) → colonizes nasopharynx, trachea, bronchi, bronchioles and forms dense masses → production of toxins: pertussis toxin & invasive adenylate cyclase (IAC) increase mucous production, IAC kills leukocytes, tracheal cytotoxin causes ciliostasis and kills ciliated cells → mucous build up causes whooping cough reflex (Pneumonia as secondary infection common)
Epidemiology: disease is highly contagious, notifiable disease
Reservoir – humans only
Transmission – Airborne disease transported via respiratory droplets
Number of Cases Reported – 50% of cases occur in infants, # of cases on the rise in US from 1,700 (1980) to 12,000 (2009).
Mortality rate – 0.5% of hospitalize children
Pathogenesis: Bordetella pertussis enters respiratory tract through inhaled droplets → attaches to ciliated cells using adhesins: pertussis toxin (PTx) and filamentous hemagglutinin (FHA) → colonizes nasopharynx, trachea, bronchi, bronchioles and forms dense masses → production of toxins: pertussis toxin & invasive adenylate cyclase (IAC) increase mucous production, IAC kills leukocytes, tracheal cytotoxin causes ciliostasis and kills ciliated cells → mucous build up causes whooping cough reflex (Pneumonia as secondary infection common)
Epidemiology: disease is highly contagious, notifiable disease
Reservoir – humans only
Transmission – Airborne disease transported via respiratory droplets
Number of Cases Reported – 50% of cases occur in infants, # of cases on the rise in US from 1,700 (1980) to 12,000 (2009).
Mortality rate – 0.5% of hospitalize children
10. [21-10] Pertussis – describe prevention and treatment – Lecture 9, Slide 23 –
Prevention: DTaP vaccine (Diphtheria toxoid + tetanus toxoid + acellular pertussis) → body products antibodies to acellular portions of pertussis.
Antibiotic prophylaxis – Antibiotics given to anyone in contact with infected person.
Quarantine – Up to 6 weeks to prevent spread of disease.
Treatment: Antibiotics ONLY effective during catarrhal stage of disease (erythromycin/sulfa drugs preferred). Antibiotics ineffective during paroxysmal stage.
Prevention: DTaP vaccine (Diphtheria toxoid + tetanus toxoid + acellular pertussis) → body products antibodies to acellular portions of pertussis.
Antibiotic prophylaxis – Antibiotics given to anyone in contact with infected person.
Quarantine – Up to 6 weeks to prevent spread of disease.
Treatment: Antibiotics ONLY effective during catarrhal stage of disease (erythromycin/sulfa drugs preferred). Antibiotics ineffective during paroxysmal stage.
11. [21-11] Tuberculosis – describe signs, symptoms; describe etiological agent – Lecture 9, Slide 24 –
Signs & symptoms: Loss of appetite & fatigue → chest pain, slight fever with night sweats, progressive weight loss, chronic productive cough (if sputum has blood TB is active form, individual is infective to others).
Etiological agent: Mycobacterium tuberculosis and other mycobacterium species (M. bovis, M. africanum, M. canetti, M. microtti.
Virulence factor: Components of cell wall → acid-fast, mycolic acid (extremely hydrophobic cell wall)
Signs & symptoms: Loss of appetite & fatigue → chest pain, slight fever with night sweats, progressive weight loss, chronic productive cough (if sputum has blood TB is active form, individual is infective to others).
Etiological agent: Mycobacterium tuberculosis and other mycobacterium species (M. bovis, M. africanum, M. canetti, M. microtti.
Virulence factor: Components of cell wall → acid-fast, mycolic acid (extremely hydrophobic cell wall)
12. [21-12] Tuberculosis – describe pathogenesis and diagnostics – Lecture 9, Slide 25, 29
Pathogenesis: Damage done via Type IV Delayed allergy reaction.
Pathogen enters lung alveoli → Ingested by pulmonary macrophage → TB cell wall prevents fusion of phagosome and lysosome → Mycobacterium survive and multiply inside macrophage, forming primary site of infection → More macrophages are attracted to site of infection, fuse with already infected macrophages, BUT fail to kill bacteria → more macrophages are attracted and form protective layer, tubercle → formation of tubercle results in chronic inflammation reaction → Slow maturation of tubercle and calcification → IF tubercle breaks up, leaks blood and bacteria into lungs → Microbe can spread to other parts of body forming secondary site of infection.
Diagnostics: (Tuberculin/Montoux/PPD test) Standard dose of tuberculin antigen injected intradermally → reaction read in 48-72 hrs for induration diameter → IF NO induration or <5mm = negative, IF induration ≥5mm = positive → X-ray of chest take for positive confirmation of TB.
(QuantiFERON®-TB Gold test) Blood test → Good for patients who have taken BCG vaccine.
Pathogenesis: Damage done via Type IV Delayed allergy reaction.
Pathogen enters lung alveoli → Ingested by pulmonary macrophage → TB cell wall prevents fusion of phagosome and lysosome → Mycobacterium survive and multiply inside macrophage, forming primary site of infection → More macrophages are attracted to site of infection, fuse with already infected macrophages, BUT fail to kill bacteria → more macrophages are attracted and form protective layer, tubercle → formation of tubercle results in chronic inflammation reaction → Slow maturation of tubercle and calcification → IF tubercle breaks up, leaks blood and bacteria into lungs → Microbe can spread to other parts of body forming secondary site of infection.
Diagnostics: (Tuberculin/Montoux/PPD test) Standard dose of tuberculin antigen injected intradermally → reaction read in 48-72 hrs for induration diameter → IF NO induration or <5mm = negative, IF induration ≥5mm = positive → X-ray of chest take for positive confirmation of TB.
(QuantiFERON®-TB Gold test) Blood test → Good for patients who have taken BCG vaccine.
Epidemiology: Contagious (active form), notifiable disease
Reservoir – Humans ONLY
Transmission – Respiratory droplets (Inhaled microbes → ID50 = 10), animals (cow milk)
Number of cases reported – Worldwide TB cases have doubled to 6 million (80% of new cases are from Brazil, China, India, Malaysia, and Russia), US decrease from 25,000 (1993) to 9,400 (2014)
Reservoir – Humans ONLY
Transmission – Respiratory droplets (Inhaled microbes → ID50 = 10), animals (cow milk)
Number of cases reported – Worldwide TB cases have doubled to 6 million (80% of new cases are from Brazil, China, India, Malaysia, and Russia), US decrease from 25,000 (1993) to 9,400 (2014)
Mortality rate – Asymptomatic in 90% cases →10% cases develop into active TB (IF secondary site of infection untreated, almost 100% mortality)
Prevention: BCG (Bacillus Calmette–Guérin) vaccine widely used in many parts of world, 50%-71% effective (NOT in US) → US uses Tuberculin test to detect those previously exposed to pathogen.
Direct Observed Therapy Short Course (DOTS) –Method to insure medication compliance from patient, healthcare worker watches patient take each dose of medication.
Treatment: After positive confirmation of tuberculosis → First 2 months: Rifampin, Isoniazid, Pyrazinamide, Ethambutol → Next 4-7 months: Isoniazid and Rifampin.
Bactericidal antibiotics over long period (6 months+), cocktail of drugs to reduce hydrophobic cell wall (Ethambutol, Isoniazid, Pyrazinamide) and bactericidal antibiotic (Rifampin – Inhibit nucleic acid synthesis) or (Streptomycin – inhibit protein synthesis).
Direct Observed Therapy Short Course (DOTS) –Method to insure medication compliance from patient, healthcare worker watches patient take each dose of medication.
Treatment: After positive confirmation of tuberculosis → First 2 months: Rifampin, Isoniazid, Pyrazinamide, Ethambutol → Next 4-7 months: Isoniazid and Rifampin.
Bactericidal antibiotics over long period (6 months+), cocktail of drugs to reduce hydrophobic cell wall (Ethambutol, Isoniazid, Pyrazinamide) and bactericidal antibiotic (Rifampin – Inhibit nucleic acid synthesis) or (Streptomycin – inhibit protein synthesis).
15. [21-15] Influenza – describe etiological agent. What are antigenic drift and antigenic shift? Why is influenza virus undergoing antigenic drift and antigenic shift? – Lecture 9, Slides 36-37 –
Signs & Symptoms: Short incubation period (1-2days) → headache, fever, muscle pain, dry cough → acute symptoms abate within a week, though cough and fatigue may linger
Etiological agent: Influenza virus types A, B, C – Single-stranded, segmented RNA genome (A & B – 8 segments, C – 7 segments). Envelop has two essential proteins: hemmagglutinin (viral adhesin) can agglutinate RBC & neuraminidase an enzyme that is involved In budding of newly assembled viral particles from host cells.
Virulence factors: Hemmagglutinin and neuraminidase proteins.
Antigens of the virus constantly changing due to antigenic drift and antigenic shift.
Antigenic drift – Characteristic of RNA viruses, mutation to genes by RNA polymerase because no proof reading capability = multiple errors. Viral constantly changing at slow pace.
Antigenic shift – Result of infection of cell by two different viral strains at the same time → mixing of viral genes (RNA segments) → new recombinant viral strains.
Pathogenesis: Virus enters respiratory track → attaches to epithelial cells via hemagglutinin → Virus is temperate and slowly replicates in host cell → New virions released via budding → infected cells eventually die → inflammation reaction (sets off signs and symptoms of disease) → Humoral immune response (antibodies) quickly suppress viral replication.
Epidemiology: Contagious, notifiable disease, zoonosis
Reservoir –Humans, animals, birds
Transmission –Respiratory droplets, contaminated fomites (touching face after touching fomite)
Number of cases reported –Outbreaks occur annually worldwide (~500,000 deaths reported worldwide, 10,000-40,000 in USA)
Mortality rate – 1.6 deaths/100,000
Prevention: Vaccine produced from attenuated viruses grown in embryonic eggs.
Quadrivalent (4 strains), Trivalent (3 strains). (80-90% effective)
Treatment: Various antiviral drugs available (70-90% effective if taken early)
Neurominidase inhibitors –Prevent budding of viral particales off the cells (Ex: Tamuflu, Relenza, Inavir)
M2 proton channel inhibitors – Prevent replication of virus inside the cell (Ex: Amantidine, Rimantidine)
Signs & Symptoms: Short incubation period (1-2days) → headache, fever, muscle pain, dry cough → acute symptoms abate within a week, though cough and fatigue may linger
Etiological agent: Influenza virus types A, B, C – Single-stranded, segmented RNA genome (A & B – 8 segments, C – 7 segments). Envelop has two essential proteins: hemmagglutinin (viral adhesin) can agglutinate RBC & neuraminidase an enzyme that is involved In budding of newly assembled viral particles from host cells.
Virulence factors: Hemmagglutinin and neuraminidase proteins.
Antigens of the virus constantly changing due to antigenic drift and antigenic shift.
Antigenic drift – Characteristic of RNA viruses, mutation to genes by RNA polymerase because no proof reading capability = multiple errors. Viral constantly changing at slow pace.
Antigenic shift – Result of infection of cell by two different viral strains at the same time → mixing of viral genes (RNA segments) → new recombinant viral strains.
Pathogenesis: Virus enters respiratory track → attaches to epithelial cells via hemagglutinin → Virus is temperate and slowly replicates in host cell → New virions released via budding → infected cells eventually die → inflammation reaction (sets off signs and symptoms of disease) → Humoral immune response (antibodies) quickly suppress viral replication.
Epidemiology: Contagious, notifiable disease, zoonosis
Reservoir –Humans, animals, birds
Transmission –Respiratory droplets, contaminated fomites (touching face after touching fomite)
Number of cases reported –Outbreaks occur annually worldwide (~500,000 deaths reported worldwide, 10,000-40,000 in USA)
Mortality rate – 1.6 deaths/100,000
Prevention: Vaccine produced from attenuated viruses grown in embryonic eggs.
Quadrivalent (4 strains), Trivalent (3 strains). (80-90% effective)
Treatment: Various antiviral drugs available (70-90% effective if taken early)
Neurominidase inhibitors –Prevent budding of viral particales off the cells (Ex: Tamuflu, Relenza, Inavir)
M2 proton channel inhibitors – Prevent replication of virus inside the cell (Ex: Amantidine, Rimantidine)
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