Microbiology Lecture 6 Review: Chapter 16,19 Host-Microbe Actions & Epidemiology

Lecture Review 6

Chapter 16 - Microbe-Host Interactions

1.    [16-01] The course of infectious disease. Compare Incubation period, Prodromal phase, Illness, Decline, Convalescence – Lecture 6, Slide 5 –

(1) Incubation period: Time between initial exposure and onset of 1^st signs & symptoms, lasts few hours to two weeks, patient may be infective to others (esp. viral respiratory infections).

(2) Prodromal phase: Short period of early mild symptoms, # of pathogens enough to start causing damage to host, immune system activated, patient becomes infective to others.

(3) Illness: Stage of disease when signs and symptoms most prominent & severe, high microbe #, immune system mounting response with antibodies, antibody titer rising.

(4) Decline: Stage of disease when patient starts feeling relief from symptoms, immune response is mounted & strong, eliminating pathogen from host, many resources expended = high risk of secondary infections (complications).

(5) Convalescence: Stage of recuperation and recovery, if disease is contagious patient can still be infective, best time for disease to mutate.

2.    [16-02] Compare Koch’s postulates against molecular postulates – Lecture 6, Slide 8 –

Koch’s postulates – To establish cause (etiology) of the disease

·      Microbe must be found in all cases of the disease.

·      Microbe must be isolated from diseased host in pure culture.

·      Microbe must cause same disease for healthy host upon injection.

·      Microbe must be isolated again from experimentally diseased animal.

Molecular postulates – To establish virulence factors of pathogen

·      Gene for virulence factor(s) must be present and expressed in strain.

·      Disruption of gene(s) expression should reduce/abolish pathogenicity of strain.

·      Expression of gene(s) of virulence factor(s) in non-pathogenic strains should change them into pathogenic.

·      Antibodies against virulence factors should be protective.

Virulence factors: Molecules & structures that define the pathogenicity of microbe.

o   Adhesins → Molecules responsible for microbial attachment to host.

o   Capsules → Extracellular structure that interferes with phagocytosis.

o   Antigenic variations → Continuously alter surface proteins.

o   Enzymes → Break down host tissue and molecules (Eg. Hyaluronidase)

o   Antibody modifying proteins → Digestion of antibodies (IgA proteases), inversion of antibodies

o   Waxy components of cell wall → acid-fast bacteria (mycobacterium)

3.    [16-03] Describe four exceptions from Koch’s postulates. Give microbial examples for each exception – Lecture 6, Slide 10 –

·      Pathogen is difficult or impossible to grow in culture (Treponema pallidum – syphilis).

·      Pathogen has human as unique host (HIV grows in humans only).

·      Multiple microbes cause the SAME disease (Mycoplasma pneumoniae, Streptococcus pneumoniae, Neisseria pneumoniae = all cause pneumonia).

·      SAME microbe can cause multiple diseases (Streptococcus pyogenes – impetigo, scarlet fever, toxic shock syndrome, necrotizing fasciitis).

4.    [16-04] Describe the breaching and infection of mucous membrane by Shigella spp. Name virulence factors involved in this mechanism – Lecture 6, Slides 13, 14 –

Infectious disease development (slide11)

(1) Establishing infection: Shigella is ingested by host.

(2) Breaching barriers & invasion: Microfold (M) cells in small intestine take in Shigella and present to macrophage, which takes in Shigella. Shigella kills macrophage and uses TYPE III secretion system to inject effector molecules to cause membrane ruffling and gets into cell.

(3) Avoiding host defenses: Shigella inhibits formation of phagolysosome and survives in macrophage. Kills macrophage by secretory exotoxin.

(4) Damage to host: Once inside epithelial cells of guts, shigella multiples resulting in tissue destruction.

(5) Exit of pathogen from the host: Shigella exits host via GI tract and spreads to next host through fecal-oral route.

5.    [16-05] Compare the general properties of exotoxins and endotoxins. Give examples – Lecture 6, Slide 16 –

Exotoxins: Toxin proteins produced by both gram-positive and gram-negative bacteria that are target specific and highly potent. Most are sensitive to heat inactivation and can be used to form toxoids suitable for immunization.

Endotoxins: Lipopolysaccharide part of gram-negative bacteria cell wall. Cannot be heat inactivated and have a non-specific action (not very toxic, unless in large numbers).

6.    [16-06] Describe the mechanism of type I exotoxin action. Give examples – Lecture 6, Slides 17, 19 –

AKA “superantigens” Cell surface-active → binds and links two cells together (T helper cell receptor and MHC II of APC cell) → activation of up to 50% of all T helper cells → massive release of cytokines and interleukins (cytokine storm) → widespread vasodilation of blood vessels and massive loss of fluids from circulatory system → Symptoms: rashes, nausea, vomiting, diarrhea, fever, shock, multi-organ failure, death

EX: Enterotoxin TSST-1 of S. aureus and Pyrogenic exotoxins SpeA and SpeC of S. pyogenes.

7.    [16-07] Describe cholesterol-dependent cytolysin action. Give examples – Lecture 6, Slides 18, 19 –

Under Type II exotoxins: membrane damaging → Cholestrol-dependent cytolysins → Bind to cholesterol on human host cells → form large pores membranes of targeted cells causing lysis (Ex: Streptolysin O and streptolysin S of Streptococcus pyogenes; alpha toxin and leukocidin of Staphylcoccus aureus; pneumolysis of Streptococcus pneumoniae).

8.    [16-08] Describe AB exotoxin action. Give examples – Lecture 6, Slides 18, 19 –

Under Type III exotoxins: intracellular → AB toxins → Produced and secreted in inactive form with A and B subunits connected → Toxin binds to receptor via B subunit → Subunit A is cleaved from subunit B and becomes active → Subunit A interferes with cellular function and kills cell.

(Ex: Diphtheria toxin of Corynebacterium diphtheriae, Shiga toxin of E. coli inhibit protein synthesis, cholera toxin activates adenylate cyclase leading to increase cAMP production and loss of fluids, botulinum toxin of Clostridium botulinum interfere with signal transduction between muscles and neurons).

Chapter 19 - Epidemiology

9.    [19-01] Distinguish between non-contagious and contagious infectious diseases – Lecture 6, Slides 6, 21, 25 –

Non-contagious: High ID50, Transmitted through special routes = Non-causal body fluids (eg. blood or semen), vectors, vehicles.

Contagious: Low ID50, Transmitted through direct contact, indirect contact (objects in contact with infected), causal body fluids (respiratory droplets).

10. [19-02] Describe the chain of infection for gastroenteritis caused by Salmonella – Lecture 6, Slide 22 –
Reservoir: Domestic animals, reptiles, poultry
Portal Exit:Feces, fecal contact
Transmission: GI tract,fecal-oral route
Portal Entry:Mouth
Susceptible host:humans (intestines)

11. [19-02] Distinguish between portal of entry and preferred portal of entry. Give examples for Streptococcus pneumoniae – Lecture 6, Slide 24 –

Portal of entry: Routes used by pathogen to enter host (same microbe may used different portals).

Preferred portals of entry: Route used by pathogen to enter host & cause disease.

Ex: Staphylococus pneumoniae causes pneumonia in lungs, BUT no disease in GI tract.

12. [19-04] Describe Pathogen properties, Host properties affecting spread of disease – Lecture 6, Slide 27 –

Pathogen properties:

·      Virulence – Strains that have additional factors that increase pathogenicity (refer Q2)

·      Incubation period – How long till symptoms kick in

·      Infectious dose (ID₅₀) – How many cells required to cause disease

Host Properties:

·      Anatomy – Body anatomy difference (females more likely to urogenital infections)

·      Immunity – Innate and Adaptive immunity of human body system

·      Genetics – Genetic predisposition for certain health issues

·      Health & Behavior – General body health and human choices

13. [19-05] Using example of Bacillus anthracis and Yersinia pestis reviewed in lecture, explain how portal of entry can affect ID₅₀ and transmission of the disease – Lecture 6, Slide 28 –  

Depending on portal of entry bacteria can cause different pathologies.

Bacillus anthracis = Gram-positive bacillus, obligate aerobe

Three portals of entry:

Cutaneous (skin) – ID50 = 10 endospores

Inhalation – ID50 = 10,000 endospores

Ingestion – ID50 = 250,000 endospores

Since Bacillus anthracis spores lack methods to break through mucosal lining they require a significantly higher amount of cells than if through a break in the skin. Break in the skin exposes blood, which provides enough environmental growth factors for the endospore to germinate.

Yersinia pestis= Gram-negative coccobacillus, facultative anaerobe

Two portals of entry:

Vector (flea bite) – Microbe ends up in lymph node and leads to formation of swelled lymph nodes “buboes.” Bubonic plague, non-contagious disease, 50-75% mortality rate.

Inhalation – Microbe ends up in lungs and leads to hemoptysis, cough up blood. Pneumonic plague, contagious disease, over 90% mortality rate.

The portals entry also reflects the portals of exit. Plague brought through fleabites leaves through fleabites and remains non-contagious. However, plague in the lungs can also spread through respiratory droplets owning to colonization of the respiratory system by the bacteria.

14. [19-06] Using multistate Salmonella outbreak described in MMWR, 2012,61(46);944-947 and reviewed in lecture, describe the importance of epidemiological studies and surveillance of the disease – Lecture 6, Slide 30 and corresponding article –

Descriptive study

·      Person: 22 patients, aged 20-87 years old

·      Place: DC, MD, VA, DE, NJ, NH, CA, MI

·      Time: August 19 – November 21, 2011

Analytical study

·      All 22 people have visited Washington DC

·      20 reported eating at restaurants in Washington DC

·      16 have eaten Mediterranean food, 10 – eating hummus

Experimental studies

·      Hummus samples collected from restaurants on 11/8/2011 tested positive for Salmonella à Single source of origin. On 11/18 Department of Health and Human Services issued an embargo on humus from that particular producer.

Similar outbreak in Canada Spring 2012. Traced back to sesame seeds from Lebanon. FDA mandated all products from this manufacturer undergo Salmonella testing prior to USA entry.

15. [19-07] Define term “nosocomial infection”. Discuss reservoirs of nosocomial infections. Discuss routes of transmission and prevention of nosocomial infections – Lecture 6, Slide 35-37 –

Nosocomial infection: Healthcare Associated Infection (HAI) → Infection acquired in hospital.

Reservoirs of nosocomial infections:

·      Other patients with infectious diseases

·      Normal flora of body → turns opportunistic infection

·      Healthcare workers spreading the disease

·      Hospital environment → floors and air can harbor microbes

Routes of transmission:

·      Medical devices

·      Direct contact

·      Airborne

Prevention of nosocomial infections:

·      Hand hygiene → Most basic, vital form of prevention

·      Respiratory hygiene → Avoiding spread of respiratory droplets

·      Personal protective equipment → Using gowns, gloves, and masks

·      Patient placement → Quarantine infectious disease patients

·      Care of environment → Careful disinfection and sterilization of certain surfaces

·      Equipment/instrument safe handling → Making sure that equipment is not

·      Safe injection practices

·      Textiles and laundry → Use of quads for detergent to kill microbes

·      Worker safety