Bacterial Pathogenesis I - L7 Flashcards

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1
Q

What is bacterial pathogenesis?

A

the mechanism by which a bacterial pathogen produces disease

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2
Q

What is a bacterial pathogen?

A

a bacteria that is capable of causing disease in a host

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3
Q

Virulent pathogen

A

exceedingly pathogenic organism

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4
Q

avirulent organism

A

not pathogenic

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5
Q

attenuated pathogen

A

less pathogenic organism

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6
Q

primary pathogen

A

disease causing pathogen that can cause disease even in a healthy host

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7
Q

opportunistic pathogen

A

can cause disease only in a compromised host; do not cause disease under normal conditions but can cause disease under special conditions

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8
Q

How do you show that a suspected pathogen is the cause of a particular disease?

A

Koch’s Postulates

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9
Q

What are Koch’s Psotulates?

A
  1. the organism must be present in every case of a disease (but absent from healthy)
  2. the organism must be isolated from diseased host and cultivated in pure culture
  3. the cultivated organism must cause the same disease when inoculated into a naive host
  4. the organism must be recovered from the newly diseased host
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10
Q

What are problems with Koch’s Postulates?

A

a. some bacteria and all viruses can only be grown in eukaryotic cells
b. some agents cannot be cultured or no suitable animal model is available

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11
Q

mutualistic

A

both organisms benefit from the relationship

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12
Q

commensalistic

A

one organism benefits while the other neither benefits or is harmed

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13
Q

parasitic

A

one organism benefits (parasite) from the relationship and the other organism (host) is harmed

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14
Q

colonization

A

establishment and multiplication of a microorganism (pathogen or non-pathogen) in a host

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15
Q

infection

A

refers to the multiplication of a PATHOGEN in a host with or without disease (ex. asymptomatic carriers)

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16
Q

disease

A

occurs when an infected host is injured or damaged in a manner that impairs host function

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17
Q

When does bacteria colonization begin?

A

during or soon after birth

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18
Q

What is normal flora/microbiota/microbiome?

A

bacteria that establish permanent colonies inside of on the body without producing disease

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19
Q

bacterial antagonism

A

the normal flora can prevent colonization by pathogens

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20
Q

How many microorganisms normally reside in or on the body?

A

1x10^14 in total; 500 to 1000 species of bacteria live in the human gut, with a similar number on the skin

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21
Q

What kind of relationship do we have with normal flora?

A

previously commensalism;

currently it plays a critical role in our health and development

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22
Q

Characteristics of skin flora?

A
  • a dry, acidic environment
  • primarily moist areas colonized (associated with sweat glands)
  • mainly gram positive bacteria
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23
Q

Characteristics of oral cavity flora?

A
  • dental plaque = biofilm

- dental procedures can allow bacteria into bloodstream

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24
Q

Characteristics of GI flora?

A
  • stomach kills most bacteria

- intestine = hella, higher pH

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25
Q

What are the benefits of the microbiota?

A

help digest food, required for healthy immune system, synthesis of vitamin B12 and vitamin K

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26
Q

What affects microbiota composition?

A

antibiotics, stress, changes in diet

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27
Q

what are probiotics?

A

supplemental beneficial bacteria that can help restore normal balance and composition of the microbiota

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28
Q

Characteristics of respiratory tract flora?

A
  • upper heavily colonized

- lower essentially sterile

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29
Q

what is the mucociliary elevator?

A

cilia and mucous trap bacteria in the throat and move them to the mouth for swallowing to the stomach

30
Q

Characteristics of urogenital tract flora?

A
  • kidneys and bladder normally sterile

- outer parts are colonized with normal flora

31
Q

Why are antibiotics such an issue right now?

A
  • average kid gets 10-20 courses before 18
  • they target pathogens AND beneficial bacteria
  • open doors for opportunistic pathogens like MRSA and Clostridium difficile
  • use in food is affecting humans as well
32
Q

What does a pathogen have to do to cause disease?

A
  1. contact the host
  2. colonize/infect the host
  3. evade host defense systems
  4. damage host cells/tissues
33
Q

virulence factors

A

factors responsible for the virulence of a pathogen

34
Q

Types of virulence factors?

A

adhesins, invasins, evasins, toxins, and degradative enzymes

35
Q

Where are virulence factors found?

A

on mobile genetic elements or pathogenicity islands

36
Q

pathogenicity islands

A

chromosome islands that have different GC/AT ratio that the rest of the chromosome

37
Q

Old School host interaction

A

bacteria contact host cells/tissues
attach, grow and multiply locally or spread to deeper tissues
release toxins

38
Q

new school host interaction

A

pathogens employ complex virulence strategies to manipulate host cell responses and to promote their survival/transmission (T3SS)

39
Q

Enteropathogenic E. coli (EPEC)

A

causative agent of infantile diarrhea; interaction of organism with intestinal epithelial cells (attaching and effacing lesions)

40
Q

What are common portals of entry?

A
  • urogenital tract (STDs, UTIs)
  • digestive tract (contaminated food/water)
  • respiratory tract (airborne)
  • Conjunctiva/eye (chlamydia/trachoma)
  • damaged skin (staphylococcal infections)
  • injection (insects - parenteral route)
41
Q

How do pathogens move past colonization?

A

must adhere to eukaryotic cells or tissue and withstand host’s defenses

42
Q

Adhesins

A

bacterial cell surface proteins that bind to specific host receptors on epithelial or exposed cells

43
Q

what are the two steps of bacterial adhesion?

A
  1. Initial loose attachment
    - pili, biofilms, slime layers, LPS
  2. strong or intimate attachment
    - bacterial nonpilus adhesins
44
Q

biofilm

A

bacteria attached to surfaces in bulk, plus an extracellular polymeric substance (EPS)

45
Q

Why are biofilms important?

A

play an important role in chronic infections by helping with persistent adherence and resistance to host and antimicrobial defenses

46
Q

How do invasive bacteria spread?

A
  • releasing toxins
  • penetrating barriers to deeper tissues
  • via blood or lymph circulation
47
Q

Where do invasive bacteria spread?

A

specific organs or to whole system

48
Q

Bacteremia

A

bacteria in blood

49
Q

Septicemia

A

bacteria growing and multiplying in blood

50
Q

extracellular pathogens

A

attach to receptor molecules on host cell surface and remain extracellular (like cholera)

51
Q

intracellular pathogens

A

invade host cells and multiply inside these cells (in membrane vacuole or outside cells)

52
Q

facultative intracellular pathogens

A

can grow inside cells or outside - salmonella, shigella, listeria

53
Q

obligate intracellular pathogens

A

only grow inside eukaryotic cells - chlamydia, rickettsia

54
Q

Intracellular life advantages vs disadvantages

A
  • difficult for host to attack without autophagy or apoptosis
  • intracellular bacteria safe from antibodies, complement proteins, and some antibiotics
  • access to host cell nutrients
  • must exit cells at some point to exit host and be transmitted to a new host
55
Q

extracellular life advantages vs. disadvatages

A
  • pathogen must deal with antibodies, complement system, etc.
  • pathogen must compete with normal flora and other pathogens
  • provides greater opportunity for rapid growth, reproduction and spreading
56
Q

What defense systems do pathogens have to avoid?

A
  • destruction by phagocytosis
  • complement mediated lysis and host antibody response
  • destruction in the phagosome
  • antimicrobial peptides
  • reactive oxygen and nitrogen species
  • the cell mediated immune response
  • apoptosis
57
Q

What is complement-mediated bacterial lysis (what is the complement system)?

A

refers to a series of proteins circulating in the blood in an inactive form that can be activated by certain host or microbial products

58
Q

How can complement be activated?

A
  • antibody binding to the bacterial surface (classical pathway)
  • bacterial polysaccarides/LPS (alternative pathway)
59
Q

What is the result of the complement system?

A
  • generation of products that label or opsonize the bacteria

- results in the formation of a membrane attack complex (MAC) that lyses gram-negative bacteria

60
Q

Serum resistant bacteria

A

bacteria not killed by the complement MAC

61
Q

What are mechanisms of serum resistance?

A
  • capsules (inhibit opsonization, hide bacterial components that induce pathway)
  • modification of LPS O-antigen
  • release proteases that degrade complement components
  • binding of complement regulatory components to the bacterial surface
62
Q

How do bacteria avoid host antibody responses?

A

pathogens often coat themselves with normal host antigens (fibronectin, antibodies) or bacterial products (hyaluronic acid) that cannot be distinguished from host antigens

63
Q

antigenic variation

A

many bacteria can change the antigens of key exposed surface products (ex. Neisseria spp. pili)

64
Q

phase variation

A

bacteria can turn the expression of certain key antigens off and on during an infection

65
Q

What are two functions of bacterial products?

A
  • destroy host immune cells

- aid in spread/transmission of the infection

66
Q

What are the two general classes of toxic molecules produced?

A
  1. endotoxin (LPS) - associated with outer membrane

2. exotoxins - enzymes and toxins that are released from bacterial cells and function at a distance

67
Q

Key facts about endotoxin (LPS)?

A
  • produced by only gram-neg
  • part of cell wall
  • LPS
  • low toxicity (large dose needed)
  • heat stable
  • systemic effect
  • cannot be converted to safe form (not immunogenic)
68
Q

Key facts about exotoxins?

A
  • produced by both gram-pos and gram-neg
  • extracellular, secreted
  • proteins
  • high toxicity (hella toxic, you gon die)
  • heat labile (change in heat)
  • highly specific target/effect
  • highly immunogenic (can be inactivated and made into a vaccine/antiserum)
69
Q

How does a pathogen get to the next host?

A
  • oral-fecal route: diarrhea (EPEC, vibrio cholerae)
  • aerosols: sneezing and coughing (mycobacterium tuberculosis)
  • direct sexual contact/sexual transmission (chlamydia trachomatis)
  • other vectors (insects, etc.)
70
Q

A summary of bacterial pathogenesis:

A
  1. contact the host (transmissible)
  2. colonize/infect the host (adhere to surfaces + multiply)
  3. evade host defense systems (prevent clearance, find a niche, avoid/subvert/circumvent defenses)
  4. damage host cells/tissues (spread, release nutrients)
  5. Disseminate (transmissable - GTFO)