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+ MICB 202 Final > Bacteria Chapter 14: Type III Secretion System as VIrulence Factor > Flashcards

Bacteria Chapter 14: Type III Secretion System as VIrulence Factor Flashcards

1
Q

What are facultative intracellular pathogens?

A

pathogens that can live within or outside host cells

ie. Salmonella

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2
Q

What are obligate intracellular pathogens?

A

pathogens that must grow within host cells, and cannot be cultivated outside of their host

ie. Chlamydia

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3
Q

Why are intracellular environments good for bacteria?

A
  • rich source of nutrients and energy
  • shields from host’s immune system
  • provides protection from many antibiotics that don’t penetrate host cells
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4
Q

What immune response plays an important role in defence against intracellular pathogens?

A

cell-mediated immunity – T cell effector mechanisms and activation of macrophages

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5
Q

What is Salmonella?

A

intracellular pathogen that hides from host’s immune defences

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6
Q

What are characteristics of Salmonella?

A
  • Gram-negative
  • flagellated
  • facultatively anaerobic Bacilli
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7
Q

What are the major antigens of Salmonella?

A
  • H antigen (flagellar)
  • O antigen (somatic – cell wall)
  • K antigen (capsular)
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8
Q

What is a major antigen of the capsular antigen?

A

Vi

possessed by only a few serovars of Salmonella – particularly those that cause typhoid fever

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9
Q

How is Salmonella transmitted?

A

from feces of infected people or animals, to other people or animals via contaminated food or drink

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10
Q

What are the two main diseases associated with Salmonella?

A
  • salmonellosis

- typhoid fever

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11
Q

What is salmonellosis in human?

A

usually self-limiting gastroenteritis (diarrhea)

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12
Q

What is Salmonella enterica?

A

serovar of Salmonella

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13
Q

What are the two sub-species of Salmonella enterica?

A
  • Salmonella enterica serovar Typi (Salmonella typhi)

- Salmonella enterica serovar Typhimurium (Salmonella Typhimurium)

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14
Q

Where does Salmonella enterica cause disease?

A

intestines

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15
Q

Who is more at risk for Salmonella infections

A

individuals who produce little or no stomach acidity

Salmonella are very acid sensitive

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16
Q

How many bacteria are required to cause Salmonella infection in humans?

A
  • large amount required to infect humans with normal stomach acid
  • smaller amount required to infect humans when introduced with bicarbonate
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17
Q

What happens to Salmonella that escape being kill by stomach acid?

A

pass into small intestine, where invasion into host cell may occur

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18
Q

Salmonella enterica serovar Typhi (S. typhi)

What is typhoid fever?

A

serious and often-fatal disease characterized by nausea, vomiting, and fever

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19
Q

Salmonella enterica serovar Typhi (S. typhi)

What disease does this cause?

A

typhoid fever

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20
Q

Salmonella enterica serovar Typhi (S. typhi)

What hosts is S. typhi pathogenic to?

A

humans only

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21
Q

Salmonella enterica serovar Typhi (S. typhi)

What is the main source of infection of S. typhi?

A

drinking contaminated water, or consumption of food that is washed or irrigated with contaminated water

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22
Q

Salmonella enterica serovar Typhi (S. typhi)

How long is the incubation period of typhoid fever?

A

week to a month after initial ingestion of bacteria

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23
Q

Salmonella enterica serovar Typhi (S. typhi)

How does the systemic infection stage of typhoid fever occur?

A

bacteria can multiply in the spleen and liver, then a large number is released into bloodstream

this stage of typhoid of fever can last 2-3 weeks

  • high fever and chills
  • flushed appearance
  • anorexia
  • convulsions
  • delirium
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24
Q

Salmonella enterica serovar Typhi (S. typhi)

How might people shed S. typhi into their feces?

A

bacteria from the liver also moves to gall bladder, where they are shed in the bile and back into intestine – eventually shed as feces

*severe ulceration of the intestine may occur – infection is likely fatal

25
Q

Salmonella enterica serovar Typhi (S. typhi)

Who are the main spreaders of typhoid fevers? How?

A

asymptomatic carriers

26
Q

Salmonella enterica serovar Typhi (S. typhi)

During an outbreak of typhoid fever, what may occur in individuals?

A
  • may become infected, but remain asymptomatic

- may recover, but become chronic carriers – bacteria persist in gall bladder and shed in feces for years

27
Q

Salmonella enterica serovar Typhimurium (S. typhimurium)

What does S. typhimurium cause in humans?

A

self-limiting gastroenteritis

  • diarrhea
  • abdominal cramps
  • vomiting
  • nausea
28
Q

What bacteria is a common cause of food-born illness?

A

S. typhimurium

29
Q

Salmonella enterica serovar Typhimurium (S. typhimurium)

How long do symptoms of infection last?

A

appear 6-24 hours after ingestion of bacteria

last up to around 7 days

may be relatively mild, or very severe

30
Q

Salmonella enterica serovar Typhimurium (S. typhimurium)

What is systemic shock caused by?

A

(in immunocompromised and elderly)

small number of S. typhimurium enters bloodstream, causing a systemic infection, leading to systemic shock – may be fatal if not treated right away with antbiotics

31
Q

Salmonella enterica serovar Typhimurium (S. typhimurium)

Does S. typhimurium produce toxins?

A

no – does not produce any of the enterotoxins that seem to be necessary for pathogenic bacteria to cause diarrhea

32
Q

Salmonella enterica serovar Typhimurium (S. typhimurium)

How do Salmonella cause the diarrhea and pain associated with salmonellosis?

A

abdominal pain is likely due to:

  • inflammatory response that results from recognition of bacterium’s LPS
  • subsequent release of cytokines, as well as that caused by the Salmonella pathogenicity island 1 (SPI1) effects
33
Q

What does Salmonella diagnosis require?

A

isolation of organisms from clinical specimens (ie. blood or stool)

34
Q

Salmonella Diagnosis – Procedure

A
  1. clinical specimen is plated onto selective and differential media
  2. identification of suspicious colonies is done by biochemical tests
  3. identification of serotype is done by antigenic analysis of O (cell wall antigen) and H (flagella antigen) using polyvalent and specific antisera
35
Q

What is the Widal test for diagnosing Salmonella infections?

A

patient’s serum is tested fro presence of antibodies against Salmonella H and O antigens

useful when facilities for culturing Salmonella bacteria are unavailable

36
Q

Widal Test – Procedure

A
  1. Salmonella H and O antigens are prepared as stained suspensions
  2. Suspensions are mixed with patient’s serum

Interpreting Results:

  • agglutination = positive test result
  • if positive reaction is observed with 20 μl of test sample, this indicates presence of clinically significant levels of corresponding antibody in patient serum
37
Q

What is the usual treatment for Salmonella?

A

nothing – infections are usually resolved within a week

38
Q

What can Salmonella be treated with?

A
  • rehydration therapy – for severe diarrhea
  • antibiotic therapy (ampicillin, gentamicin, trimethoprim, ciprofloxacin) – for infections that have spread from intestines to blood
39
Q

What is the treatment of choice for S. typhi?

A

antibiotics – chloramphenicol, ceftriaxone

40
Q

What vaccines are currently available for prevention of Salmonella infections?

A
  • whole dead bacteria vaccine (injected)
  • capsular material with Vi antigen vaccine (injected)
  • live attenuated/avirulent strain of S. typhi vaccine (oral)
41
Q

What are virulence factors of Salmonella?

A
  • adhesins
  • type I fimbriae
  • plasmid-encoded fimbriae
  • LPS
  • capsules
  • type III secretion systems
  • ability to invade and replicate inside host cells
42
Q

Where are genes that encoded Salmonella virulence factors?

A

pathogenicity islands (PAIs) in Salmonella genome

43
Q

What are pathogenicity islands (PAIs)?

A

large regions of DNA that encode clusters of genes associated with virulence

  • toxin genes
  • adhesion genes
  • invasion genes
  • etc.
44
Q

How are genes that encode Salmonella virulence factors obtained?

A

may have been acquired during evolution by HGT

are often associated with bacteriophage or prophage genes

45
Q

Where are PAIs not found?

A

in genomes of non-pathogenic members of the same or related species

46
Q

What are type III secretion systems?

A

protein structures that pathogenic bacteria can use to inject proteins into a host cell’s cytoplasm or endomembrane system

47
Q

What are Salmonella’s two type III secretion systems?

A
  • one encoded by genes in SPI1

- one encoded by genes in SPI2

48
Q

What is an injectisome?

A

type III secretion system –delivery system

type III secretion system has hollow needed that spans the plasma membrane of the host cell to inject proteins into the host cell

49
Q

SPI1

What genes does SPI1 contain?

A
  • genes associated with virulence

- genes involved in regulation of virulence genes

50
Q

SPI1

What are the inv genes?

A

responsible for:

  • disruption of normal cell function
  • promotion of membrane ruffling associated with invasion (internalization) of Salmonella by host cells
51
Q

SPI1

Protein Injection by SPI1 System – Process

A
  1. effector protein is injected
  2. triggers rearrangement of actin inside host cell
  3. results in membrane ruffling of epithelial cell
  4. formation of pseudopods engulf bacterium and internalize it inside vacuole
  5. extensive actin rearrangement in vicinity of invading bacterium
    - however, surface of host cell and actin filaments in the region return to normal
52
Q

SPI2

Protein Injection by SPI2 System – Process

A
  1. SPI2 activated after internalization by intestinal epithelial cell
  2. SPI2 injects several protein effectors into cytoplasm and endomembrane system of the cell
    - proteins alter structure of membrane to maintain vacuole, and prevent fusion of lysosomes with vacuole
  3. Salmonella-containing vacuole (SCV) gradullay matures through interactions with host endocytic pathway into a specialized compartment
  4. Salmonella replicate in compartment
  5. as bacteria replicate, vacuole sprouts thin filaments that stretch out from the walls of the surface
53
Q

Is SPI2 essential for virulence of bacteria? Why?

A

yes – mutant strains of Salmonella are not able to maintain structure of SCV, and are released into cytoplasm of host cell where they are quickly killed

54
Q

Inside the Intestinal Epithelium

A

S. typhimurium uses specific set of effector proteins, which are delivered into cells via its SPI1 injectisome to activate responses such as NF-κB signalling pathways, which closely mimic those induced by the stimulation of innate immune receptors such as TLR

therefore, intestinal epithelial cells can produce cytokines and chemokines to recruit neutrophils to infected area

neutrophils produce prostaglandin that acts on intestinal epithelial cell to increase internal concentration of cAMP

increased levels of cAMP cause increase in secretion of Cl­– ions and Na+ ions into lumen of intestine

as concentration of NaCl increases in lumen of intestine, water is lost from tissues into lumen, resulting in diarrhea

infection is eventually cleared from host by combined action of diarrhea and shedding of infected epithelial cells

55
Q

What is SPI1 secretion system required for?

A

invasion into host tissues

56
Q

What is SPI2 secretion system required for?

A

survival inside intestinal epithelial cells

57
Q

SP1 secretion system can activate signalling pathways that produce what?

A

pro-inflammatory cytokines and chemokines that recruit neutrophils to site of infection

58
Q

What does the production of prostaglandin by neutrophils do?

A

increases internal concentration of cAMP, resulting in secretion of Cl- ions and Na+ ions into lumen of intestine

59
Q

What triggers diarrhea associated with Salmonella infections?

A

host’s immune response

+ MICB 202 Final (20 decks)

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