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Infectious Disease > Prelim 1 > Flashcards

Prelim 1 Flashcards

1
Q

What is a pathogen? Pathogen centric definition

A

You might be more used to thinking about pathogens as microorganisms that make you sick.

Historically, this was an important step forwards in science, the creation of the germ theory of disease, the recognition that organisms cause disease, not other theories liek “miasma”

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2
Q

Koch’s Postulates

A
  1. You must have a diseased organism. The suspected causative agent (microbe) must be absent from all healthy organisms but present in all diseased organisms
  2. The causative agent must be isolated from the diseased organism and grown in pure culture
  3. The cultured agent must cause the same disease when inoculated into a healthy, susceptible organism
  4. The same causative agent must then be reisolated from the inoculated, diseased organism.
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3
Q

Is a microbe always a pathogen?

A
  • Not all strains of a given microbe will cause disease (not all cholera strains have toxin genes)
  • Not all individuals will develop an infection or symptoms
    (some individuals with COVID-19 may remain asymptomatic)
  • Some microbes may only cause disease in specific circumstances (immunocompromised individuals may be more susceptible to infection)
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4
Q

Molecular Koch’s Postulates

A
  • The phenotype or property that is under investigation should be associated with pathogenic members of a genus or pathogenic strains of a specific species
  • Specific inactivation of the gene or genes that are associated with the suspected virulence trait should lead to a measurable loss in pathogenicity or virulence
  • Reversion or allelic replacement of the mutated gene should lead to restoration of pathogenicity
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5
Q

Mutualism

A
  • When both partners benefit from an interaction. For example, a host and beneficial symbiont
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6
Q

Commensalism

A

When two organisms live together with negligible/positive effects on each other

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7
Q

Parasitism

A

When one partner benefits at a cost to the other

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8
Q

Disease

A

A clinical definition where the host has suffered damage due to an interaction

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9
Q

Cycle for Interactions of microbe and host

A
  • Contact host
  • Attachment/Recognition –> Elimination (clearance)
  • Infection (pathogen begins to establish)
  • Colonization (Dead end, no transmission)
  • Exist host (shedding, acquisition by vector) –> vector, fomites, contaminated water reservoir host (survival outside host)
  • Direct transmission
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10
Q

Damage

A

Disruption of the normal functioning in a host, can be at any level from molecular to cellular, or from tissue to the whole organism

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11
Q

Virulence

A

A relative measure of how much damage pathogen causes

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12
Q

Virulence factors

A

The component of a microbe that damages a host

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13
Q

Damage-Response Frameworks for Pathogens

A
  • Microbial pathogenesis is an outcome of an interaction between a host and microorganism
  • The host-relevant outcome of the host-microorganism interaction is determined by the amount of damage to the host
  • Host damage can result from microbial factors and/or the host response
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14
Q

Draw all 9 classes of the Damage Response Framework

A

Draw

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15
Q

Important points of pathogens

A
  • A microbe or parasite that causes disease or damage to a host
  • Definition focus on what happens to the host, how much damage the host suffers
  • Being pathogen is always context dependent
    • Depends on factors such as the specific host or pathogen, as well the environment
  • The reason a pathogen causes damage can be direct or indirect, from the pathogen or from the or from the host response to the pathogen
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16
Q

Cholera Pathology

A
  • Infection from contaminated water or food - large doses are required
  • Colonization leads to watery diarrhea, electrolyte loss, and severe dehydration, ~50% mortality if untreated
  • Rehydration therapy is generally effective, not always available
  • Mortality is higher with babies and children, pregnant women
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17
Q

Origins of Cholera Pandemic

A
  • Cholera is caused by the marine bacterium Vibrio cholerae
  • V. cholerae is commensal on copepods (zooplankton) in estuarine/marine environments
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18
Q

Three virulence factors in the 7th cholera pandemic

A

1) Cholera toxin genes, (ctxAB) in CTXo phage genome
2) Toxin coregulated pilus (TCP) in Vibrio pathogenicity island 1 (VP-1)
3) Additional pathogenicity islands, Vibrio seve th pandemic 1 and 2

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19
Q

How does the bacteriophage CTXo change the virbrio cholera ?

A
  • A bacteriophage contains the toxin gene ctxAB, and starts by attaching to the host and injecting the Vibrio Cholera DNA.
  • Phage DNA circularizes and enters lytic cycle or lysogenic cycle
  • LYTIC CYCLE: New phage DNA and proteins are synthesized and assembled into virions
  • Cell lyses, releasing phage virions
  • LYSOGENIC CYCLE: Phage DNA integrates within the bacterial chromosome by recombination becoming a prophage
  • Lysogenic bacterium produces normally
  • Occasionally, the prophage may ex
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20
Q

Which infection from cholera is more powerful?

A

Shed cells from infected people are 10-100 times more infective than environmental cells. They are present highly in the water

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21
Q

What is the bacteriophage name?

A

CTXo
and the toxin is ctxAB

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22
Q

Can CTXO attach to all cholerae cells?

A

It can only attach to the TCP (Toxin co-regulated pili, pili are similar to flagellum) of the bacterial cell to initiate infection

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23
Q

Where does V. Cholerae attach?

A

To intestinal villi with the TCP (toxin coregulation pilus)

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24
Q

Summary of cholera generation:

A
  • Bacteriophage, CTXo attaches the TCP of certain V. Cholerae bacteria to either make more viral dna/protein or to recombine its toxin gene, ctxAB into the bacteria’s genome.
  • Bacteria is gonna attach to the intestinal vila using its TCP
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25
Q

How are V. Cholerae strains grouped?

A
  • They’re grouped by serotype (sharing similar cell surface antigens that interact with the immune system)
  • And biotype (strains that act biologically similarly)

Notice that these vary in whether they make toxin and also if they tend to show epidemic spread

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26
Q

Seventh Cholera Pandemic (El Tor)

A
  • Began in Indonesia in 1961, has since spread worldwide
  • These strains are closely related to strains that are pathogenic (do not cause disease symptoms) or that did not effectively spread between people
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27
Q

How did the 7th pandemic strains emerge?

A
  • Stage 1: El Tor strain diverges and migrates to the Middle East (starts in Bengal)
  • Stages 2 and 3: Gain of TCP, Gain of classical ctx phage
  • Dispersal to Indonesia
  • Gain of VSP 1 and VSP 2
  • 7th pandemic began, spread to the rest of the world
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28
Q

What is genomic epidemiology?

A
  • Can refer to any use of genomic information to study epidemiology
  • Here, we specifically use the genomic information to track pathogen spread or emergence
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29
Q

Shotgun sequencing

A

Shotgun sequencing is a laboratory technique for determining the order of DNA sequence of an organism’s genome

30
Q

Next-generation sequencing

A

The technology is used to determine the order of nucleotides in entire genomes or targeted regions of DNA or RNA.

31
Q

Reads

A

Short chunks of DNA sequence

32
Q

Assembled and aligned

A

Reads can either be assembled to reconstruct the genome or aligned to a reference genome

33
Q

Contigs

A

Chunks of the genome, used to study genes or sequence

34
Q

What does alignment help you do?

A

Find where your sequence differs from the reference sequence, these are called variants or single nucleotide polymorphisms (SNPs)

35
Q

How do you make a phylogeny?

A

First, you need the same sequence from all of your organisms of interest
Then you align the sequences against each other
Then you use a program to reconstruct a phylogeny

36
Q

Bootstrap values below ___ indicate low confidence

A

80%

37
Q

Limitations of phylogenies

A
  • Low support values at nodes
  • Short branches
  • Too few taxa
38
Q

What are host defenses?

A

Responses by an organism to prevent infection by microbes, or slow or stop growth (and therefore damage) of microbes in the body

39
Q

Non-immunological defenses

A
  • Hygiene adaptations
  • Avoiding spoiled foods
  • Behaviors

Symbiont mediated by the gut microbiome

40
Q

Immune response overview

A
  • Reactions by an organism against comounds that are recognized as foreign
    Aimed at defending againts microbes but could also be components of microbes, foreign substances, or even itself
  • Innate and adaptive immune system
41
Q

Innate Immunity

A
  • Always in place, can respond to infection but does not need to be activated
  • Generalized, not specific to certain pathogens
  • Often described as the first line of defense because it is active when pathogens first infect

1) Barriers
2) Certain immune cells
3) Components of blood that will cause inflammation
4) Chemicals that communicate with the adaptive immune system

42
Q

Barriers

A

Prevent entry into the body
Chemical and physical

ex, lysozyme in tears, mucus, skin, stomach

43
Q

Inflammation

A

Induced by the complement system and induces inflammation
Increased blood flow and recruitment of more immune cells

44
Q

Adaptive Immunity

A

Induced by the presence of pathogens
Highly specific, recognizes specific anitgens for specific pathogens
Creates immune memory, so that responses can be quicker for a second exposure

1) Immune cells called lymphocytes
2) Antibodies, which recognize antigens
3) Functions to find and display antigens (MHC I and II)

45
Q

What do antibodies do?

A

Block extracellular pathogens by neutralizing them

46
Q

What do APCs do?

A

Cells present antigens using MHC molecules to T cells

47
Q

Humoral responses

A

Antibodies neutralizing microbes, phagocytosis, complement activation

48
Q

Septicemia

A

Damage is caused by an overwhelming immune response, not the microbes themselves

49
Q

What are examples of how the immune system can misclassify things as antigens?

A

Allergies
Autoimmune diseases

50
Q

Are host defenses just for vertebrates, animals or multicellular organisms?

A

Host defenses are more broad and varied than just the vertebrate adaptive immune response
Most organisms have innate immunity, which recognizes broad features of pathogens
But non-vertebrates also have acquired immunity, which is specific to a pathogen and also leads to immune memory

51
Q

Acquired Immunity

A
  • Non vertebrates have adaptive immunity because they have “custom fit immunity”
  • Not inherited, requires prior exposure during an individual organism’s life
  • Not always on, triggered by exposure
52
Q

Bacterial defense responses

A
  • Restriction modification systems
  • Restriction enzymes recognize viral DNA based on methylation patterns and degrade it
  • Innate response which recognized self vs. non self DNA
  • Bacteria can store viral sequences in a CRISPR array
  • Array sequences are targeted for degradation whern they are encountered again
  • This gives bacteria transgenerational immune memory !
53
Q

How are antibiotics bad for the gut microbiome?

A

They can lead to dysbiosis which changes the colonies that live in our gut

54
Q

C. diff infection

A
  • Gram-positive, spore forming bacterium
  • Common, present in 2-5 percent of adults
  • Can cause disease in certain contexts
55
Q

How does the environment impact pathogens?

A

The environment can be a reservoir for pathogens, but also for genes that increase pathogenicity

56
Q

Bacteria ecology and disease

A
  • Many bacteria that can be human pathogens also live in environments and interact with other organisms
  • These interactions may increase the abundance of pathogens in environmental reservoirs, or many influence the evolution of the bacteria in ways that increase pathogenicity
57
Q

Abiotic Factors that Induce Pathogen Abundance

A
  • V.cholerae in water environments is influenced by temperature and salinity
  • Factors like rainfall also induce spread
  • Multiple studies have found links between cholera and El Nino events
58
Q

The environment can facilitate HGT

A
  • Bacteria can experience high levels of horizontal gene transfer (HGT), the movement of genes between bacterial lineages
  • Modes of HGT include
  • Plasmids (small circular DNA molecules found in bacteria that are separate from chromosomal DNA and replicate independently) (conjugation: transfer of genetic material through direct contact)
  • Movement by phage (transduction: virus transfers genetic material from one virus to another)
  • The uptake of naked DNA (natural competence- take up random dna and insert it into their genome)
59
Q

How can non-human host infleuence pathogen evolution?

A

Biofilms and competence

60
Q

What is the resistome

A

Antibiotic resistant genes

61
Q

What is an antibiotic?

A

Chemicals that are toxic to bacteria. They may not kill bacteria, just stop them from growing

62
Q

Where do antibiotics come from?

A

Most are derived from microbes, especially bacteria. This is because they wanted to kill competitors

63
Q

Where do nearly all antibiotics for human and animal use come from?

A

Soil Actinobacteria but some can also come from steptomyce

64
Q

What do anitbiotics often target?

A

Cell walls or membranes

65
Q

Fitness

A

Refers to the organism’s ability to survive and reproduce

66
Q

Selection

A

The process by which certain traits become more common because they improve fitness or the ability to survive

67
Q

4 main mechanisms of anitbiotic resistance

A
  • Keep antibiotics out (cell walls)
  • Change the molecule that antibiotics target
  • If they get in, remove them (efflux pump)
  • Degrade them (B-lactams)
68
Q

What mechanism comes in handy when talking about antibiotic resistance?

A

Degrading them/Removing

69
Q

ARGs

A

They can be specific like how B lactams target antibiotics to degrade
They can be general how an efflux pump removes any antibiotics

70
Q

What are the benefits and harms to changing the molecules that antibiotics are targeting?

A
  • Spontaneous resistance comes from mutations in cells
  • However, these mutations will have a fitness cost
  • Can provide a fitness benefit under some conditions and be selected for
71
Q

How do we know if something is antibiotic resistant?

A

Can calculate Minimum Inhibitory Concentration (MIC)
- Detect zones of inhibition around the antibiotic

Infectious Disease (3 decks)

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