Human Microbiome

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What is the Microbiome?

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1

What is the Microbiome?

Collection of genomes of all the microorganisms found in a particular environment

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What is the Human Microbiome?

Collective genomes of the microbes (composed of bacteria, bacteriophage, fungi, protozoa, & viruses) that live inside/on the human body.

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3

What is the collection of microbial genomes that contribute to the broader genetic portrait?

Metagenome

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4

"The human body is a Supraorganism," means what?

Collection of human & microbial cells & genes = blend of human & microbial traits

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5

What is the difference between Commensal & Mutualistic relationships?

Commensal coexists without harming humans & Mutualistic means they both benefit

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6

What is the Human microbiome project (HMP)?

Founded in 2007 by the NIH, a research initiative to improve understanding of human microbiota for health & disease by characterizing the human microbiome & analyze its role in human health & disease

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7

How did the HMP go about the project?

Sequencing the genome of the human microbiota specifically in the skin, mouth, nose, digestive tract, & vagina

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8

What is the majority of Normal flora?

Bacteria (>200)

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9

Other names for the Normal flora?

Normal microflora, commensals, & indigenous microbiota

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10

What does the makeup of the Normal flora depend on?

Genetics, age, sex, stress, diet, antibiotics/drugs, & environmental conditions

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11

What are major differences between the 2 types of Normal flora, resident & transient?

Resident - Fixed, established at a given age & area, & can reestablish if disturbed. Transient - Non-pathogenic/potentially pathogenic, inhibits skin or mucous membranes for hours-weeks, doesn't produce disease, & derived from the environment

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12

What are some reasons that Transient flora microbes are temporary?

Can be washed from external surfaces by bathing, not able to compete with resident microbes &can be killed by their substances, can't survive in acidic/alkaline conditions, & may be flushed away by bodily secretions

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13

Examples of anatomical sites involved the Normal flora?

Skin, eyes (conjunctiva), nose (resp. tract), oral cavity, ears, genitourinary tract, & alimentary canal

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14

What are some commensal organisms that help to breakdown/destroy debris on the skin?

Propionibacterium acne, staphylococcus epidermidis, staphylococcus aureus, diphtheroids, candida, mycobacterium smegmatis, etc.

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15

Examples of Normal flora of the conjunctiva:

Staphylococcus epidermidis, commensol neisseria, propoinibacterium acnes, etc.

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Examples of Normal flora of the oral cavity:

Streptococcus viridans, lactobacilli, staphylococcus aureus, trichomonas, etc.

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17

Examples of Normal flora of the respiratory tract (nasal cavity):

Staphylococcus epidermidis, corynebacteria spp, staphylococcus aureus, etc.

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18

Examples of Normal flora of the respiratory tract (nasopharynx):

Non-hemolytic streptococci, alpha-hemolytic streptococci, streptococcus pneumoniae, neisseria meningitidis, etc.

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19

Examples of Normal flora of the respiratory tract (lower resp. tract):

Usually sterile, but can become infected from nasopharynx pathogens such as H. influenza or S. pneumoniae

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20

What intestinal bacteria accounts for 90% of the total intestinal bacteria?

Bifidobacteria

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21

The other 10% of bacteria in breast fed infants?

Enterobacteriaceae, enterococci, bacteroides, staphylococci, lactobacilli, & clostridia

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22

When breast fed infants switch over to bottle feeding Bifidobacteria is followed with?

Bacteroides, enterococci, lactobacilli, clostridia, & enterics

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23

In the esophagus & stomach what bacteria is present <10% of the time?

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24

In the small bowel area (duodenum, jejunum, & ileum) what bacterias are present <10% of the time?

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25

In the large bowel area what bacterias are present <10% of the time?

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26

What are the 6 benefits of the Normal flora?

  1. Synthesize & excrete vitamins. 2. Prevent colonization by pathogens by competing for attachment sites or essential nutrients. 3. Antagonize other bacteria through prod. of substances that kill/inhibit non-indigenous species. 4. Stim. prod. of cross-reactive antibodies. 5. Stim. development of immune system in newborns. 6. Stop/suppress entry of pathogens

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27

What are some harmful effects of Normal flora?

The immunocompromised normal flora can overgrow = pathogenic. Dental caries, plaque, gingivitis, etc. Dental manipulation - oral streptococci can cause rheumatic fever. When substances that can be mistaken are ingested the Normal flora may cause confusion when diagnosing

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28

What are the sterile tissues within a human?

Blood, brain, muscle, & CSF

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29

What is an Opportunistic pathogen?

Infectious pathogen that's normally commensal but can cause disease when the host's resistance is altered. Low resistance can be caused bc of HIV, genetic factors, leukopenia, or aging

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30

Where are Opportunistic pathogens mostly found?

Hospital settings

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31

What can cause disturbance of the host immunity?

Administering immunosuppressants, advanced HIV, chemotherapy, damage of the skin (surgeries), or antibiotic intake disrupting the normal flora in the body

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32

What can influence an opportunistic infection?

Impaired immunity, surgeries & instrumentation, broad spectrum antibiotic administration, or damage of an organ or system

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33

What is an HIV patient likely to develop during the advanced stages?

Kaposi's sarcoma

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34

Opportunistic pathogens have a high percentage of death in patients with which diseases?

AIDS & cancer patients

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35

Which Opportunistic infections are fungus & where are they found?

Candidiasis - mouth, throat, foot, & vagina. Cryptococcosis - brain & spinal cord. Pneumocystis pneumonia - lungs.

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36

Which Opportunistic infections are viruses & where are they found?

Cytomegalovirus - eyes, lungs, brains, & guts. PML - brain.

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37

Which Opportunistic infections are parasites & where are they found?

Cryptosporidiosis - gut. Toxoplasmosis - brain.

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38

Which Opportunistic infections are bacterium & where are they found?

Mycobacterium avium complex - gut, lung, & skin

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39

Which Opportunistic infections are bacteria & where are they found?

Mycobacterium tuberculosis - lung, heart, liver, & brain

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40

What are the differences between a True pathogen vs a Opportunistic pathogen?

True pathogens cause disease in healthy individuals & asso. with specific & reasonable diseases while opportunistic pathogens cause disease in immunocompromised & gain access/injury to sterile regions

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41

Examples of True pathogens:

Salmonella typhi, yersinia pestis, haemophilus influenzae, bordatella pertussis, shigella dysentriae, klebsiella pneumoniae, etc.

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42

Examples of Opportunistic pathogens:

Pseudomonas aeruginosa - candida, acinetobacter baumanii, proteus vulgaris, enterobacter, etc.

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43

What must a pathogenic microbe do to survive a host?

Attach to host cells for colonization, evade host's innate & adaptive immune defenses to persist, obtain nutrients essential for growth to multiply, disseminate/spread within a host & other hosts (critical for species survival), & produce symptoms of disease in the host in order to be pathogenic

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44

What are virulence factors?

Components or structure of microorganism that helps in establishment of disease or infection

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45

How is infection established & not eliminated?

Virulence factors must overcome host's defense mechanisms

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46

What are some virulence factors?

Attachment factors/adhesins, anti-phagocytic factors, spreading factors & enzymes, & toxins = exo/endotoxins

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47

What is an important antiphagocytic factor for some bacteria?

Capsules

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48

What is the host defense mechanism that prevents spreading of microorganisms?

Blood clotting

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49

What is Leukocidin?

Pore forming cytotoxin that attacks WBCs by targeting phagocytes, NKCs, dendritic cells, & T lymphocytes

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50

What does Leukocidin prevent?

Bacteria from phagocytosis by releasing & rupturing lysosomes. Ex: S. aureus - LukED & leukocidin AB

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51

What is Haemolysin?

A cytotoxic protein that causes lysis of RBCs by disturbing cell membrane & liberates hemoglobin

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52

What is Alpha hemolytic streptococci?

Secretes hemolysins that cause the incomplete lysis of RBCs

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53

What is Beta hemolytic streptococci?

Secretes hemolysins that cause the complete lysis of RBCs

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54

What does the Fibrin coat do?

Protect the bacterium from phagocytosis & isolate it from other defenses of the host. Makes bacteria more virulent

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55

How are Hyaluronidase's important in regards to drugs?

Mixed with the drug to help spread the drug throughout a body tissue

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56

What is the difference between host Collagenases & bacterial Collagenases?

Host collagenases destroy extracellular structures in the pathogenesis of bacteria. Bacterial collagenases allow bacteria to breakdown protein to invade the host.

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57

Collagenases are association with what disease?

Clostridium perfrinogens - gas gangrene

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58

In the Infection process what does bacteria do?

Bacteria invade the tissues, grow, & reproduce

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59

In the Intoxication process what does bacteria do?

Bacteria produce certain potent effective toxins which cause disease & symptoms of disease

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60

What is Toxemia?

State caused by toxins entering the bloodstream of the host

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61

What are the Endotoxins?

Lipopolysaccharides (LPS)

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62

What are the Exotoxins?

AB toxins, specific host site exotoxins, membrane disrupting exotoxins, & super antigen

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63

What are some significant features of Exotoxins?

Some gram pos & neg, protein location = secreted from cell & gene location = plasmid or bacteriophage, high toxicity, highly antigenic (antitoxins), vaccine from toxoids, & heat labile

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64

Examples of Exotoxins:

Toxins prod. by S. aureus, bacillus cereus, streptococcus pyogenes, b. anthracis, & c. tetani

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65

What are some significant features of Endotoxins?

Most gram neg & listeria, protein location = part of cell/LPS that fragments off & gene location = bacterial chromosomes, low toxicity, poorly antigenic, no vaccine, & heat stable

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66

Examples of Endotoxins:

Gram neg pathogens such as Escherichia coli, salmonella, shigella, pseudomonas, & neisseria

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67

What is the exotoxin AB toxin?

B portion binds to the receptors & A portion can cause toxicity

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68

What is the exotoxin Specific host site exotoxin?

Type of AB toxin that affects the specific regions of the host such as neurotoxins affects CNS, enterotoxins affects intestines, & general cells or tissues are affected by cytotoxins

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69

What is the exotoxin Membrane disrupting toxin?

Type of AB toxin, but they act together by disrupting host cell membranes e.g., hemolysis, phospholipases

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70

What is the exotoxin Superantigen?

Unusual bacterial toxins that triggers T cells (T4 Lymphocytes) to release cytokines - bind to surface of target cell but don't enter

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71

How do AB toxins enter the cell?

B subunit binds to the target cell & allows A subunit to enter the cell

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72

What occurs once Conventional antigens are engulfed by APCs?

They're degraded into epitopes, bind to peptide groove of MHC-II molecules, & are put on surface of the APC

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73

When Superantigens bind outside MHC-II & activate T4-Lymphocytes what is the result?

Secretion of excessive amounts of IL-2 & activation of self-reactive T-Lymphocytes

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74

Increased IL-2 in the blood can cause what?

Fever, nausea, vomitting, diarrhea, & malaise. Excess stim. leads to prod. of inflammatory cytokines like TNF-alpha, IL-1, inflammatory chemokines like IL-8, & platelet-activating factor (PAF) = shock & multiple organ system failure

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75

Examples of bacterial Superantigens:

Staphylococcal enterotoxins - food poisoning. Staphylococcal toxic shock toxin (TSST-1) - toxic shock syndrome. Staphylococcal exfoliating toxins - scalded skin syndrome. Staphylococcal pyrogenic exotoxins (exotoxin A & B) - shock.

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76

What is Toxic shock syndrome (TSST)?

Toxins produced by Staphylococcal aureus. Asso. with cuts or burns on skin, recent surgery, using contraceptive sponges, diaphragms, tampons/menstrual cups, or a viral infection like the flu or chickenpox

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77

Symptoms & complications of TSST:

High fever, vomiting or diarrhea, redness around eyes & vagina, sunburn rash, low bp, headache, & muscle pain. Complications = shock, renal failure, or death

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78

Difference between Reinfection & superinfection:

Reinfection is infection by the same organism in a host after recovery while superinfection is before recovery

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79

What is a Focal infection?

Infection at localized site prod. general effects

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80

What is a Nosocomial infection?

Infections acquired within a hospital

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81

What is an Iatrogenic infection?

State of health or adverse effect caused by medical treatment

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82

What are the differences between Exogenous infections & endogenous infections?

Exo infections are pathogens enter the body from outside environment via contaminated device, healthcare worker, surface, or other vector. Endo infections are pathogens present on/in host itself without prior symptoms

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83

Examples of Exogenous infections:

Dysentery, cholera, influenza, & covid-19

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84

Examples of Endogenous infections:

Periodontal diseases, aspiration pneumonitis, & bacterial vaginosis

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