Booklet 7: Medical Microbiology Flashcards
Define human microbiome
The collection of all the microorganisms living in association with the human body (microflora, microbiota)
Describe the human microbiome
# of human cells in body = 10^13 # of microorganisms in body = 10^14 # of genes in the human genome = 20,000 # of genes in the micro biome = 20,000,000
When does colonization occur?
Immediately after birth
T or F: the diversity of bacterial species present is the exact same between each individual
False: it varies quite a lot
Where does microbiota live?
-every externally exposed area of the body is colonized by bacteria
T or F: internal tissues that have no exposure to the external environment should not have any microbes
True
What are examples of externally exposed areas of the body that would have bacteria?
- skin
- mucous membranes
What are examples of internal tissues that should be free of bacteria?
- blood
- muscles
- organs
What is the purpose of having bacteria on your body?
-produce beneficial products
-inhibit the growth of some pathogens
Ex. - Lactobacillus acidophilus protects the female reproductive tract.
What are the 3 types of microenvironments in which bacteria live?
- dry skin
- moist skin
- sebaceous skin
Give an example of dry skin, moist skin, and sebaceous skin
Dry - forearms, hands
Moist - armpits, nostrils
Sebaceous - oily skin on nose, on the upper chest and back
Describe the bacteria on dry skin
- high numbers of Betaproteobacteria
- second highest is Corynebacteria
-Most bacteria that live on dry skin are harmless, but some do cause skin infections such as Corynebacterium diphtheria which can cause non-healing ulcers of the skin
Describe the bacteria on moist skin
- high numbers of corynebacteria and staphylococci
- most are harmless commensals (staph epidermis)
- some are important pathogens (staph aureus)
What can staph aureus cause on the skin?
boils, abscesses, or wound infections
Describe the bacteria on sebaceous skin
- High numbers of propionibacteria
- Propionibacteria are anaerobic actinobacteria that produce propionic acid as an end product of fermentation
- An example is propionibacterium acnes which causes acne on the skin
- It lives in hair follicles and eats sebum (oil secreted by the skin)
- Overgrowth of this can cause inflammation
What antimicrobial enzymes are present in the saliva and mouth?
Lysozyme
Lactoperoxidase
Neisseria mucosa
Streptococcus mutans
List some points about Streptococcus mutans
- lives in the oral cavity
- aerotolerant anaerobe
- produces a sticky slime layer
- produces lactic acid as an end product of fermentation
- degrades tooth enamel
- can lead to inflammation along the gum line (gingivitis)
What is an example of bacteria that lives in the stomach?
Helicobacter pylori
List some points about helicobacter pylori
- colonizes surface of membrane
- protected from the stomach acid by mucous
- cause of stomach ulcers
- has virulence factors:
- endotoxin - kills cells in the membrane
- exotoxin - triggers inflammation
Can helicobacter pylori be treated with antibiotics? If so, which one?
Yes - tetracycline
In the small intestine: As pH becomes more neutral, bacteria numbers ________ ?
Increase
Give an example of bacteria in the small intestine.
Enterococcus (Gram positive lactic acid bacteria)
List 4 points about Enterococcus
- opportunistic pathogen
- frequent cause of nosocomial infections
- develop antibiotic resistance readily
- spread resistance genes onto other gram positive bacteria (horizontal gene transfer)
What is the difference between vertical and horizontal gene transfer?
Vertical - transfer of genes from parental generation to offspring
Horizontal - transfer of genes between two organisms
What are the pH’s in the stomach, small intestine, and large intestine?
stomach - low (acidic)
small intestine - an area of rapidly changing pH from acidic to neutral
large intestine - neutral
Why are they so many microbes in the large intestine?
Because there is approximately 10^11 cells/g of feces.
What is an example of bacteria that lives in the large intestine?
E. coli
List some points about E. coli living in the large intestine
- most strains living in the large intestine are non-pathogenic
- may stimulate the immune system
- produce vitamine K
Although E. coli is the most common example of bacteria living in the large intestine, 16S rRNA shows that E.coli probably makes up less than 1% of the bacteria in the large intestine. So what other types of bacteria live in the large intestine?
Bacteroids
Clostridium
- they play an important role in digestion
Some people also have methanogens which may play a role in obesity.
What did studies show when normal mice were compared to germ-free mice?
Germ free mice had 40% less body fat. When the germ free mice were inoculated with microbes from the healthy mouse intestine, they quickly gained weight.
What was the result when the microbiomes were compared between the normal weight mice and genetically obese mice? And what does this suggest?
Obese mice had fewer Bacteroidetes, more Firmicutes, and way more methanogens.
This suggests that methanogens use up H2 which promotes bacterial fermentation which makes nutrients available to the host.
So we know that changing the microbiota of the large intestine can affect human health. What is an example of something that could change the microbiota of the large intestine?
Oral antibiotics.
What happens with antibiotic associated colitis? Also describe the treatment possibilities.
- C. difficile grows
- Inflammation of colon
Treatment
- further antibiotics
- probiotics
- transpoosition (fecal transplant)
What bacteria are present in the upper respiratory tract?
- staphylococci
- streptococci
- corynebacteria
Some people have pathogens among their normal microflora. What are examples of this?
- carriers of a disease
- staph aureus
Are there bacteria in the lower respiratory tract?
No.
What is present in the lower respiratory tract?
Mucous, lysozyme, ciliated cells, secretory IgA, phagocytes
Genitourinary tract is composed of the upper urinary tract (kidneys and bladder) and the urethra. What bacteria are present in these areas?
Upper urinary tract - normally free of microorganisms
Urethra - has some gram negative bacteria
What can happen when members of the normal microbiota present in the urethra move to the upper urinary tract?
They can act as opportunistic pathogens.
E. coli is one of the most common causes of urinary tract infections.
What healthy bacteria is present in the female reproductive tract? Explain why it is healthy.
Lactobacillus acidophilus - in the vagina produces lactic acid from glycogen. It lowers the pH and prevents growth of microbes.
What can happen if normal microbiota is disturbed in the female reproductive tract?
Ex. lactobacilli killed by antibiotics
Yeasts can overgrow and cause yeast infections
Define: infection
Growth of microbes that are not normally present in the host (regardless of whether or not the host is harmed)
Define: disease
Damage or injury that impairs regular host functions
Define: pathogen
A microbe that is able to cause disease
Define: opportunistic pathogen
Give 2 examples and explain how they are opportunistic.
A microbe that causes disease only in the absence of normal host resistance.
Examples:
- streptococcus pneumoniae - causes pneumonia in immunocompromised patients
- E. coli - causes urinary tract infections when bacteria from faces are moved into the urethra
What does LD50 mean?
It is the dose required to kill 50% of the infected population. (lethal dose)
What does ID50 mean?
It is the does required to infect 50% of the population. (infectious dose)
Define: pathogenicity
The ability to cause disease
Define: virulence
-The severity of the disease that is caused. -(Often given as an LD50 value)
What is the LD50 dose for streptococcus pneumoniae?
LD50 = 50 cells
What is the LD50 dose for salmonella enteric
LD50 = 5000 cells
Define: pathogenesis
The process by which a disease develops. (Steps that lead to an infection and tissue damage).
Define: virulence factors
Genetically encoded traits that contribute to a pathogen’s ability to cause disease.
Define: adherence
The ability of a pathogen to stick to a surface and begin colonization.
What are 2 examples of non-covalent adherence factors?
- capsules
- slime layers
Another example of an adherence factor are adhesins. What are adhesins?
Specific surface molecules that allow selective adherence to particular cell types.
Give at least 1 example of an adhesin.
There are 2 possible answers
- Strains of enterotoxigenic E. coli produce fimbriae and can adhere specifically to the cells in the small intestine.
- Neisseria gonorrhoea produce fimbriae that allow it to attach to mucosal epithelial cells.
T or F: All pathogens can colonize and grow on the surface of tissues
False - some pathogens need to invade the tissue
Define: Invasiveness
The ability of a pathogen to enter into host cells of spread through tissues
List 3 virulence factors that promote invasiveness
- Siderophores
- Exoenzymes
- Invasins
What are siderophores?
- Iron binding molecules
- Host proteins transferrin and lactoferrin sequester iron, making it unavailable for microorganisms (limits the growth of the invaders)
- Siderophores rip iron out of the tissues to be used by bacteria
What are exoenzymes?
-Excreted by bacteria to degrade host tissues
What are the 5 types of exoenzymes?
- Hyaluronidase
- Collagenase
- Proteases, nucleases, and lipases
- Fibrinolysin
- Coagulase
What does hyaluronidase do?
It hydrolyzes hyaluronic acid (cement that holds animal cells together). It allows the pathogen to spread between cells
What does collagenase do?
Degrades collagen (structural component of connective tissue). It allows the pathogen to spread between cells.
What do proteases, nucleases, and lipases do?
Degrade host macromolecules
What does fibrinolysin do?
Dissolves fibrin clots.
Ex. Streptococcus progenies makes streptokinase
What does coagulase do?
Induces fibrin clots.
Ex. Staph aureus produces coagulase to protect it from phagocytes. (Keeps staph infections localized).
What are invasins?
Proteins that allow bacteria to invade and enter directly into host cells.
What is an example of an invasin?
Listeria monocytogenes.
-Non-lactic acid, non-spore forming psychrotolerant member of the Firmicutes.
Where can Listeria monocytogenes be found?
In unpasteurized dairy products, improperly packaged processed meats.
What does Listeria monocytogenes do to the body?
- It produces invasions that promote phagocytosis by macrophages.
- It hijacks the cytoskeleton to escape the phagolysosome.
- It spreads from cell to cell avoiding a normal humoral immune response.
T or F: all pathogens remain localized at the site of the infection
False - some have the capability to spread
Define: bacteremia
Bacteria in the blood (Can be carried to different organs and tissues)
Define: septicemia
Bacteria multiplying in the blood (A blood borne systemic infection)
What can septicemia lead to?
- Sepsis (widespread systemic inflammation)
- Septic Shock (can be caused by gram negative bacteria or gram positives such as staphylococci or enterococci)
What are exotoxins and what do they do?
- They are proteins released by growing bacteria.
- They inhibit host cell function or simply kill the host cells.
- They can be extremely toxic
- Usually heat labile.
What is an example of an exotoxin?
Bacillus anthracis
What are the 3 categories of exotoxins?
- Cytoxins
- AB toxins
- Superantigens
What do cytotoxins do?
- They disrupt cytoplasmic membrane integrity.
- Cell lysis and death.
What are the 3 types of cytotoxins?
- Hemolysins
- Lecithinase or Phospholipase
- Leukocidins
What do hemolysins do and what is an example?
They lyse many cells (not just red blood cells).
Ex. Streptococcus pyogenes
- Produces streptolysin which attacks sterols in the membrane
What do lecithinase of phospholipase do? What is an example?
They dissolve membrane lipids.
Ex. Clostridium perfringens
-alpha toxin (gas gangrene)
What do leukocidins do? Example?
They destroy white blood cells.
Ex. Staph aureus (staphylococcal alpha toxin)
- Toxin subunits insert into the membrane and oligomerize to form a heptamer
What is a heptamer?
A membrane spanning pore made of 7 pieces. Cell contents leak out through the heptameter and the cell dies.
Describe AB toxins and give an example.
- Two subunits: Active subunit and Binding subunit
- Ex. diphtheria toxin (interferes with protein synthesis)
- Subunit B specifically binds to a protein on animal cells
- Subunit A then moves across the membrane
Where is the gene for diphtheria toxin?
Not encoded on the chromosome, but instead on a virus
Give some other examples of AB toxins.
- Tetanus
- Botulism
- Cholera toxins
What are super antigens? Describe them.
-Activate T cells to elicit an extreme immune response
-Bind to MHC molecules and TCRs outside the antigen binding sites
-Bridge the gap and mimics proper antigen presentation
-Huge number of T cells can be activated
-T cells produce cytokines
-Extreme immune response
-Extreme fever, systemic inflammation, shock, death
Ex. Staph aureus’s toxic shock syndrome.
What does systemic inflammation cause?
Vasodilation - which can induce shock
Salmonellosis (a food borne illness) is another example of how endotoxins are produced. Describe how it harms the body.
- Salmonella colonizes the intestine and multiples to a huge number of bacteria
- As those bacteria die, they release endotoxin
- Can cause fever, diarrhea, or generalized inflammation
Gram negative sepsis is another example of how endotoxins are produced. Describe how it harms the body.
- Gram negative bacteria multiply in the blood
- Killed by immune system, which releases an endotoxin
- Causes massive inflammation and leads to septic shock and death
What are more harmful: endotoxins or exotoxins
Exotoxins
