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51 Cards in this Set

  • Front
  • Back
What is microflora?
Bacteria that are harmless and beneficial to the host.
Are there more eukaryotic or bacterial cells in our bodies?
Bacteria (10^14 bact cells)
Euk: 10^13 cells
Where do most of the bacteria reside?
GI tract
Also in mouth, skin, esophagus, colon, stomach, vagina
How many types of bacterial phyla are there?
50 phyla, but most of the human microflora are dominated by 2 phyla
look at figure page 2 to see distribution of bateria in dif organs
look at figure page 2 to see distribution of bateria in dif organs
Where do these bacteria come from?
Fetus sterile
From birth, humans are colonized by bacteria, archea, viruses and fungi
-Transmission depends on close contact with the mother (similar intestinal microbiota of infants and vanginal microbiota of mothers)
->Babies delivered by c-section have dif colonization patterns compared with vaginally-delivered infants
What is the succession of species that colonize babies?
1st: Facultative anaerobes (Streptococci)
Next: Obligate anaerobes
Where are the bacteria in the GIT?
Stomach: 10 (lactobacillus. vellionella, helicobact)
Duodenum:10^3
Jejunum:10^5
Illeum: 10^7
(all 3: bacilli, streptococcaceae, actinobacteria, actinomycinaeae, corynebacteriaceae)
Colon: 10^12 cells/gram (lachnospiraceae, bacteroidates)
Wy are there so few bacteria in the stomach?
Very low pH
focus on heliobacter
Where are the bacteria in the epithelium?
Epithelial surface, mucus layer, intestinal lumen
Where do bacteria bind in the epithelium?
Mucous layer
mucin can bind polysac and IgA

->Most bacteria bind the lumen
Why did scientist analyze the 16S rRNA sequences from fecal samples?
All the bacterial species have similar enough 16S sequences to be recognizable
Different enough to separate each species
How many species are there in the gut?
400-500
Majority of the species are uncultivalble
What is the human metagenome?
Human genome plus "our" microbial genomes (the microbiome)
-The gut microbiota can be seen as an additional metabolic organ
What is the point of metagenomics?
Try to ID genes and reconstitute genomes
Increase # of predicted species in the gut (~1200)
(Haven't reconstituted an entire bact genome yet)
What kind of bacteria are the vast majority of the gut microbiota?
Strict Anaerobes
What 2 bacterial phyla dominate the gut microbiota?
Bacteroidetes
Firmicutes
(make up 98% of all bacteria)
What are the phyla present in minor proportions?
Actinobacteria
Fusobacteria
Proteobacteria
Verrucomicrobia
Cyanobacteria
Describe Bacteroidetes.
50% of gut bacteria
G-
Non-flagellated
Non-fimbriated
What are the species of bacteroidetes?
Bacteroides vulgatus (31%)
Bacteroides thetaiotaomicron (12%)
Bacteroides fragilis (5%)
Where do bacteroides bind?
mostly to mucous layer, as well as some food particles and mucous pieces floating around
Describe Fimicutes.
mostly G+
Facultative anaerobes
Include the species:
-Bacillus
-Enterococcus
-Lactobacillus
-Lactococcus
-Clostridium
-Streptococcus
What are archaea?
Look like bacteria
Are unicellular organisms
Have no nucleus
Have some features that are similar to eukaryotes (ex: translational machinery)

->split off from bacteria, but before eukaryotes
-> are present in the gut
Germ-free mice were colonized with Bacteroides thetaiotaomicron with or w/o
Methanobrevibacter smithii (the archeon) (produces methane).
What were the results?
Presence of the archaea enhanced the ability of the bacteria to degrade fructans (polysac)
Archaea drive carbohydrate utilization by removing products of fermentation (H2, CO2 and short-chain organic acids are converted to methane)
-Co-colonization is associated with a significant increase in host adiposity
What is a prophage?
DNA sequence inserted in bacterial genome
Can be excised andinfect another bacteria and bring that DNA with it to a new species
What is a bacteriophage?
Virus that only infects bacteria (doesn't integrate itself into the bacterial DNA)
Prophage:viral genome integrate into the bacterial chromosome
What is the result of this transfer of genes from one bacteria to another?
Affect bacterial metoabolism
Can prevent gut metabolism
What are the main fcts of the gut microflora?
-Colonization resitance
-Modulation of the host physiological fcts
-Digestion of plant polysaccharides (dietary fiber) and host-deribed mucopolysac
-Dev'p of theintestinal immune system
What happens if you restrict microbial growth?
Pathogens that remain have more food and more room to grow
What is colonization resistance?
Normal microflora are a barrier to colonization by transient pathogens by spatial inhibiton
->Competition for receptor sites of adhesion (btw path and normal flora)
-Competition for essential endogenous nutrients and co-factors
-Creation of microenvironments that prevent the growth of exogenous species
-Production of inhibitory factors (bacteriocin, H2O2, acids, etc)
What happens when a large spectrum of antibiotics are used?
Resident microflora are affected
Disrupt the colonization resistance
Favor colonization by pathogens or opportunistic pathogens (C. difficile)
Why do pathogens cause an immune response, while normal flora doesn't?
Paths trigger inflammation because they have PAMPs (flagellin, LPS etc) which are recognized by TLRs/NOD-like receptors
What happens when mice are infected with WT and avirulent S. typhimurium? (mutant lacks both type-III secretion systems)
WT: Big dif in microflora. Inc inS. typh. and no S. typhi (look at graph pg. 9)
Mutant: Nomuch change in microflora
What happened to germ-free mice colonized with Bacteroides thetaiotaomicron?
Intestinal transcriptional response
-> the presence of the bacteria modulated the expression of host genes involved in important intestinal fcts
--> epithelial fucosylated glycans, nutrient absorption, mucosal barrier fortification and postnatal intestinal dev'p
Describe digestion of plant polysac
Normal microflow let host get E from plant carbs that they would otherwise not use (pectin, cellulose, starches)
-Bacterial metab of plant carbs in the gut produces short-FA (acetate, propionate)
->this accounts for >10% of our daily absorbed calories
What kind of bact is B. thetaiotaomicron?
Glycophile
What is a glycophile?
Loves carbs/sugars
What does B. thetaiotaomicron have that helps it diegest sugars?
163 OMPs that bind carbs
172 glycosylhydrolases

(simple sugars absorbed through intestinal villi used by GIT microflora)
What happens if there is no polysac available to the bact?
They use mucopolysac found in the muscoue layer (but prefer regular carbs)
How does B. thetaiotaomicron get its carbs?
1) Doens't have fimbriae .: can be washed out of gut
2) Uses OM glycan binding ptns to interact with food particles, shed host epithelial cells and/or mucous fragments
3) Methanogens (archaea) drive carb utilization by removing products of fermentation
4) Uses host mucous by expressing dif polysac binding ptns and glycoside hydrolases if dietary polysac not available
Does B. thetaiotaomicron ever stick to the epithelial layer?
No (this would cause inflammation)
-> only ever touches epithelial cells that are floating around

->microflora don't have the tools required to penetrate mucous layer and get into epithelium
Howis starch 1st digested?
In the mouth by amylase
Becomes stable in the intestine
How many Sus genes are there on the us operon?
8
How does B. thetaiotaomicron break down starch?
SusC and SusD: OM ptns that bind starch
What does Sus G do?
Limited hydrolysis of starch into small peptides (at the OM)
What does SusA do?
Extensive hydrolysis of starch in periplasm
What happens after SusA digestion?
Uptake of oligosac across the cytoplasmic mb
What are the Beneficial effects of Bacteroides fragilis
polysaccharides on the immune system?
-B. fragilis makes 8 capsular polysac (CPS) : PSA - PSH
-At least 1 CPS needed for competitive colonization of the colon (protection vs innate immune defense)
What is PSA?
Immunomodulatory molec
How is PSA beneficial to the immune system?
Activates CD4+ T cells and elicits appropriate cytokine production in the GALt
->prevents the dev'pof colitis in an experimental model of inflammatory bowel disease (IBD)
What effect does Butyrate have on host?
Cell prolif
Anti-cancer properties
Transcription of genes coding for AMPs
(link btw fiber and decreasing the chance of colon cancer)