EXAM Lecture 11 Flashcards
Gram negative bacteria cell wall
has a lipopolysaccharide lipoprotein phospholipid containing outer membrane which surrounds a thin PGN layer and NO teichoic acids
the outer membrane protects cell from phagocytosis by other cells and penicillin, lysozomes, etc
Porins are proteins that permist small molecules to pass through the outer membrane; specific channel proteins allow other molecules to move through the inner plasma membrane
“the two differentiators between - and +:”
1. two membranes
2. LPS in outermembrane
lipopolysaccharide (LPS) aka Endotoxin
- found in gram negative bacteria cell walls
made up of:
- Lipid A: anchors LPS to the membrane bilayer
- Core Oligosaccharide (aka core polysaccharide): variable chain of monosaccharides
- O-Antigen (aka O specific polysaccharide chain): “binds with receptor in host, most important, varies”
- sugars (O antigen) function as an antigen; stimulate host immune response and can be used to identify different bacteria strains based on composition of polysaccharide chain
-core polysaccharide; binds sugars to lipid A
endotoxin causes inflammation in the host (fever and shock) and the signalling pathway uses the receptors Toll Like Receptor 2 or 4 (TLR2 and TLR4)
- can have one or the other or both, both means more receptive
- “these are the host receptors that CPS binds to”
Endotexemia
LPS or endotoxin signalling stimulates production of many inflammatory cytokines: interleukin 1 and2, Tumor necrosis factor
mode of action: inflammation of epithelium/GI, blood vessel inflammation, etc
endotexemia symptoms: fever, changes in blood pressure, inflammation, can be fatal
- endotoxin is released from the cell walls of gram negative bacteria as they die or cell wall disintegrates
simplified TLR mediated signalling via TLR2 and TLR4 = inflammation
*watch lecture again slide20
LPS and endogenous ligands (saturated fatty acids) go through one of two pathways:
TLR2/MyD88 pathway:
- TLR2 or TLR4 signalling
- IRAK -> TRAF-6 -> TAK-1 -> NFkB activation
TLR4/TRAM pathway:
- TLR4 signalling only
- TRIF -> TRAF-6 OR RIP1 -> NFkB activation
NFkB activates:
- inflammatory cytokines: TNFa, IL-1, etc
- chemokines: MCP-1 (recruits other immune cells)
Microbiota definition
- collection of all microorganisms that reside in an established environment
- microbiome: all genetic material within a microbiota
- within each bacteria community, we need to think about diversity (WHO is present) and size/abundance (HOW much is present)
- bacteria that makes up a small % abundance can still have big impacts on host
- stability of the microbiota community structure is susceptible to various environmental stimuli (diet, antibiotics, etc)
- colon is the largest site for microbiota
The colonic microbiota: regional differences in bacteria localization (proximal vs distal colon)
review again slide 23
“regional difference: fecal samples reflect whats happening in distal colon but not proximal colon”
“structural difference: bacteria in the mucus can be different from non mucus”
luminal bacteria: reside in the lumen of the colon
mucus associated bacteria: reside in the outer mucus layer of the colon
- want these in mucus but not touching apical boarder
bacteria/microbiota impact many host functions
- bone mass density
- protect against epithelial injury
- resistance to pathogens
- breaking down food compounds
- modification of nervous system
- metabolism of therapeutics
- promotion of fat storage
relationship between microbiota and disease
exam question
microbes perform vital functions for the host related to:
- nutrition
- metabolism
- immunity
- susceptibility to disease
bacteria classified based on taxonomy and we can sequence the microbiota composition using 16S rRNA gene sequencing technology
- 16S is unique to bacteria vs 18S (eukaryotes)
- can identify diversity and abundance of bacteria in microbiota (= community structure) based on taxonomy
TAXONOMY
- domain
- kingdom
- phylum
- class
- order
- family
- genus
- species (MANY strains within each species)
Sequencing the human microbiota
Phylogenetic Core:
- 1/3 of total microbiota composition
- limited diversity
- preserved, abundant, limited taxa
- high abundance and common bacteria species to most healthy individuals (but very few taxa are common to everyone)
- a CORE microbiota that everyone needs
Unique individual:
- 2/3 of total microbiota composition
- high diversity
- low abundance, many taxa
- lower abundance and bacteria species that are NOT common to all individuals
- makes each persons microbiota unique AND may also impact disease susceptibility
Microbial diversity and abundance
- diversity and richness (abundance) is decreased in various disease states versus healthy ppl (but some diseases exhibit increased of both)
HEALTHY
- high diversity: many different types of bacteria
- high abundance: many total bacteria
DISEASED
- low diversity: fewer different types of bacteria
- low abundance: fewer total bacteria
Maintaining the equilibrium
Three main componenents we want:
- diversity
- abundance
- gene count (=low gene count = decreased functional capacity if microbiota)
high diversity of species:
- healthy ecosystem
- balance
- functional redundancy (high gene count)
- resistance to damage
low diversity of species:
- sick ecosystem
- imbalance
- function disability (low gene count)
- susceptibility to damage
Gut Microbiota continues to evolve throughout our entire life
Stages:
- prenatal
-postnatal
- puberty
- adult
- elderly
susceptibility to different diseases can vary with age
