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109 Cards in this Set

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What is the shift that we are seeing now in preventing/treating bacterial infections?
Past: antimicrobials focused on structural characteristics
Now: genomics and enzyme targets
What unique ability do MICROBES have that eukaryotes have less?
The ability to ADAPT to their environment
How do microbes adapt?
Via mutations in their metabolic pathways
2 types of agents that we have for combat against microbes:
-Vaccines
-Antimicrobial agents
What are 4 accessory structures on microbes?
-Flagella
-Fimbriae
-Capsules
-Secretion mechanisms
What targets the cell wall?
What targets accessory structures?
Cell wall: antibiotics

Accessory: vaccines
What really makes microbes unique?
Their replication process
How do bacteria replicate?
Thru binary fission
What do bacteria achieve by being able to divide rapidly?
Rapid selection and adaptation to environmental changes.
What bacteria take a LONG time to replicate?
Mycobacteria - like weeks.
What is the implication of bacteria being able to replicate phenomenally rapidly, and mutate to adapt to their environment?
It is very difficult for hosts to control the organism.
What is the fuel that bacteria use for growth?
Carbohydrates
What bacteria utilize amino acids?
Clostridia
What bacteria utilize fatty acids?
Leptospira
What makes the bacteria that utilize AA's and FA's special?
They have a selective advantage bc they don't have to compete with other bacteria for carbs.
What is the limit of detection for the human eye?
~30 micra
What size are most bacteria?
0.4 - 2 micra
How big are viruses in comparison to microbes?
Smaller than the smallest bug
What is the biggest virus? Why?
The pox virus - because it carries its own synthetic machinery in its genome.
What are the smallest microbes that are a little smaller than the pox virus?
Rickettsiae and Mycoplasma
What defines the shape of bacteria under the microscope?
The cell wall peptidoglycan
What microbes form chains of cocci?
Streptococci
What microbes form tetrads of cocci?
Micrococci
What microbes form grapelike clusters of cocci?
Staphs
What are spiral shaped bacilli?
Spirochetes
What are comma-shaped bacilli?
Vibrio
What is the cytoplasm of prokaryotes like compared to eukaryotes?
Simple
What are the cytoplasmic constituents of prokaryotes?
-Ribosomes
-Nuclear area (unenveloped)
What makes prokaryotic cells distinct from eukaryotic?
Their cell wall
What does the nuclear area of bacteria contain?
A single molecular chromosome covalently closed and circular.
What is the main reason for why the eukaryotic cell is set up in very compartmentalized, organized ways?
To maintain HOMEOSTASIS
Why do prokaryotes lack such organization?
They don't WANT homeostasis - they want to be able to adapt very rapidly and mutate.
What is the site of cell respiration in
-Prokaryotes
-Eukaryotes
Proks: inner cell membrane
Euks: mitochondria
What is the innermost membrane in microbes?
The cell membrane (phospholipid bilayer)
What is just external to the cell membrane?
The periplasmic space
What is external to the periplasmic space?
The cell wall
What is the cell wall made up of in gram pos organisms?
-a THICK layer of peptidoglycan
-Teichoic acid
What is the cell wall made up of in gram neg organisms?
-a thin outer membrane
-peptidoglycan
-LIPOPOLYSACCHARIDE
What lies external to the cell wall?
Accessory structures like the capsule
In which membrane are flagella anchored?
The inner cell membrane
What is the purpose of the Teichoic acid in the peptidoglycan of the thick outer membrane in Gram pos microbes?
It stabilizes the peptidoglycan
What function does the peptidoglycan cell wall serve?
As a permeability barrier to prevent lots of stuff from entering.
What structure on gram negatives serves as the permeability barrier?
The OUTER membrane
What is the outer membrane made up of?
More phospholipid bilayer, with LPS within it which sends polysaccharide chains out on the surface of the microbe.
What lies between the LPS/outer membrane and the inner membrane?
The periplasmic space containing a thin peptidoglycan layer which is crosslinked to lipoproteins in the outer membrane.
What is the basic subunit of peptidoglycan made up of?
A disaccharide linked to a D/L pentapeptide
What is the disaccharide?
N-acetyl glucosamine in a B1,4 linkage with N-acetyl muramic acid.
What is the pentapeptide made up of?
-L-ala
-D-glu
-L-Lys
-D-ala
-D-ala
What is the feature of the 3rd amino acid always in the pentapeptide?
It is DIBASIC so it can be used for cross-linking - an NH2 (lysine)
What is the immature structure of the peptidoglycan basic subunit?
5 amino acids
What is the mature structure of the peptidoglycan basic subunit?
Only 4 amino acids - the 5th (alanine) is cleaved to allow for cross-linking.
What is different between gram neg and gram pos structures of peptidoglycan?
Gram pos: highly crosslinked
Which saccharide in the disaccharide is the pentapeptide chain linked to?
Muramic acid
So how are pentapeptide chains crosslinked in gram pos peptidoglycan?
Between the 3rd (C) amino acid on one chain, and the 4th (d) amino acid on adjacent pentapeptides.
Why is it good that Peptidoglycan is unique to prokaryotes?
It is the site of action of many antibiotics.
What is different about the peptidoglycan structure in gram negs compared to gram pos?
It has very little crosslinking.
What is the purpose of gram pos peptidoglycan being more crosslinked than gram neg?
Gram pos = very strong
Gram neg = fragile
What defines the structure of bacterial cells?
Peptidoglycan
What natural antimicrobial agent cleaves peptidoglycan?
Lysozyme
What antibiotic inhibits cell wall synthesis?
Penicillin
To what 2 structures is Teichoic acid in Gram pos cells linked?
-Cell wall peptidoglycan
-Cytoplasmic membrane
What is the peptidoglycan in gram neg cells crosslinked to?
Lipoproteins in the outer membrane
What is the main significance of the differences in PG thickness and crosslinking in gram neg versus pos?
-PG serves as an effective permeability barrier in GP bugs
-Not an effective barrier in GN bugs
What is the permeability barrier in gram neg bugs?
the Outer Membrane
What is the outer membrane in gram neg bugs permeable to?
Molecules less than 600 Daltons in size
What is the main component of the gram neg outer membrane that sets it apart from gram pos bugs?
LPS - lipopolysaccharide
What is the function of LPS?
-Cell growth
-Stimulates innate immunity
What does LPS consist of?
-O-antigen repeating subunits
-Core polysaccharide
-Lipid-A
What is another name for LPS?
Endotoxin
What does Lipid A cause?
Fever - it is toxic
What is O Antigen?
Side chain polysaccharide - useful in diagnostics because its different between different gram neg bugs; Antibody binds it
So again; the 3 components of LPS are:
-Lipid A
-Core polysaccharide
-O antigens
And what part of endotoxin causes fever?
Lipid A
What are O antigens?
Side chain polysaccharides that are individual and unique for different enterobacteriaceae.
How are O antigens used for diagnostics?
By using specific antibodies directed agaist O antigens they allow differentiation of bugs.
What are the 2 main antigenic structures in the cell envelopes of bacteria?
-LPS
-LPA
What type of structure do the LPS and LPA molecules have?
Amphiphilic
What do LPS and LPA give to bacteria?
Membrane stability
What do LPS and LPA stimulate?
Innate immunity
What is Innate Immunity?
What is it performed by?
-Immediate response to infection
-Macrophages and Neutrophils
What are the molecules on bacteria that receptors on Macrophages and PMNs bind to?
PAMPs
What are 5 PAMPs? On what organism is each molecule?
-LPS on gram neg bugs
-Lipoteichoic acid on gram pos
-Mannon on yeast
-Lipoarabinomannon on mycobactm
-Lipoprotein on eubacteria
What is special about PAMPS?
They DON'T mutate; they have to remain the same for bacteria to survive.
What is the general name for the receptors to PAMPs?
TLRs
Where were toll receptors first studied?
In drosophila flies
What is different in human Toll like receptors compared to the Toll innate response molecules in Drosophila flies?
The EFFECTORS:
Flies: make antibacterial peptides
Humans: make cytokines
How did we figure out that there are SPECIFIC TLRs to different PAMPs?
By knocking out various TLRs in mice.
What happens when TLR4 is knocked out?
Failure to respond to LPS
What is key to remember about TLRs?
They provide the link between Innate immunity and Adaptive immunity by the stimulation of Cytokine production!
What are 2 structures involved in bacterial Adherence? Which is bigger?
Fimbriae (small)
Pili (large)
What are Fimbrae and Pili made up of?
Single protein polymers
Why are adherence proteins like Fimbriae and Pili important?
Because they allow for bacteria to COLONIZE and start up the pathogenic process.
What other pathogenic process are pili involved in?
Intrabacterial adherence for exchange of resistance/virulence factors.
What bacterial structure functions as a virulence factor by preventing phagocytosis?
The Capsule
What are capsules composed of?
Protein or Polysaccharide
What stain is used for capsules?
Negative staining
What is an important accessory appendage that achieves bacterial motility?
Flagella
What are flagella made of?
Where are they anchored?
Protein polymers; anchored in the cell inner membrane.
What bacteria have one polar flagellum?
Pseudomonads
What bacteria have flagella distributed over their entire cell surface? What is this arrangement called?
Enterobacteriaceae - peritrichous.
What happens when flagella genes are mutated leaving the bacteria nonmotile?
That makes the bacterium avirulent.
What bacterium is SO motile that it just swims all over the agar?
Proteus - swarms
What is special about the flagella in spirochetes?
They are located within sheaths instead of on the exterior of the organism.
What are Flagella the evolutionary parents to?
Secretion systems!
What type of genetic mutation allowed for the evolution of flagella into secretion systems?
DUPLICATION
Does gene duplication alter the original flagella?
No; they are still able to do their thing.
What do Type II secretion systems do?
Secrete proteins across the inner membrane.
What do type III secretion systems do?
Deliver proteins into host cells
What do type IV secretion systems do?
Deliver DNA into host cells