Bacterial Structure Flashcards
What does peptidoglycan consist of?
A repeating disaccharide of NAG and NAM
What is NAG?
A monosaccharide derivative of glucose
An amide between glucosamine and acetic acid
What is NAM?
A monosaccharide derivative of NAM (ether of lactic acid and NAM)
What are NAG and NAM cross-linked with?
Oligopeptides at the lactic acid residue of NAM
How do cross-linking peptides differ between Gram-negative and Gram-positive bacteria?
MAIN DIFFERENCE: Gram-positive links tetrapeptides with a pentaglycine crosslink and Gram-negative tetrapeptides link directly to other tetrapeptides
Gram-positive = 9-13 aa long
Gram-negative = 8 aa long
What is unique about D isomers and why do bacteria use them in their PG?
They are uncommon in nature and are used by bacteria to avoid protease digestion
Why does gonorrhea have some resistance to antibiotics?
Because they have highly cross-linked PG layers
What is the LPS a major component of and what does it do?
The outer membrane of Gram-negative bacteria
It is important for the structural integrity of the bacteria and protects the membrane from chemical attack
What does the LPS do to the charge of the cell membrane and why does it do that?
It increases the negative charge
Helps stabilize the overall membrane structure
What does LPS associate with and why?
Divalent cations (Mg++) to neutralize charge repulsion
What are the 3 molecular domains of LPS?
Lipid A
The core
The O-antigen
What is the structure of Lipid A and what does it allow?
Phosphorylated glucosamine disaccharide with associated fatty acids
The fatty acids allow bilayer formation and it is antigenic
What is the core made up of and what does it attach to?
The core is made up of mostly sugars (can contain amino acids) and it attaches directly to lipid A
Diverse
What is the O-antigen attached to and what does it determine?
It is attached to the core oligosaccharide and due to it being highly diverse, it often determines strain type
What are the implications of O-antigen being presented on the cell surface?
It is antigenic and therefore the bacteria are always changing it
What are long O-antigens associated with?
Virulence
What does smooth O-antigens make?
A gel and it appears smooth
What are rough O-antigens associated with?
Non-pathogens
What part of lipid A anchors the LPS into the bacterial membrane? Where is the rest of the LPS?
The hydrophobic fatty acid chains anchor LPS into the cell membrane
The rest of the LPS projects from the cell surface
What is the lipid A domain responsible for?
The toxicity of Gram-negative bacteria
When bacterial cells are lysed, what does the release of lipid A into circulation cause?
Fever
Diarrhea
Endotoxic shock (sepsis)
What types of bacterial PAMPs can PRRs detect?
PG
Lipid A
Teichoic acid (links layers of Gram-positive PG)
Capsules
What do TLRs do and where are they expressed?
They recognize PAMPs
They are expressed in all cells of the innate immune system and can be found on the cell surface or inside endosomes
Where are endosomes located?
In between the plasma membrane and Golgi
What does TLR6 recognize?
PG in Gram-positive
Lipoteichoic acid in Gram-positive
Lipoproteins of Gram-negative
What does TLR4 recognize?
LPS in Gram-negative + LPS with co-receptor MD2
What does TLR3 recognize and where is it found?
Detects intracellular and phagocytized pathogens
Found in endosomes
What are NODs and what do they detect?
Nucleotide-binding domain, Leucine-rich repeat-containing receptors
They detect intracellular PAMPs
Why is there often an overlap between TLRs and NODs?
They can detect the same pathogen
Where is H. pylori found, what is unique about it, and what does it cause?
It infects the gut lining
It is acid tolerant
It can cause acute gastritis and chronic inflammation
How does H. pylori survive in the gut?
It secretes a base to neutralize the acid and liquifies mucous
Its flagellar bundle and spirochaete shape allows it to penetrate the mucous layer
Which NODs recognize H. pylori?
NOD-1 and NOD-2
What does NOD-2 recognize?
PG from both Gram-positive and Gram-negative
What does NOD-1 recognize?
A modified dipeptide commonly found in Gram-negative (mDAP)
What is the cause of listeriosis and who is most susceptible?
Eating contaminated food
Pregnant women, infants, old people, and the immunocompromised
What foods should pregnant women avoid to not get listeria?
Soft cheese and raw milk
What temperature can Listeria survive at and what type of pathogen is it?
0°C-37°C
Opportunistic
How does listeria attach to a host and what can it survive?
Attaches to the host via D-galactose (sugar on surface)
Can survive phagocytes and manipulate host cytoskeleton
What is unique about the peptidoglycan of listeria?
50% of NAG is replaced with glucosamine by the PgdA enzyme which is a virulence factor so that the host cannot recognize it
What does deacetylation of listeria PG allow the evasion of?
NOD-1
What are 3 ways that listeria evades NLRs?
Deacetylation of NAG by PgdA
Glycosylation of teichoic acid = enhances virulence
Lysine is added to cell walls to increase the positive charge
What is the purpose of adapting to enhance positive charges?
Normally bacteria are negatively charged
By enhancing positive charges, it allows the avoidance of CAMPs
What is Kdo2-lipid A?
The most common sugar in core oligosaccharides
What are the enzymes to modify Kdo?
periplasmic
What are modifications of Kdo2-lipid A essential to avoid?
AMP
TLR4
How does Y. pestis modify Kdo2-lipid A?
Glycosylation to PO4-
How does H. Pylori modify Kdo2-lipid A?
Only has 4 acyl chains
Masking of a negative charge on PO4-
How does P. aeruginosa modify Kdo2-lipid A?
Glycosylation of PO4- to shield negative charges from AMP
How does V. cholerae modify Kdo2-lipid A?
Addition of PO4
Addition of acyl chains
What are the 3 lipid A evasion strategies that H. pylori uses?
- dephosphorylation = lose PO4- to remove negative charge which adds resistant to CAMPs
- Removal of the negative charge by adding an amine
- Fewer HC tails as hexacylated lipid A is very antigenic
What does the temperature change from fleas to humans cause in Y. pestis?
Causes a change in gene expression which turns on virulent genes
What does Y. pestis look like in fleas?
Has a hexacylated lipid A but is not antigenic to the flea
What does Y. pestis do in humans?
An enzyme is activated with the temperature shift that cleaves 2 acyl chains which makes it TLR4 evasive
At which temperatures is Y. pestis virulent and non-virulent?
Virulent = 37°C
Non-virulent = 25°C
What evasion strategies on lipid A does V. cholera use?
Addition of a diglycine to lipid A which decreases AMP sensitivity
What type of illness is cholera?
Water-borne illness that exists in copepod reserviors
What are AMPs and what can they kill?
Nonspecific components of the immune response, like to punch holes
Can kill Gram-negative and Gram-positive bacteria `
What are the subgroups of AMPs?
Alpha-helices
Beta-sheets
Mixed alpha/beta
Cyclic
Extended
Where might alpha-helix AMPs be found?
In the lysosome of macrophages
What is Kalata B2?
Found in plants and has been shown to have insecticidal, anti-tumor, and antimicrobial functions
CAMPs that detect negative surface charges
How do AMPs kill bacteria?
By making pores
What are defensins?
Short peptides with an positive charge and a lot of hydrophobic residues that allows it to adopt amphipathic structures in membrane-mimicking enviornments
Where is a high concentration of defensins found and what might they aid in?
Breast milk
Colonization of the gut
How do Gram-positive bacteria resist defensins?
Modification to cell wall teichoic acid to decrease negative charge
Add positively charged membrane proteins to offset negative charge
How do Gram-negative bacteria resist defensins?
Modification to LPS = more acyl chains = harder for AMP to penetrate
Secrete negatively charged proteins which act as decoys for CAMPS
What is the last line of resistance to defensins?
Efflux pumps = pump out the AMPs
Proteases = destroy AMP
What is molecular mimicry?
Structural, functional, or immunological similarities shared between macromolecules found on pathogens and in host tissues
What can molecular mimicry induce?
Autoimmune responses which attack and destroy body tissues or organs
What is Guillain-Barre’s syndrome?
An infection with Campylobacter that causes autoimmune disease
temporary
How does C. jejuni showcase molecular mimicry?
The LPS of C. jejuni has evolved molecular similarity to GH1 gangliosides in human neurons
