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25 Cards in this Set

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Capsular polysacchardies(CPS)

1. Loose network of polysaccharides that covers the surface of encapsulated bacteria.


2. Repeating saccharide units linked by glycosidic bonds


3. serotypes differs by


a. Nature of saccharide repeats


b. nature of glycosidic repeats


c. introduction of branches btw chains


d. acetyl or phosphate group substitutions(phosphate is negative)


4. E. coli has 80 serotypes (K antigens) K1 causes meningitis in newborns

Major gram + pathogens that produce capsules


1.Streptococcus pneumoniae (90)


2. Group A streptococci


3. Group B streptococci (9)


4. Staphylococcus aureus (8)

Major gram - pathogens that produce capsules

1. Escherichia coli (80)


2. Klebsiella pneumoniae (77)


3. Haemophilus influenza (6)


4. Pseudomonas aeruginosa

Functions of bacterial capsules

1. Protection from desiccation(binds water molecule through sugars)


2. Adherence to surfaces or other bacteria


3. Resistance to complement-mediated killing


-it prevents interaction of bound C3b with phagocyte receptors because it masks surface structure


4. CPS trap antimicrobial peptides


5. Molecular mimicry: CPS containing host antigens.


-fucose, surface molecule on intestinal epithelial cell

Vi capsule from salmonella typhi

1. 135-kb DNA region SPI-7(salmonella pathogenicity island-7)


-absent from salmonella typhimurium


2. viaB locus(DNA region in SPI-7) encodes proteins for biosynthesis and export of Vi capsular antigen


3. Vi antigen is a linear polymer that is O-acetylated at C-3 position

Transport of the Vi capsule

1. Is driven by hydrolysis of ATP


2. UDP-GlcNAc as precursor, transformed into Vi-antigen

Iron acquisition systems

1. Iron is essential for bacterial growth except for Borrelia burgdorferi (lyme disease, uses manganese)


2. some essential proteins require iron as cofactor(cytochromes)


3. Fe3+ is highly insoluble. Mammals have hemoglobin, ferritin (cytoplasmic proteins), transferrin(serum), lactoferrin(mucosal secretion to bind them.


4. free iron concentration (10^-18) too low to sustain bacterial growth.


5. Bacteria acquire Fe3+ via synthesis and secretion of low-molecular weight Fe3+-chelating compound siderophore in both gram +/-.

Siderophores from different bacteria

Structure may vary but always have phenolic groups that bind iron.

Enterobactin with and without Fe3+

Enterobactin is siderophore of E. coli


1. 6 oxygens from 3 diphenolic groups bind to iron


2. Estimated Kd of 10^-52 M, very high affinity for iron

Iron uptake in gram negative bacteria

1. Siderophore secreted to the extracellular environment


2. siderophore bound to iron passes through OM TonB dependent receptor(conformational change w/ energy provided by ExbB/D proton gradient) to enter perisplasm


3. Perisplamic protein binds siderophore-iron and is translocated through IM via ABC transporter (ATP required)

Iron uptake in gram positive bacteria

1. Siderophore mediated


2. Xeno-siderophore transport


-highjack siderophores loaded w/ iron produced by other bacteria


3. heme mediated


-extract heme from hemoglobin


-heme is then degraded once entering cytoplasm

Lipocalin 2

1. Neutrophils and epithelial cells release innate immune protein lipocalin-2(Lcn2)


2. Lipocalin-2 binds iron-laden entrobactin-type siderophores, making them inaccessible for bacteria

Salmochelin

1. produced by enteric pathogens: salmonella, E. coli, Klebsiella pneumoniae.


2. glycosylated derivative of enterobactin that is not targeted by lipocalin-2. Growth advantage to those pathogens


3. Salmochelin is produced by iroBCDEiroN gene cluster in S. typhimurium.

S. typhimurium vs E. coli nissle 1917


for iron

1. S. typhymurium colonization results in colitis


2. Inoculation of E. coli Nissle 1917 results in significant reduction of S. typhymurium colonization


3. E coli is able to acquire iron through systems that are not targeted by lipocalin 2.


4. S. typhimurium only has 2 iron uptake system

Lipopolysaccharide

1. endotoxin refers to LPS, main component of gram negative OM.


2. composed of:


- O side chains -oligosaccharides (species or serotypes antigens)


- Core polysacchardie (genus specifc antigens)


- Lipid A (toxic moiety)



3. Endotoxins are released after cell lysis, exotoxing are secreted from live bacteria



Lipid A

1. Contains hydrophobic region of LPS


2. in E. coli, consists of 2 phosphorylated NAG (N-acetylglucosamine) with 6 fatty acids attached (C12/14/16)


3. FA are usually saturated, some attached directly to NAG, others are esterified to 3-OH grp of FA.


4. Lipid A is the toxic component of LPS, is recognized by TLR-4.


5. When bacteria lyses, lipid A causes inflammation, septic shock in a few cases

Structural diversity of lipid A

1. Composed of a combination of C12 laureate, C14 myristate and C16 palmitate


2. Hexa-acylated lipid A is a potent TLR-4 activator(causes septic shock)


3. Tetra-acylated lipid A poorly activates TLR-4

Recognition of LPS by TLR4

1. LPS forms a complex with LBP (LPS binding protein) which binds to cell surface CD14.


2. This then forms complex with TLR4 and MD2


3. Resulting in signaling cascade triggered


4. activation of NFkB and MAP-kinase pathways in turn, inflammation


5. inflammation results in either infection clearance or septic shock

Core polysaccharide

1. attached to the 6 position of one NAG, consisting of a short chain of sugars


2. in E. coli: KDO-Hep-Hep-Glu-Glu-Gal


3. 2 unusual sugars usually present: 2-keto-3-deoxyoctonoic acid(KDO) and heptose. KDO is unique to LPS and invariably present in LPS.


4. core polysaccharide is common to all members of a bacterial genus with minor variation. It is structurally different between genera.

O-polysaccharide

1. also known as O-antigen, attached to core polysaccharide, is the antigenic part of LPS


2. consists of repeating oligosaccharide units made up of 3-5 sugars. length from 0 to 50 repeat units


3. great variation occurs in the nature of the sugars between bacterial strains.


4. In E. coli, there are 167 different O serotypes.

Lipooligosaccharide (LOS)

N. gonorrhoaea, N. meningitis and Chlamydia trachomatis

Export of LPS to OM

1. MsbA(ABC transporter) flips nascent


core-lipid A to outer leaflet of IM


2. O antigen is ligated to core-lipid A by O-antigen ligase WaaL


3. LptBFG (ABC T) with LptC and periplasmic LptA translocate LPS to inner leaflet of OM


4. LptDE (OM) flips LPS to outer leaflet.

Covalent modification of LipidA

responsible for resistance to antimicrobial peptides


1. decrease electrostatic interactions between lipid A and AMPs


2. decrease the permeability of LPS to AMP

Modifications of Lipid A in S. enterica

1. incorporation of 4-aminoarabose by prmE and/or phosphoethanolamine by pmrC


2. addition of palmitate (C16) by pagP


3. deacylation at the 3 position of lipid A by pagL


4. Hydroxylation of fatty acids by lpxO

Salmonella regulation of AMP resistance

1. S. enterica senses AMPs through PhoQ Sensor kinase that binds to AMPs.


2. PhoQ binding to AMP results in activation of PhoP(TF for LPS modying enzymes), LPS modifications and AMP-resistance