1. prevent killing from phagocyte --> decouple Fc from Fab 2. coat bacteria with non-functional Fab fragments to shield it from immune system

CHALK TALKS Flashcards by Zara Jalil

What is BCG?

Live attenuated vaccine of M. bovis

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How does BCG change the immune system>

induces epigenetic, transcripitonal, and functional reprogramming for TRAINED IMMUNITY

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Effects of BCG vaccine on transgenic mice expressing human ACE2 with COVID infection

no change in mortality or viral load

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how did they measure viral load of COVID (2)

TCID50 and plaque assay

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effect of BCG vaccine on syrian golden hamster naturally expressing ACE2 with COVID infectio

no change in mortality or viral load but decrease body weight

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roborovski hamster model

develops severe COVID phenotype

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effect of BCG vaccine on roborovski hamster which COVID infection

no change in mortality or viral load but decrease body weight

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how does COVID affect BCG trained immunity?

COVID causes vascular damage –> then virus disseminates to BM and prevents trained immunity by BCG

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Is A. baumannii gram positive or negative?

gram negative

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3 reasons why CRAB is antibiotic resistant

complex OM
LPS shields it from immune system
efflux pumps

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first candidate antibiotic for CRAB

protects mice from CRAB but causes mortality and moribund

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4 benefits of second generation drug: ZAB

decreased lipid plasma precipitation/increased lipophilicity
decreased cholesterol, TAG, HDL
increased solibility and stability
decreased non-specific binding

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what is the target of ZAB?

inhibits LPS transporter –> blocks LPS extraction from membrane and kills CRAB

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why is there likely resistance to ZAB?

Only has 1 target

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ZAB effect in vitro and in vivo

in vitro: decreased MIC
in vivo: dose-dependent decrease in bacterial burden

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is S. pneumoniae gram pos or neg?

gram pos

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current treatment for S. pneumoniae?

1 benefit, 2 downsides

POLYSACCHARIDE-based vaccines

benefit: effective for invasive S. pneumoniae

downside: only targets some serotypes and less effective in mucosal infection

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what is IgA1?

most frequently produced Ab

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2 forms of IgA1

Secreted (dimer)

Serum (monomer)

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where is IgA1p found?

on S. pneumoniae via G5 domain

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function of IgA1p?

requires Zn, cleaves proline-rich hinge on IgA1 heavy chain

N-terminal beta-helix shifts to accomodate IgA1 (open conformation)

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drug against IgA1p?

mAb that holds IgA1p in closed conformation

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2 purposes of IgA1p?

prevent killing from phagocyte –> decouple Fc from Fab
coat bacteria with non-functional Fab fragments to shield it from immune system

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how and where is DNA-delivered mAb delivered?

delivered via plasma

expressed and secreted by skeletal muscle cells so it can directly enter systemic circulation

2 reasons why it's important that DMAb directly enters systemic circulation

1. prevent virulence 2. promote bacterial clearance

2 PA virulence factors that DMAb are engineered against

1. Psi exopolysaccharide 2. T3SS

describe specificity of DMAb

less DMAb in serum = less Ag recognition and binding

can DMAb be expressed long term?

yes, 100-120d

5 reasons why DMAb can be protective against PA

1. dose-dependent protection against PA 2. reduced lung bacterial burden 3. reduced cytokine and chemokine levels 4. reduced inflammation 5. increased survival when combine with other antibiotics

5 benefits of DMAbs

1. cheap 2. good safety 3. better administration 4. less frequent administration 5. more temp stable

is C diff gram pos or neg?

gram pos

why is it good to study microbiota in post-menopausal women? (3)

1. sex hormones feed on microbiota 2. sex hormones may lower gut microbiome diversity 3. more similar to male microbiome

6 effects of VLCD diet on microbiome

1. reduced colonization 2. reduced bacteria that metabolize plant sugars 3. increased bacteria that metabolize host glycans 4. increased enzymes that metabolize sugars and produce SCFA 5. reduced BCAA 6. reduced SCFA

what happens in a post-diet microbiome?

causes weight loss

why is there weight loss in post-diet microbiome?

reduced energy absorption

why is there reduced energy absorption in post-diet microbiome?

increased caloric density in stool, reduced adiposity

role of C diff on weight loss and metabolic changes

C diff INDUCES weight loss and metabolic changes without causing colitis - weight loss depends on toxins

how does caloric restriction affect C diff? why?

caloric restriction causes increased C diff growth - less emptying of primary bile acids - less gut bacteria, less secondary bile acids

C diff life cycle and where primary/secondary bile acids play a role

spore -- germ. --> vegetative -- growth --> toxin production primary bile acids induce germination secondary bile acids block growth

3 things that happen in EUBIOSIS

1. increased SCFA 2. diverse microbiota 3. anaerobic environment

4 things that happen in DYSBIOSIS

1. decreased SCFA 2. increased bacteria colonization 3. aerobic environment 4. increased inflammation

amounts of primary and secondary bile acids in antibiotic treated microbiome

more primary, less secondary

example of primary bile acid induced by antibiotic and how this affects germination

Taurochol --> increased germination

example of secondary bile acid when there's no antibiotic and how this affects germination

Deoxycholate --> decreased germination

what happens to amount of sugar alcohols in antibiotic treated microbiome?

increased sugar alcohols

3 consequences of increaed sugar alcohols in antibiotic treated microbiome

1. increased growth lag 2. increased growth rate 3. increased final cell density

what happens to sugar glycolytic pathway in antibiotic treated microbiome?

it is decreased

which 2 phyla affect metabolites in gut? how do they affect gut? (2)

Firmicutes and Bacteroidetes 1. metabolize bile acids 2. ferment carbohydrates into SCFA

describe Firmicutes

forms spores and inibits C diff spore germination by decreasing primary bile acids and increasing secondary bile acids

what is SER-109?

purified Firmicutes spores

3 effects of SER-109

1. prevens CDI recurrence 2. engraftment during wk 1-8, more sustained clinical response 3. increased secondary bile acids

describe the 2 pronged treatment

vancomycin/fidaxomin (kill toxin-producing bacteria) + SER-109 (inhibit germination)

is S. aureus gram pos or negative?

gram positive

bacteria that can be used as probiotic?

B. subtilis

describe B. subtilis

gram positive --> forms spores that germinate in intestine and compete with harmful bacteria

what is Fengycin?

produced by B. subtilis and inhibits S. aureus quorum sensing to block colonization

describe B. subtilis probiotics in vitro

reduced S. aureus

describe B. subtilis probiotics in vivo

fecal colonization but alpha and beta diversity no difference