11.19.17

CYSTIC FRIBROSIS

G511D mutation: missense mutation, Glycine replaced by Aspartate.

Only 5% of pts with CF have this mutation.

Defective channel opening or gating.

IVACAFTOR: new drug, acts directly in the CFTR channel, opens it up. First drug that afects the ethiology :)

Trade name: Kalydeco

This bedroom is soooo pretty, this colour palette is everything.

Tularemia as a biological weapon

It was viewed as an attractive agent because:

it is easy to aerosolize,

it is highly infective; 10-50 bacteria are required to infect,

it is nonpersistent and easy to decontaminate (unlike anthrax),

it is highly incapacitating to infected persons,

it has comparatively low lethality, which is useful where enemy soldiers are in proximity to noncombatants, e.g. civilians

can you see the irony……we are working our ass off to kill these bugs.At th same time some weirdo working in one lab is making bio weapon.

Haematology

White Blood Cells (Leukocytes)

Neutrophils, eosinophils and basophils = granulocytes (polymorphonuclear leukocytes)

Monocytes & lymphocyes = mononuclear

Neutrophils

Most numerous (~60% of WBC)

Nucleus divided into lobes

Cytoplasm contains small granules

Stains pink with Romanowsky dyes

Lifespan of 6-10hrs

Exit into tissues - non-specific defence against bacteria and fungi

Eosinophils

1% of circulating leukocytes 

Large cytoplasmic granules - stain strongly with acidic dye eosin

Nucleus is bilobed

Circulate for 4-5hrs

Exit to tissues –> 

Defence against parasites 

Dampen allergic response

Tissue eosinophils are also capable of responding to bacterial and fungal infection in a similar way to neutrophils.

Basophils

Least numerous (<1%)

Large granules stain strongly with basic dye methylene blue

Involved in anaphylactic hypersensitivity and inflammatory reactions

Monocytes

5% of circulating leukocytes

Large cell

Kidney/clefted shaped nucleus

Scattering of delicate azurophilic granules

Circulate for 10hrs

Mature into phagocytic tissue macrophages

Responsible for the removal of aged RBCs and other debris

Process and present antigens to T-lymphocytes 

(Macrophages are formed in response to an infection or accumulating damaged or dead cells. Large, specialized cells that recognize, engulf and destroy target cells.)

Lymphocytes

Second most common leukocyte (33%)

Much less cytoplasm - nucleus almost fills cell

Variable lifespan

Receptors on surface recognise foreign substances

Several types of lymphocyte - click here

Penicillin

Penicillin is a widely used antibiotic prescribed to treat staphylococci and streptococci bacterial infections. 

beta-lactam family 

Gram-positive bacteria = thick cell walls containing high levels of peptidoglycan

gram-negative bacteria = thinner cell walls with low levels of peptidoglycan and surrounded by a lipopolysaccharide (LPS) layer that prevents antibiotic entry 

penicillin is most effective against gram-positive bacteria where DD-transpeptidase activity is highest.

Examples of penicillins include:

amoxicillin

ampicillin

bacampicillin

oxacillin

penicillin

Mechanism(s)

Penicillin inhibits the bacterial enzyme transpeptidase, responsible for catalysing the final peptidoglycan crosslinking stage of bacterial cell wall synthesis.

Cells wall is weakened and cells swell as water enters and then burst (lysis)

Becomes permanently covalently bonded to the enzymes’s active site (irreversible)

Alternative theory: penicillin mimics D-Ala D-Ala

Or may act as an umbrella inhibitor

Resistance

production of beta-lactamase - destroys the beta-lactam ring of penicillin and makes it ineffective (eg Staphylococcus aureus - most are now resistant)

In response, synthetic penicillin that is resistant to beta-lactamase is in use including egdicloxacillin, oxacillin, nafcillin, and methicillin. 

Some is resistant to methicillin - methicillin-resistant Staphylococcus aureus (MRSA).  

Demonstrating blanket resistance to all beta-lactam antibiotics -extremely serious health risk.

Gram staining

Medically Important Fungi

Antibiotics: Protein Synthesis Inhibitors

Protein Synthesis

Formation of Initiation Complex (tRNA in P site)

aa incoorporation (tRNA in A site, aminoacyl-tRNA)

Formation of Peptide Bond (peptidyltransferase)

Translocation

MNEMONIC: “ALi  eSTá  Cuasi  MAL”

* Inhibit 1: “ALi”

A minoglycosides

Li nezolid

* Inhibit 2: “eSTá”

S treptogramins

T etracyclins

* Inhibit 3: “Cuasi”

C loramphenicol

* Inhibit 4:  "MAL"

M acrolides

A minoglycosides

L incosamides

New background! Download higher quality photo here!

https://drive.google.com/file/d/1F5SlJmB8YiNNtGuKrc-QtMnrrjZ1tOHL/view?usp=sharing

Medically Important Bacteria: Clasification