Targetting pathogen cell surfaces

Question 1

Antibiotics

Answer 1

Specific chemical substances produced by living organisms, or chemically derived from those substances, that are capable of inhibiting the life process of other organisms

Question 2

Penicillins

Answer 2

Affect only bacteria that are actively growing
Kill bacteria - bacteriocidal
Inhibit cell wall synthesis - By inhibition of the transpeptidase that crosslinks polypeotide chains in the cell wall. (inhibition of cell walk construction, irreversible deactivation of enzyme) mimic the D-alanyl-D-alanine reidues that would normalky bind here.

Question 3

Bacterial cell wall (gram positive)

Answer 3

Peptidoglycan cell wall - polymer of glycan units, cross linked by peptides.
DAP with D-alanine peptide cross link gives cell wall strength and structure.

Question 4

Penicillin resistance

Answer 4

Some bacteria express or aquire the enzyme B-lactamase which degrade penicillin.
Onky took 4 years for clinical resistance to arise.
First resistant strains were staphlycoccus aureaus.

Question 5

Carbapenem

Answer 5

Highly resistant to most b-lactamases
Antibiotic of last resort, yet resistance to this class now also being reported.
Bacteria expressing carbapenemases are superbugs.
Gene for NDM-1 can spread from one strain of bacteria to another by horizontal gene transfer.

Question 6

Vancomycin

Answer 6

Antibiotic last resort
Action on gram positive cell walk cross linking
Recognises and binds to the two D-alanine residues on the end of the peptide chains.
Resistance arises when the last D-alanine residue has been replaced with D-lactate, then vancomycin canot bind

Question 7

Streptomycin

Answer 7

First active agent against Tb

Action via inhibition of protein synthesis

Question 8

Limitations of antibiotics

Answer 8

Ineffectiveness against viruses
Ineffective against most protozoan parasites or helminths
Often only effective to a subclass of bacteria
Difficult to synthesize/derivatise
Antibiotic resistance guaranteed.

Question 9

Alternatives to antibiotics?

Answer 9

Antiviral chemotherapy

Example - tamiflu.

Question 10

Neuraminidases

Answer 10

Remove the terminal sialic acid from host cell receptors that bind to the New viron. This promotes the release of the New viron and is essential for the spread of viral infections.
Neuraminidase inhibitors are sialic acid monologues,
Examples are Tamiflu, amantadine.

Question 11

Amantadine

Answer 11

Used both as an antiviral and antiparkinsonism drug.
Inhibits M2 channel which then prevents the release of viral RNA (normally released due to proton influx into viron through M2 channel).

Question 12

HIV

Answer 12

Retrovirus
HIV binds to host CD4 cell receptor via the viral protein gp120. Gp41 ,a viral transmembrane protein, then undergoes a conformational change that assists the fusion of the viral membrane to the host cell membrane.
Currently no cure as viral genome remains integrated in the chromosomes for life.
Drugs active against reverse transcriptase - nucleo side analogues and non-nucleosidal analogues can bind and prevent its action.
Protease inhibitors also used
And peptides that interfere with the CD28-gp41 interaction.
Enfuvirtide binds to gp41, inhibiting the creation of an entry pore for the capsid of the virus, keeping the virus out of the cell.
Meraviroc blocks uptake of HIV by bjndjng to CCR5, the chemokine receptor of macrophages, this prevents binding to gp120:gp41.