Vancomycin Resistance in Enterococci and Staphylococcus Aureus

Question 1

Describe how peptidoglycan is made

Answer 1

Glucose is converted to amino sugars by lutamine
UDP group added acts as the grlue
Pentapeptide chain added to molecule
C55-undecaprinyl - P -P is a lipid that is added to the peptidoglycan to transport it out of the cell membrane so that it can form the cell wall

Question 2

What is generally one of the last lines of treating gram +ves

Answer 2

Vancomycin

New agents such as linezolid are now also last line

Question 3

What is the diference between how peptidogylcan cross links are made in gram +ve and gram -ve

Answer 3

Gram -ve: direct cross link formed between lysine on the pentapeptide

Gram+ve: crosslink is formed using a glycine residue –> the peptide bond o the D-Ala-D-Ala is borne, this releases energy to form the bond between D-Ala and D-glycine.

Question 4

What are carboxypeptidases

Answer 4

they remove the terminal D-ala to prevent all the peptidoglycan chains becoming cross linked and making the cell wall too rigid

Question 5

Hoes vancomycin work

Answer 5

Binds to the terminal D-ala-D-ala to rpevent cross linking

Question 6

Which organisms if glycopeptide most common in

Answer 6

E. Faecalis
E. Faecium
E. Gallinarium

Resistance is through target site modification!! –> change of the peptidoglycan structure

Question 7

What is the mechanism of Van resistance

Answer 7

Inducible expression of genes that change the target site modification from D-ala-d-ala to d-ala-d-lac or d-ala-d-ser

Question 8

What is the target site in Van A, B and D

Answer 8

D-ala-D-lac

Question 9

What is the target site in Van C, E and F

Answer 9

D-ala-D-ser

Question 10

Which van genes are on plasmids

Answer 10

Van A & B

Question 11

What is the role of Van H

Answer 11

Convert pyruvate to D-Lac

It is a pyruvate dehydrogenase

Question 12

What is the role of Van A

Answer 12

Ligase

Joins D-ala to D-Lac

Question 13

What is the role of Van X

Answer 13

It is a D-D-dipeptidase

It breaks down d-ala-d-ala to d-ala

Question 14

What is the role of Van Y

Answer 14

It is an extra carboxypeptidase –> removes terminal d-ala of any pentapeptides that have been formed to prevent cross linking

This is advantageous as it better to not have cross links that to have vancomycin in the cell wall disturbing its structure

Question 15

What regulates Van expression

Answer 15

Van R and Van S

Question 16

What is the role of Van Z

Answer 16

Mechanism uncear but though to play a role in the differences in ratios of MICs for vancomycin and teicolaninn

Question 17

What drives the intermediate mechanism of resistance in staph aureus

Answer 17

It is population driven

Question 18

What is the mechanism of VISA

Answer 18

Basically increases the cell wall synthesis rate –> increasd thickness of cell wall –> vancomycin binds and more dies

Loss of autolysins and D-D-dipeptidases –> more D-ala-d-ala for vancomycin to bind

Large scale changes in gene expression –> this has a massive fitenss cost for the bacteria hence hVISAs are more successful but arent as resistance

Question 19

When was true VRSA observed

Answer 19

The transfer of Van A occurred in a diabetic foot wound patient who was coinfected with E. Faecalis and S. Auerues –> however this has only happened a few things

Maybe D-Ala-D-lac is a poor substrate for crosslinking in S. Aureus

Or Van A may currently be carried on a plasmid with a high fitness cost to S. Aureus