Transcript PBP2a Penicillin Binding Protein

ANA BERNAL
BRITTANY SOTO
BIOQUEST CONSORTIUM AT UTK
17 AUGUST 2012
Cell Wall
 Cell wall is formed by
Peptidoglycan
 Peptidogylcan consists of
repeating polymer sugars
and amino acids.
 Growing peptide chains
are cross linked by
transpeptidase to form a
bilayer.
http://www.nature.com/nrmicro/journal/v6/n1/box/nrmicro
1795_BX3.html
β-Lactam Antibiotics
 Large classification of
antibiotics


Penicillin
Methicillin
 Most commonly used
antibiotics in the past
decade.
http://pubs.acs.org/cen/coverstory/83/8325/8325penicillin.h
tml
PBP Proteins
 β- lactam antibiotics
bind to the cell wall by
PBP proteins
 Prevents transpeptidase
from cross linking
 The cell wall is weakened
and osmotic pressure
forces cell lyses
http://www.pnas.org/content/98/19/10886.full
PBP2a Proteins
 MecA gene produces
PBP2a.
 PBP2a is 78kDa and has
a low affinity to β-lactam
antibiotics
 PBP2a is responsible for
the growing resistance in
Staphylococcus aureus.
Staphlyococcus aureus
 Gram-positive bacteria,
naturally found in the skin
and mucous membranes of
mammals.
 MRSA: Methicillin
resistant strain of S. aureus


Leading acquired
hospitalized infections
In the last 5 years, MRSA has
surpassed the number of
deaths attributed to AIDS.
http://www.health-reply.com/staphylococcus-aureuscommunity-acquired-pneumonia/
S. aureus Resistance to PBP2a
 PBP2a have low affinity
for β- lactam antibiotics
 Allows transpeptidase to
cross link D-alanine with
another peptide chain in
the presence of equal
concentrations of βlactam antibiotics that
would inhibit PBP
proteins
http://www.pnas.org/content/98/19/10886.full
Future Research
 Modifications to β-lactam antibiotics
 Characterization of PBP2a proteins focusing on
kinetic parameters
 Developing a new classification of antibiotics that
target siderophores, low molecular weight, high
affinity iron chelating agents.