A N A B E R N A L B R I T T A N Y S O T O B I O Q U E S T C O N S O R T I U M A T U T K 1 7 A U G U S T 2 0 1 2

 Cell wall is formed by Peptidoglycan

Cell Wall

 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

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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-aureus community-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 β lactam 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.