Ana Bernal Brittany Soto BioQuest Consortium at UTK 17 August 2012 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/nrmicro1795_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.html http://pubs.acs.org/cen/coverstory/83/8325/8325penicillin.html

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.