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Dissertation Defense Announcement
To:  The George Mason University Community

Candidate: Saira Ahmad Chaudry
Program:    PhD Biosciences

Date:   Monday April 23, 2012
Time:   3:30 p.m.
Place:   George Mason University
             Occoquan Bldg., Room 204
             Prince William campus 
<http://www.gmu.edu/resources/visitors/findex.html>
 
Dissertation Director: Dr. Monique van Hoek
Committee members: Dr. Serguei Popov, Dr. Geraldine Grant, Dr. Barney 
Bishop,

Title: "Regulation of /Francisella novicida/ Biofilm by LL-37 Peptide"


The dissertation is on reserve in the Johnson Center Library, Fairfax 
campus.
The doctoral project will not be read at the meeting, but should be read 
in advance.

All members of the George Mason University community are invited to attend.


*ABSTRACT:
*Biofilms are a natural aggregation of bacterial colonies surrounded by 
an extracellular polymeric matrix that protects the bacteria from 
antibiotic treatments and increases survival compared to planktonic 
bacteria. LL-37 peptide is a human cathelicidin peptide that exhibits 
antimicrobial activity including anti-biofilm activity in gram-negative 
and gram-positive bacteria.  Francisella species are Category A, 
gram-negative, facultative intracellular pathogens resulting in the 
disease of tularemia with as little as 10 bacteria present. Francisella 
has recently shown to form biofilms in vitro.
LL-37 peptide exerts anti-biofilm activity against F. novicida at low 
concentrations of 0.24 g/ml, but its bacterial targets are not known.  
The goal of this research is to identify the unique molecular targets of 
the LL-37 peptide in F. novicida, which may lead to a better 
understanding of the mechanism of action of LL-37 against many bacteria.
Confocal images of F. novicida incubated with 0.24 ?g/ml LL-37 peptide 
for increasing hours have shown a decrease in depth and tightness of 
biofilm formation compared untreated F. novicida biofilm. LL-37 peptide, 
at the aforementioned concentration, also inhibited F. novicida initial 
attachment, which is the first step of biofilm formation. The 
enantiomer, D-LL-37 peptide, also exerted anti-biofilm activity against 
F. novicida.  While the region of anti-biofilm activity of the peptide 
varies depending on the bacterial species, residues 18-37 of LL-37 
peptide have been determined as the region of anti-biofilm activity in 
F. novicida.
LL-37 peptide has been shown to affect many biofilm-associated genes in 
F. novicida.  These include pil assembly proteins, LPS-assembly 
proteins, efflux systems, transferases, and pyruvate synthetase for 
metabolism.  Indeed mutations of these genes have resulted in altered 
biofilm formation.  LL-37 also down regulates expression of response 
regulators kdpE, while up-regulating expression of response regulator 
qseB.  Expression of kdpE normally negatively affects expression of 
qseB.  qseB regulates activation of transcription of many genes that may 
be involved in regulating biofilm formation.  Indeed, many of these 
qseB-regulated genes (such as acetlytransferase, major facilitator 
superfamily (MFS) transporter protein, pyruvate, and hypothetical 
membrane proteins) have been shown to be associated with biofilm 
formation. Identifying the targets of LL-37 peptide in F. novicida has 
helped to understand how the peptide functions in the bacteria to exert 
its anti-biofilm effects.
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