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Novel engineered cationic antimicrobial peptides have a broad-spectrum activity against: Francisella tularensis, burkholderia pseudomalli and yersinia pestis

Abdelbaqi, Suha (2014) Novel engineered cationic antimicrobial peptides have a broad-spectrum activity against: Francisella tularensis, burkholderia pseudomalli and yersinia pestis. Master's Thesis, University of Pittsburgh. (Unpublished)

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Broad spectrum antimicrobial activity against biodefense pathogens is highly desirable as a delay in treatment of infection with these pathogens can be fatal. Engineered cationic antimicrobial peptides (eCAPs) are de novo synthesized amphipathic agents with broad spectrum activities against gram-positive and gram-negative bacteria including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). We evaluated eCAPs designated as WLBU2 and WR12 against three bacterial pathogens that are considered potential biological weapons and a great public health concern. Using both bacterial killing and growth inhibition assays, different concentrations of WLBU2 and WR12 were tested in vitro against Francisella tularensis, Burkholderia pseudomallei, and Yersinia pestis. LL37, a natural mammalian antimicrobial peptide was used for comparison. WLBU2 proved to be the best candidate against F. tularensis with a single dose of 3μM needed to achieve a 90% reduction in bacterial count and a minimum inhibitory concentration (MIC) of 25 μM. LL37 failed to achieve more than 8% reduction in the bacterial count of F. tularensis with concentrations up to 100 µM. Both WLBU2 and WR12 achieved significantly better results against Y. pestis compared to LL37, but only WR12 was able to attain a MBC of 50 μM. Results for B. pseudomallei varied depending on the testing environment; a substantial reduction in bacterial count was seen with WLBU2 in potassium phosphate buffer but not in phosphate buffered saline. WLBU3 and WLBU4 were also tested against B. pseudomallei and results indicate that increasing the length of the peptides did not enhance their activity against B. pseudomallei. Moreover, WLBU2 was tested against Francisella tularensis (SchuS4) infected macrophage cells (J774) and found to decrease intracellular bacterial count by more than 90% at a concentration of 12.5µM. This data demonstrates the potential usefulness of eCAPs against the three pathogens that were evaluated and the broad applicability of eCAPs, particularly WLBU2, against bacterial biodefense pathogens.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Abdelbaqi, Suhasua12@pitt.eduSUA12
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorReed, Douglas Sdsreed@pitt.eduDSREED
Committee MemberHartman, Amy
Committee MemberMontelaro, Ronald Crmont@pitt.eduRMONT
Committee MemberReinhart, Todd A.reinhar@pitt.eduREINHAR
Date: 29 September 2014
Date Type: Publication
Defense Date: 13 June 2014
Approval Date: 29 September 2014
Submission Date: 4 June 2014
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 67
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Evaluation of antimicrobial activity of eCAPs against biodefense pathogens
Date Deposited: 29 Sep 2014 21:23
Last Modified: 15 Nov 2016 14:20


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