Jespersen, Alyssa
(2021)
Engineered Cationic Antimicrobial Peptides Differ in Their Ability to Limit in vitro Growth and Viability of Mycobacterium bovis BCG and Mycobacterium tuberculosis.
Master's Thesis, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
Mycobacterium tuberculosis is a major global health concern, causing almost 2 million deaths annually, and the emergence of multidrug resistant strains is a problem in the treatment of infections. Identification of alternatives for traditional antimicrobial treatments for M. tuberculosis infection is vital to combat multidrug resistant strains. Engineered cationic antimicrobial peptides with antibacterial activities may be an alternative to treating bacterial infections like tuberculosis. Here we assessed the bactericidal abilities of three antimicrobial peptides, A4S7, D8, and WLBU2, on two Mycobacterium species and Escherichia coli, a gram-negative bacterium. Bacterial cultures were incubated with varying concentrations of antimicrobial peptides and were assessed through OD measurement at varying times. E. coli was used as a positive control to confirm the peptides were active against a bacterium with a typical gram-negative cell wall, whereas we used M. bovis BCG as a surrogate for M. tuberculosis where we could test the peptides’ activity against the mycobacterial cell wall, which has a more complex structure than other bacteria, under BSL2 conditions. Bactericidal ability and permeability by the peptides were assessed through staining with viability dyes and flow cytometry. We investigated the effect of these peptides on intracellular infection with M. tuberculosis by treating the cells with peptides before and after bacterial infection. All peptides affected the growth of all species, with 4S7 having great bactericidal effects of E. coli growth at the lowest inhibitory concentration. M. tuberculosis and M. bovis were affected by all peptides and experienced permeabilization in the higher concentrations of peptide. Monocyte-derived macrophages from nonhuman primates treated with a4S7 and D8 prior to exposure to M. tuberculosis had fewer bacteria than cells treated after. M. tuberculosis, M. bovis BCG, and E. coli experienced inhibited growth when treated with 10 M or greater of antimicrobial peptides, but little difference was seen during intracellular infection. Our results suggest that engineered cationic antimicrobial peptides are active against M. tuberculosis and our data warrants further investigation into these agents as potential tools for treating the challenging infections caused by mycobacteria.
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Details
Item Type: |
University of Pittsburgh ETD
|
Status: |
Unpublished |
Creators/Authors: |
|
ETD Committee: |
|
Date: |
26 April 2021 |
Defense Date: |
16 April 2021 |
Approval Date: |
18 May 2021 |
Submission Date: |
26 April 2021 |
Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
Number of Pages: |
54 |
Institution: |
University of Pittsburgh |
Schools and Programs: |
School of Public Health > Infectious Diseases and Microbiology |
Degree: |
MS - Master of Science |
Thesis Type: |
Master's Thesis |
Refereed: |
Yes |
Uncontrolled Keywords: |
Mycobacterium tuberculosis, antimicrobial peptides |
Date Deposited: |
18 May 2021 14:33 |
Last Modified: |
18 May 2023 05:15 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/40783 |
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Engineered Cationic Antimicrobial Peptides Differ in Their Ability to Limit in vitro Growth and Viability of Mycobacterium bovis BCG and Mycobacterium tuberculosis. (deposited 18 May 2021 14:33)
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