Visualizing the attack of bacteria by the antimicrobial peptide human defensin 5
Name
959552532-MIT.pdf
Description
Full printable version
Size
28.86 MB
Format
Adobe PDF
Checksum (MD5)
88463d160e689c173d8c91afcf0b6e3b
Author(s)
Chileveru, Haritha Reddy
Advisor(s)
Elizabeth M. Nolan.
Date Issued
2016
Publisher
Massachusetts Institute of Technology
Abstract
Bacterial infections are a major cause of concern in healthcare because of a rise in antibiotic-resistant bacteria and an increase in hospital-acquired infections. In order to combat bacterial infections, we need fundamental understanding of the host-pathogen interaction. As a part of the innate immune response, various organisms, including humans, produce antimicrobial peptides. Human defensin 5 (HD5) is a 32-aa cysteine-rich peptide produced primarily in the small intestine that exhibits broad-spectrum activity against various bacteria, fungi and viruses. In this thesis, in order to study and understand the mechanism of action of HD5, we probed the antibacterial action of HD5 and the bacterial response. We synthesized a family of HD5 analogues with functional modifications including fluorophores. With this toolkit of HD5 derivatives, we examined the effect of HD5 on various bacteria. We demonstrated that HD5ox, the oxidized form of HD5, causes certain distinct morphological changes in Gram-negative bacteria, enters the bacterial cytoplasm and localizes near the cell poles and cell division sites. From these studies we propose that HD5ox overcomes the outer membrane permeability barrier and permeabilizes the inner membrane of Gram-negative bacteria, and it may interact with the cellular targets and interfere with the processes such as cell division. We extended these morphological studies of HD5 0x-treated bacteria and identified certain phenotypic responses in Gram-positive bacteria that further suggest that HD5ox interferes with cellular processes such as cell division.
Description
Thesis: Ph. D. in Biological Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2016.
Cataloged from PDF version of thesis.
Includes bibliographical references.
Subjects
Chemistry.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.
Persistent DSpace Link
