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The safe, natural antimicrobial peptide subtilosin for control of bacterial vaginosis
Descriptive
TypeOfResource
Text
TitleInfo
(ID = T-1)
Title
The safe, natural antimicrobial peptide subtilosin for control of bacterial vaginosis
Identifier
ETD_2848
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000056635
Language
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(authority = ISO639-2);
(type = code)
eng
Genre
(authority = marcgt)
theses
Subject
(ID = SBJ-1);
(authority = RUETD)
Topic
Microbiology and Molecular Genetics
Subject
(ID = SBJ-2);
(authority = ETD-LCSH)
Topic
Vagina--Diseases
Subject
(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Vagina--Microbiology
Subject
(ID = SBJ-4);
(authority = ETD-LCSH)
Topic
Bacteriocins
Subject
(ID = SBJ-5);
(authority = ETD-LCSH)
Topic
Anti-infective agents
Abstract
(type = abstract)
Bacterial vaginosis (BV) is a condition characterized by an imbalance in the vaginal microflora where healthy lactobacilli are replaced by anaerobic microorganisms, especially Gardnerella vaginalis. It is estimated that 10-30% of North American women suffer from BV, frequently requiring medical attention. Proliferation of BV-associated organisms is known to have pathogenic effects, particularly in pregnant women. BV is associated with development of pelvic inflammatory disease, low fetal birth weight, preterm births with an elevated risk of infant death, intra-amniotic infections leading to fetal brain damage, and spontaneous abortion. Furthermore, BV (and G. vaginalis in particular) has been shown to increase the probability of contracting HIV and to stimulate viral replication. The antibiotics commonly prescribed to treat BV cause widespread inhibition of the healthy vaginal microflora, leading to a 20% recurrence rate of infection, often with newly developed antibiotic resistance(s). One promising alternative BV treatment is the bacteriocin, or antimicrobial peptide, subtilosin A. This dissertation describes the isolation, characterization, and purification of subtilosin from a fermented dairy product isolate of B. amyloliquefaciens. This is the first report of the intra-species horizontal gene transfer of subtilosin (from B. subtilis), and it is the first bacteriocin characterized from B. amyloliquefaciens. Via well diffusion assays, subtilosin was found to inhibit several human pathogens, including G. vaginalis, but has no effect on healthy vaginal lactobacilli. Motility and structure analyses of human spermatozoa revealed subtilosin possesses potent spermicidal activity. In vitro ectocervical tissue toxicity testing showed subtilosin is completely safe for human tissues. Elucidation of the molecular mechanism of action established that subtilosin specifically inhibits G. vaginalis by forming pores in the cell membrane, causing an efflux of ATP and dissipation of the delta pH portion of the proton motive force. Finally, microplate checkerboard assays confirmed that subtilosin acts synergistically with other antimicrobials of varying mechanisms of action, suggesting that lower concentrations of subtilosin could be used to effectively inhibit G. vaginalis, thereby decreasing the likelihood of developing resistance. Taken together, the data presented herein demonstrate that subtilosin is a safe, natural antimicrobial peptide that can easily be formulated into an effective prophylaxis or treatment for bacterial vaginosis.
PhysicalDescription
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electronic resource
Extent
ix, 159 p. : ill.
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application/pdf
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Note
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Ph.D.
Note
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Includes bibliographical references
Note
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Includes vita
Note
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by Katia Sutyak Noll
Name
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Noll
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Katia Sutyak
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1983-
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author
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Katia Noll
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Chikindas
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Michael
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chair
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Michael Chikindas
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Matthews
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Karl R.
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internal member
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Karl R. Matthews
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Woychik
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Nancy
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Nancy Woychik
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Dedova
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Olga
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outside member
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Advisory Committee
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Olga Dedova
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Rutgers University
Role
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degree grantor
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Graduate School - New Brunswick
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school
OriginInfo
DateCreated
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2010
DateOther
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2010-10
Place
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xx
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Title
Rutgers University Electronic Theses and Dissertations
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ETD
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Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier
(type = doi)
doi:10.7282/T3CN73M1
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
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The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsHolder
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(type = personal)
Name
FamilyName
Noll
GivenName
Katia
Role
Copyright Holder
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Type
Permission or license
DateTime
2010-09-07 13:38:26
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Name
Katia Noll
Affiliation
Rutgers University. Graduate School - New Brunswick
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Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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Technical
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2037760
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