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RNA polymerase inhibitor activity against Staphylococcus epidermidis biofilms

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TitleInfo
Title
RNA polymerase inhibitor activity against Staphylococcus epidermidis biofilms
Name (type = personal)
NamePart (type = family)
Ho
NamePart (type = given)
Seanghuoy
NamePart (type = date)
1989-
DisplayForm
Seanghuoy Ho
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Ebright
NamePart (type = given)
Richard H.
DisplayForm
Richard H. Ebright
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Chikindas
NamePart (type = given)
Michael L.
DisplayForm
Michael L. Chikindas
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Nickels
NamePart (type = given)
Bryce E.
DisplayForm
Bryce E. Nickels
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2014
DateOther (qualifier = exact); (type = degree)
2014-05
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Biofilms were defined as the structural phenotype of microbial communities enclosed in the self-produced polymeric matrix mainly composed of extracellular polysaccharides (EPS). S.epidermidis is associated with chronic diseases involving implant medical devices due to its strong ability to form biofilms and they are difficult to eradicate. Rifampin, one of the most active antibiotics used to treat biofilm-associated infections, is a bacterial RNA polymerase (RNAP) inhibitor; however strong bacterial resistance to this drug leads to the need to find more active compounds acting at the same target: bacterial RNAP. In this study, I test whether other bacterial RNAP inhibitors are also active against S.epidermidis biofilms by determining their Minimum Biofilm Eradication Concentration (MBEC) as compared to those of antibiotics functioning through target other than bacterial RNAP (reference antibiotics). Two biofilm assays were used: MBEC P&G assay using Calgary Biofilm device (peg assay) and glass biofilm assay. In the peg assay, biofilm density of 6 log10 of cfu/peg was obtained and used for biofilm susceptibility testing. In addition to Rifampin, three novel synthesized bacterial RNAP inhibitors were found to be more effective in completely eradicate S.epidermidis biofilms in vitro: 3RHTK27, 3RHTK44 and OMTK13 with MBEC value of 25µg/ml, 12.5µg/ml and 50µg/ml, respectively. None of the other antibiotics were able to eradicate S.epidermidis biofilms (MBEC > 400µg/ml). These three RNAP inhibitors were also found to be effective in glass biofilm assay having MBEC values of 6.25µg/ml, 3.125µg/ml and 25µg/ml, respectively. These three compounds are interesting candidates for further development as antibacterial and anti-biofilm agents. Not all RNAP inhibitors which are active against planktonic cells are active against S.epidermidis biofilms. Nevertheless, seeing the same pattern of result from two different assays that reference antibiotics tested were not capable of eradicating biofilms while three out of eleven bacterial RNAP inhibitors tested were active is encouraging and suggesting that RNAP makes a good target for finding drugs to treat biofilm-related diseases.
Subject (authority = RUETD)
Topic
Microbial Biology
Subject (authority = ETD-LCSH)
Topic
Biofilms
Subject (authority = ETD-LCSH)
Topic
Antibiotics--Analysis
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_5415
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
ix, 54 p. : ill.
Note (type = degree)
M.S.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Seanghuoy Ho
Subject (authority = ETD-LCSH)
Topic
Staphylococcal infections--Treatment
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T36W98D1
Genre (authority = ExL-Esploro)
ETD graduate
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Ho
GivenName
Seanghuoy
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (point = start); (qualifier = exact)
2014-04-09 09:51:50
AssociatedEntity
Name
Seanghuoy Ho
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
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.
RightsEvent
Type
Embargo
DateTime (encoding = w3cdtf); (keyDate = no); (point = start); (qualifier = exact)
2014-07-23
DateTime (encoding = w3cdtf); (keyDate = no); (point = end); (qualifier = exact)
2016-05-31
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 31, 2016.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical

RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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