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Evaluation of β- and α/β-peptides as...

Rodriguez Lopez, Angelica de L.

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Evaluation of β- and α/β-peptides as Novel Antimicrobial Agents for Preventing Microbial Biofilms.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Evaluation of β- and α/β-peptides as Novel Antimicrobial Agents for Preventing Microbial Biofilms./
Author:	Rodriguez Lopez, Angelica de L.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	163 p.
Notes:	Source: Dissertations Abstracts International, Volume: 80-08, Section: B.
Contained By:	Dissertations Abstracts International80-08B.
Subject:	Bioengineering. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13427689
ISBN:	9780438842762

Evaluation of β- and α/β-peptides as Novel Antimicrobial Agents for Preventing Microbial Biofilms.
Rodriguez Lopez, Angelica de L.

Evaluation of β- and α/β-peptides as Novel Antimicrobial Agents for Preventing Microbial Biofilms. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 163 p.

Source: Dissertations Abstracts International, Volume: 80-08, Section: B.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2019.

This item must not be sold to any third party vendors.

The work included in this thesis is motivated by the current clinical need for developing new antimicrobial strategies to prevent biofilm-related microbial infections. Here, we first describe our work on evaluating the use of anti-virulence small-molecules for developing combinatorial strategies that reduced the concentrations needed of β-peptidomimetics of antimicrobial α-peptides to prevent C. albicans biofilms (Chapter 2). We identified that combinations with isoamyl alcohol, a C. albicans autoregulatory molecule, improved β-peptide activity by up to 128-fold while causing less than 10% mammalian cell toxicity at concentrations that prevented biofilms. We also evaluated β-peptides effectiveness for preventing clinically-relevant polymicrobial biofilms (Chapter 3). We identified that similar β-peptide concentrations were required for preventing in vitro S. aureus (SA) - C. albicans (CA) polymicrobial biofilms as for preventing monomicrobial biofilms, independently of the containing ratios of S. aureus and C. albicans cells. Furthermore, we demonstrate the prevention of SA-CA polymicrobial biofilms from catheter tube segments by using thin-film-based polymeric coatings embedded with β-peptide. These studies motivate the work performed in the second section directed towards demonstrating the use of β- and α/β-peptide containing polymeric multilayer-based materials for the development of prophylactic strategies to prevent bacterial (Chapter 4) and fungal (Chapter 5) biofilms from titanium and catheter tube surfaces, as prototypes of medical devices susceptible to biofilm-related infections. We used layer-by-layer techniques for the fabrication of β-peptide-containing chitosan and hyaluronic acid thin-films on rough titanium surfaces and our antimicrobial activity results demonstrate we can tune β-peptide loading, by varying β-peptide concentration in loading solutions, to achieve the release β-peptides quantities that prevented S. aureus biofilms but were benign to mammalian cells with osteogenic potential (Chapter 4). Finally, we then describe an approach consisting of poly-L-glutamic acid and poly-L-lysine multilayers for the localized and controlled release of α/β-peptides from catheter surfaces to selectively prevent C. albicans biofilms in vitro and in vivo (Chapter 5). Overall, these studies motivated further development of β- and α/β-peptides as novel antimicrobials and demonstrate the use of materials-based approaches for fabricating antimicrobial coatings on medical devices prone to biofilm-associated infections that could potentially reduce the clinical incidence of microbial infections.

ISBN: 9780438842762Subjects--Topical Terms:

657580
Bioengineering.
Subjects--Index Terms:

Antimicrobial peptides

Evaluation of β- and α/β-peptides as Novel Antimicrobial Agents for Preventing Microbial Biofilms.
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500 $a Source: Dissertations Abstracts International, Volume: 80-08, Section: B.
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520 $a The work included in this thesis is motivated by the current clinical need for developing new antimicrobial strategies to prevent biofilm-related microbial infections. Here, we first describe our work on evaluating the use of anti-virulence small-molecules for developing combinatorial strategies that reduced the concentrations needed of β-peptidomimetics of antimicrobial α-peptides to prevent C. albicans biofilms (Chapter 2). We identified that combinations with isoamyl alcohol, a C. albicans autoregulatory molecule, improved β-peptide activity by up to 128-fold while causing less than 10% mammalian cell toxicity at concentrations that prevented biofilms. We also evaluated β-peptides effectiveness for preventing clinically-relevant polymicrobial biofilms (Chapter 3). We identified that similar β-peptide concentrations were required for preventing in vitro S. aureus (SA) - C. albicans (CA) polymicrobial biofilms as for preventing monomicrobial biofilms, independently of the containing ratios of S. aureus and C. albicans cells. Furthermore, we demonstrate the prevention of SA-CA polymicrobial biofilms from catheter tube segments by using thin-film-based polymeric coatings embedded with β-peptide. These studies motivate the work performed in the second section directed towards demonstrating the use of β- and α/β-peptide containing polymeric multilayer-based materials for the development of prophylactic strategies to prevent bacterial (Chapter 4) and fungal (Chapter 5) biofilms from titanium and catheter tube surfaces, as prototypes of medical devices susceptible to biofilm-related infections. We used layer-by-layer techniques for the fabrication of β-peptide-containing chitosan and hyaluronic acid thin-films on rough titanium surfaces and our antimicrobial activity results demonstrate we can tune β-peptide loading, by varying β-peptide concentration in loading solutions, to achieve the release β-peptides quantities that prevented S. aureus biofilms but were benign to mammalian cells with osteogenic potential (Chapter 4). Finally, we then describe an approach consisting of poly-L-glutamic acid and poly-L-lysine multilayers for the localized and controlled release of α/β-peptides from catheter surfaces to selectively prevent C. albicans biofilms in vitro and in vivo (Chapter 5). Overall, these studies motivated further development of β- and α/β-peptides as novel antimicrobials and demonstrate the use of materials-based approaches for fabricating antimicrobial coatings on medical devices prone to biofilm-associated infections that could potentially reduce the clinical incidence of microbial infections.
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653 $a Thin-films
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