In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents

Ann M. Czyzewski, Håvard Jenssen, Christopher D. Fjell, M. Waldbrook, Nathaniel P. Chongsiriwatana, Eddie Yuen, Robert E. W. Hancock, Annelise E. Barron

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Bacterial resistance to conventional antibiotics is a global threat that has spurred the development of antimicrobial peptides (AMPs) and their mimetics as novel anti-infective agents. While the bioavailability of AMPs is often reduced due to protease activity, the non-natural structure of AMP mimetics renders them robust to proteolytic degradation, thus offering a distinct advantage for their clinical application. We explore the therapeutic potential of N-substituted glycines, or peptoids, as AMP mimics using a multi-faceted approach that includes in silico, in vitro, and in vivo techniques. We report a new QSAR model that we developed based on 27 diverse peptoid sequences, which accurately correlates antimicrobial peptoid structure with antimicrobial activity. We have identified a number of peptoids that have potent, broad-spectrum in vitro activity against multi-drug resistant bacterial strains. Lastly, using a murine model of invasive S. aureus infection, we demonstrate that one of the best candidate peptoids at 4 mg/kg significantly reduces with a two-log order the bacterial counts compared with saline-treated controls. Taken together, our results demonstrate the promising therapeutic potential of peptoids as antimicrobial agents.
OriginalsprogEngelsk
Artikelnummere0135961
TidsskriftP L o S One
Vol/bind11
Udgave nummer2
ISSN1932-6203
DOI
StatusUdgivet - 2016

Citer dette

Czyzewski, A. M., Jenssen, H., Fjell, C. D., Waldbrook, M., Chongsiriwatana, N. P., Yuen, E., ... Barron, A. E. (2016). In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents. P L o S One, 11(2), [e0135961]. https://doi.org/10.1371/journal.pone.0135961
Czyzewski, Ann M. ; Jenssen, Håvard ; Fjell, Christopher D. ; Waldbrook, M. ; Chongsiriwatana, Nathaniel P. ; Yuen, Eddie ; Hancock, Robert E. W. ; Barron, Annelise E. / In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents. I: P L o S One. 2016 ; Bind 11, Nr. 2.
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title = "In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents",
abstract = "Bacterial resistance to conventional antibiotics is a global threat that has spurred the development of antimicrobial peptides (AMPs) and their mimetics as novel anti-infective agents. While the bioavailability of AMPs is often reduced due to protease activity, the non-natural structure of AMP mimetics renders them robust to proteolytic degradation, thus offering a distinct advantage for their clinical application. We explore the therapeutic potential of N-substituted glycines, or peptoids, as AMP mimics using a multi-faceted approach that includes in silico, in vitro, and in vivo techniques. We report a new QSAR model that we developed based on 27 diverse peptoid sequences, which accurately correlates antimicrobial peptoid structure with antimicrobial activity. We have identified a number of peptoids that have potent, broad-spectrum in vitro activity against multi-drug resistant bacterial strains. Lastly, using a murine model of invasive S. aureus infection, we demonstrate that one of the best candidate peptoids at 4 mg/kg significantly reduces with a two-log order the bacterial counts compared with saline-treated controls. Taken together, our results demonstrate the promising therapeutic potential of peptoids as antimicrobial agents.",
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Czyzewski, AM, Jenssen, H, Fjell, CD, Waldbrook, M, Chongsiriwatana, NP, Yuen, E, Hancock, REW & Barron, AE 2016, 'In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents', P L o S One, bind 11, nr. 2, e0135961. https://doi.org/10.1371/journal.pone.0135961

In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents. / Czyzewski, Ann M.; Jenssen, Håvard; Fjell, Christopher D.; Waldbrook, M.; Chongsiriwatana, Nathaniel P.; Yuen, Eddie; Hancock, Robert E. W.; Barron, Annelise E.

I: P L o S One, Bind 11, Nr. 2, e0135961, 2016.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents

AU - Czyzewski, Ann M.

AU - Jenssen, Håvard

AU - Fjell, Christopher D.

AU - Waldbrook, M.

AU - Chongsiriwatana, Nathaniel P.

AU - Yuen, Eddie

AU - Hancock, Robert E. W.

AU - Barron, Annelise E.

PY - 2016

Y1 - 2016

N2 - Bacterial resistance to conventional antibiotics is a global threat that has spurred the development of antimicrobial peptides (AMPs) and their mimetics as novel anti-infective agents. While the bioavailability of AMPs is often reduced due to protease activity, the non-natural structure of AMP mimetics renders them robust to proteolytic degradation, thus offering a distinct advantage for their clinical application. We explore the therapeutic potential of N-substituted glycines, or peptoids, as AMP mimics using a multi-faceted approach that includes in silico, in vitro, and in vivo techniques. We report a new QSAR model that we developed based on 27 diverse peptoid sequences, which accurately correlates antimicrobial peptoid structure with antimicrobial activity. We have identified a number of peptoids that have potent, broad-spectrum in vitro activity against multi-drug resistant bacterial strains. Lastly, using a murine model of invasive S. aureus infection, we demonstrate that one of the best candidate peptoids at 4 mg/kg significantly reduces with a two-log order the bacterial counts compared with saline-treated controls. Taken together, our results demonstrate the promising therapeutic potential of peptoids as antimicrobial agents.

AB - Bacterial resistance to conventional antibiotics is a global threat that has spurred the development of antimicrobial peptides (AMPs) and their mimetics as novel anti-infective agents. While the bioavailability of AMPs is often reduced due to protease activity, the non-natural structure of AMP mimetics renders them robust to proteolytic degradation, thus offering a distinct advantage for their clinical application. We explore the therapeutic potential of N-substituted glycines, or peptoids, as AMP mimics using a multi-faceted approach that includes in silico, in vitro, and in vivo techniques. We report a new QSAR model that we developed based on 27 diverse peptoid sequences, which accurately correlates antimicrobial peptoid structure with antimicrobial activity. We have identified a number of peptoids that have potent, broad-spectrum in vitro activity against multi-drug resistant bacterial strains. Lastly, using a murine model of invasive S. aureus infection, we demonstrate that one of the best candidate peptoids at 4 mg/kg significantly reduces with a two-log order the bacterial counts compared with saline-treated controls. Taken together, our results demonstrate the promising therapeutic potential of peptoids as antimicrobial agents.

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DO - 10.1371/journal.pone.0135961

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JO - P L o S One

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SN - 1932-6203

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ER -