NP108, an Antimicrobial Polymer with Activity against Methicillin- and Mupirocin-Resistant Staphylococcus aureus

Derry K. Mercer; Laura K. Katvars; Fiona Hewitt; Daniel W. Smith; Jennifer Robertson; Carol A. Munro; Deborah A. O'Neil

doi:10.1128/AAC.00502-17

NP108, an Antimicrobial Polymer with Activity against Methicillin- and Mupirocin-Resistant Staphylococcus aureus

Derry K. Mercer, Laura K. Katvars, Fiona Hewitt, Daniel W. Smith, Jennifer Robertson, Carol A. Munro, Deborah A. O'Neil

NOVABIOTICS LTD

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Abstract

Staphylococcus aureusis a clinically significant human pathogen that causes infectious diseases ranging from skin and soft tissue infections (SSTI) and health care-associated infections (HAI) to potentially fatal bacteremia and endocarditis. Nasal carriage ofS. aureus, especially for persistent carriage, is associated with an increased risk of subsequent infection, particularly nosocomial and surgical site infections (SSI), usually via autoinfection. NP108 is a cationic antimicrobial polymer composed of generally recognized as safe (GRAS) amino acid building blocks. NP108 is broad spectrum and rapidly bactericidal (3-log kill in ≤3 h), killing bacteria by membrane disruption and cell lysis. NP108, contrary to many antibiotics, shows equally effective antimicrobial activity against a variety o fS. aureus(MIC100= 8 to 500 mg/liter) and S. epidermidis (MIC100= 4 to 8 mg/liter) isolates, whether exponentially growing or in stationary phase. NP108 is antimicrobially active under nutrient-limiting conditions similar to those found in the anterior nares (MIC100= 8 mg/liter) and kills antibiotic-resilient small colony variants (MIC100= 32 mg/liter) andS. aureusbiofilms (prevention, MIC100= 1 to 4 mg/liter; eradication, MIC100≥ 31.25 mg/liter). NP108 is active against isolates of S. aureusresistant to the current standard-of-care decolonization agent, mupirocin, with no significant increase in the MIC100NP108 is water soluble and has been formulated into compatible aqueous gel vehicles for human use in which antimicrobial efficacy is retained (2.0% [wt/vol]). NP108 is a potential nonantibiotic antimicrobial alternative to antibiotics for the nasal decolonization ofS. aureus, with clear advantages in its mechanism of action over the existing gold standard, mupirocin.

Original language	English
Article number	e00502-17
Pages (from-to)	1-13
Number of pages	13
Journal	Antimicrobial Agents and Chemotherapy
Volume	61
Issue number	9
Early online date	12 Jun 2017
DOIs	https://doi.org/10.1128/AAC.00502-17 https://doi.org/10.1128/AAC.00114-18
Publication status	Published - Sept 2017

Bibliographical note

D.K.M., L.K.K., D.W.S., J.R., and D.A.O. are employees of NovaBiotics Ltd. D.A.O. is a director and shareholder of NovaBiotics Ltd.
D.K.M., L.K.K., F.H., D.W.S., and J.R. carried out the experiments described in the
manuscript. D.K.M., L.K.K., and D.A.O. came up with the ideas and designed the
experiments conducted in the manuscript. D.K.M., D.A.O., and L.K.K. wrote and edited the manuscript. Samples for electron microscopy were prepared by the microscopy and histology facility at the University of Aberdeen.
The work of Laura K. Katvars was partly funded by the Biotechnology
and Biological Sciences Research Council (BBSRC) (1091582). Carol Munro was
supported by the MRC Centre for Medical Mycology (MR/N006364/1).

AUTHOR CORRECTION
Volume 61, no. 9, e00502-17, 2017, https://doi.org/10.1128/AAC.00502-17. Page 1: Carol A. Munro should be added to the list of authors. The updated byline and affiliations are shown above.

Page 11: the last paragraph of Acknowledgments should be replaced with the following sentences. The work of Laura K. Katvars was partly funded by the Biotechnology and Biological Sciences Research Council (BBSRC) (1091582). Carol Munro was supported by the MRC Centre for Medical Mycology (MR/N006364/1).

Copyright © 2018 American Society for Microbiology.

Keywords

Journal Article
antimicrobial activity
nasal decolonization
Staphylococcus aureus

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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NP108, an Antimicrobial Polymer with Activity against Methicillin- and Mupirocin-Resistant Staphylococcus aureus (with correction)
© 2017 Mercer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. https://creativecommons.org/licenses/by/4.0/
Final published version, 2.21 MBLicence: CC BY

Cite this

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abstract = " Staphylococcus aureusis a clinically significant human pathogen that causes infectious diseases ranging from skin and soft tissue infections (SSTI) and health care-associated infections (HAI) to potentially fatal bacteremia and endocarditis. Nasal carriage ofS. aureus, especially for persistent carriage, is associated with an increased risk of subsequent infection, particularly nosocomial and surgical site infections (SSI), usually via autoinfection. NP108 is a cationic antimicrobial polymer composed of generally recognized as safe (GRAS) amino acid building blocks. NP108 is broad spectrum and rapidly bactericidal (3-log kill in ≤3 h), killing bacteria by membrane disruption and cell lysis. NP108, contrary to many antibiotics, shows equally effective antimicrobial activity against a variety o fS. aureus(MIC100= 8 to 500 mg/liter) and S. epidermidis (MIC100= 4 to 8 mg/liter) isolates, whether exponentially growing or in stationary phase. NP108 is antimicrobially active under nutrient-limiting conditions similar to those found in the anterior nares (MIC100= 8 mg/liter) and kills antibiotic-resilient small colony variants (MIC100= 32 mg/liter) andS. aureusbiofilms (prevention, MIC100= 1 to 4 mg/liter; eradication, MIC100≥ 31.25 mg/liter). NP108 is active against isolates of S. aureusresistant to the current standard-of-care decolonization agent, mupirocin, with no significant increase in the MIC100NP108 is water soluble and has been formulated into compatible aqueous gel vehicles for human use in which antimicrobial efficacy is retained (2.0% [wt/vol]). NP108 is a potential nonantibiotic antimicrobial alternative to antibiotics for the nasal decolonization ofS. aureus, with clear advantages in its mechanism of action over the existing gold standard, mupirocin.",

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note = "D.K.M., L.K.K., D.W.S., J.R., and D.A.O. are employees of NovaBiotics Ltd. D.A.O. is a director and shareholder of NovaBiotics Ltd. D.K.M., L.K.K., F.H., D.W.S., and J.R. carried out the experiments described in the manuscript. D.K.M., L.K.K., and D.A.O. came up with the ideas and designed the experiments conducted in the manuscript. D.K.M., D.A.O., and L.K.K. wrote and edited the manuscript. Samples for electron microscopy were prepared by the microscopy and histology facility at the University of Aberdeen. The work of Laura K. Katvars was partly funded by the Biotechnology and Biological Sciences Research Council (BBSRC) (1091582). Carol Munro was supported by the MRC Centre for Medical Mycology (MR/N006364/1). AUTHOR CORRECTION Volume 61, no. 9, e00502-17, 2017, https://doi.org/10.1128/AAC.00502-17. Page 1: Carol A. Munro should be added to the list of authors. The updated byline and affiliations are shown above. Page 11: the last paragraph of Acknowledgments should be replaced with the following sentences. The work of Laura K. Katvars was partly funded by the Biotechnology and Biological Sciences Research Council (BBSRC) (1091582). Carol Munro was supported by the MRC Centre for Medical Mycology (MR/N006364/1). Copyright {\textcopyright} 2018 American Society for Microbiology.",

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AU - Robertson, Jennifer

AU - Munro, Carol A.

AU - O'Neil, Deborah A.

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N2 - Staphylococcus aureusis a clinically significant human pathogen that causes infectious diseases ranging from skin and soft tissue infections (SSTI) and health care-associated infections (HAI) to potentially fatal bacteremia and endocarditis. Nasal carriage ofS. aureus, especially for persistent carriage, is associated with an increased risk of subsequent infection, particularly nosocomial and surgical site infections (SSI), usually via autoinfection. NP108 is a cationic antimicrobial polymer composed of generally recognized as safe (GRAS) amino acid building blocks. NP108 is broad spectrum and rapidly bactericidal (3-log kill in ≤3 h), killing bacteria by membrane disruption and cell lysis. NP108, contrary to many antibiotics, shows equally effective antimicrobial activity against a variety o fS. aureus(MIC100= 8 to 500 mg/liter) and S. epidermidis (MIC100= 4 to 8 mg/liter) isolates, whether exponentially growing or in stationary phase. NP108 is antimicrobially active under nutrient-limiting conditions similar to those found in the anterior nares (MIC100= 8 mg/liter) and kills antibiotic-resilient small colony variants (MIC100= 32 mg/liter) andS. aureusbiofilms (prevention, MIC100= 1 to 4 mg/liter; eradication, MIC100≥ 31.25 mg/liter). NP108 is active against isolates of S. aureusresistant to the current standard-of-care decolonization agent, mupirocin, with no significant increase in the MIC100NP108 is water soluble and has been formulated into compatible aqueous gel vehicles for human use in which antimicrobial efficacy is retained (2.0% [wt/vol]). NP108 is a potential nonantibiotic antimicrobial alternative to antibiotics for the nasal decolonization ofS. aureus, with clear advantages in its mechanism of action over the existing gold standard, mupirocin.

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NP108, an Antimicrobial Polymer with Activity against Methicillin- and Mupirocin-Resistant Staphylococcus aureus

Abstract

Bibliographical note

Keywords

UN SDGs

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