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

Research output: Contribution to journalArticle

4 Citations (Scopus)
5 Downloads (Pure)

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 languageEnglish
Article numbere00502-17
Pages (from-to)1-13
Number of pages13
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number9
Early online date12 Jun 2017
DOIs
Publication statusPublished - Sep 2017

Fingerprint

Mupirocin
Methicillin-Resistant Staphylococcus aureus
Polymers
Cross Infection
Anti-Bacterial Agents
Nose
Infectious Skin Diseases
Surgical Wound Infection
Soft Tissue Infections
Standard of Care
Bacteremia
Endocarditis
Staphylococcus
Gels
Cell Membrane
Bacteria
Amino Acids
Food
Water

Keywords

  • Journal Article
  • antimicrobial activity
  • nasal decolonization
  • Staphylococcus aureus

Cite this

NP108, an Antimicrobial Polymer with Activity against Methicillin- and Mupirocin-Resistant Staphylococcus aureus. / Mercer, Derry K.; Katvars, Laura K.; Hewitt, Fiona; Smith, Daniel W.; Robertson, Jennifer; Munro, Carol A.; O'Neil, Deborah A.

In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 9, e00502-17, 09.2017, p. 1-13.

Research output: Contribution to journalArticle

Mercer, Derry K. ; Katvars, Laura K. ; Hewitt, Fiona ; Smith, Daniel W. ; Robertson, Jennifer ; Munro, Carol A. ; O'Neil, Deborah A. / NP108, an Antimicrobial Polymer with Activity against Methicillin- and Mupirocin-Resistant Staphylococcus aureus. In: Antimicrobial Agents and Chemotherapy. 2017 ; Vol. 61, No. 9. pp. 1-13.
@article{9940cfde2dbf46cab5cad74dc55f4338,
title = "NP108, an Antimicrobial Polymer with Activity against Methicillin- and Mupirocin-Resistant Staphylococcus aureus",
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.",
keywords = "Journal Article, antimicrobial activity, nasal decolonization, Staphylococcus aureus",
author = "Mercer, {Derry K.} and Katvars, {Laura K.} and Fiona Hewitt and Smith, {Daniel W.} and Jennifer Robertson and Munro, {Carol A.} and O'Neil, {Deborah A.}",
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 {\circledC} 2018 American Society for Microbiology.",
year = "2017",
month = "9",
doi = "10.1128/AAC.00502-17",
language = "English",
volume = "61",
pages = "1--13",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "AMER SOC MICROBIOLOGY",
number = "9",

}

TY - JOUR

T1 - NP108, an Antimicrobial Polymer with Activity against Methicillin- and Mupirocin-Resistant Staphylococcus aureus

AU - Mercer, Derry K.

AU - Katvars, Laura K.

AU - Hewitt, Fiona

AU - Smith, Daniel W.

AU - Robertson, Jennifer

AU - Munro, Carol A.

AU - O'Neil, Deborah A.

N1 - 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.

PY - 2017/9

Y1 - 2017/9

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.

AB - 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.

KW - Journal Article

KW - antimicrobial activity

KW - nasal decolonization

KW - Staphylococcus aureus

U2 - 10.1128/AAC.00502-17

DO - 10.1128/AAC.00502-17

M3 - Article

C2 - 28607014

VL - 61

SP - 1

EP - 13

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 9

M1 - e00502-17

ER -