Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia

Brandon J H Banaschewski; Edwin J A Veldhuizen; Eleonora Keating; Henk P Haagsman; Yi Y Zuo; Cory M Yamashita; Ruud A W Veldhuizen

doi:10.1128/AAC.04937-14

Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia

Brandon J H Banaschewski, Edwin J A Veldhuizen, Eleonora Keating, Henk P Haagsman, Yi Y Zuo, Cory M Yamashita, Ruud A W Veldhuizen

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Antibiotic resistant bacterial infections represent an emerging health concern in clinical settings, and a lack of novel developments in the pharmaceutical pipeline is creating a "perfect storm" for multi-drug resistant bacterial infections. Antimicrobial peptides (AMPs) have been suggested as future therapeutics for these drug-resistant bacteria, as they have potent broad spectrum activity, with little development of resistance. Due to the unique structure of the lung, bacterial pneumonia has the additional problem of delivering antimicrobials to the site of infection. One potential solution is co-administration of AMPs with exogenous surfactant, allowing for distribution of the peptides to distal airways, and opening of collapsed lung regions.

OBJECTIVE: The objective of this study was to test various surfactant/AMP mixtures with regards to maintaining pulmonary surfactant biophysical properties and bactericidal functions.

METHODS: This study compared the properties of four AMPs (CATH-1, CATH-2, CRAMP, LL-37) suspended in exogenous surfactant (BLES) by assessing surfactant/AMP mixture biophysical and antimicrobial functions. Antimicrobial activity was tested against Methillicin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.

RESULTS: All AMP/surfactant mixtures exhibited an increase of spreading compared to BLES control. BLES+CATH-2 mixtures had no significantly different minimum surface tension versus BLES control. Compared to the other cathelicidins, CATH-2 retained the most bactericidal activity in the presence of BLES.

DISCUSSION: BLES+CATH-2 mixture appears to be an optimal surfactant/AMP mixture based on in vitro assays. Future directions involve investigating the potential of this mixture in animal models of bacterial pneumonia.

Original language	English
Pages (from-to)	3075-3083
Journal	Antimicrobial Agents and Chemotherapy
Volume	59
Issue number	6
DOIs	https://doi.org/10.1128/AAC.04937-14
Publication status	Published - 2015

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10.1128/AAC.04937-14

Antimicrob. Agents Chemother.-2015-Banaschewski-3075-83Final published version, 2.03 MB

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@article{db38c48322fa47a28234b027b32f0b84,

title = "Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia",

abstract = "BACKGROUND: Antibiotic resistant bacterial infections represent an emerging health concern in clinical settings, and a lack of novel developments in the pharmaceutical pipeline is creating a {"}perfect storm{"} for multi-drug resistant bacterial infections. Antimicrobial peptides (AMPs) have been suggested as future therapeutics for these drug-resistant bacteria, as they have potent broad spectrum activity, with little development of resistance. Due to the unique structure of the lung, bacterial pneumonia has the additional problem of delivering antimicrobials to the site of infection. One potential solution is co-administration of AMPs with exogenous surfactant, allowing for distribution of the peptides to distal airways, and opening of collapsed lung regions.OBJECTIVE: The objective of this study was to test various surfactant/AMP mixtures with regards to maintaining pulmonary surfactant biophysical properties and bactericidal functions.METHODS: This study compared the properties of four AMPs (CATH-1, CATH-2, CRAMP, LL-37) suspended in exogenous surfactant (BLES) by assessing surfactant/AMP mixture biophysical and antimicrobial functions. Antimicrobial activity was tested against Methillicin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.RESULTS: All AMP/surfactant mixtures exhibited an increase of spreading compared to BLES control. BLES+CATH-2 mixtures had no significantly different minimum surface tension versus BLES control. Compared to the other cathelicidins, CATH-2 retained the most bactericidal activity in the presence of BLES.DISCUSSION: BLES+CATH-2 mixture appears to be an optimal surfactant/AMP mixture based on in vitro assays. Future directions involve investigating the potential of this mixture in animal models of bacterial pneumonia.",

author = "Banaschewski, {Brandon J H} and Veldhuizen, {Edwin J A} and Eleonora Keating and Haagsman, {Henk P} and Zuo, {Yi Y} and Yamashita, {Cory M} and Veldhuizen, {Ruud A W}",

year = "2015",

doi = "10.1128/AAC.04937-14",

language = "English",

volume = "59",

pages = "3075--3083",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

number = "6",

}

Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia. / Banaschewski, Brandon J H; Veldhuizen, Edwin J A; Keating, Eleonora et al.
In: Antimicrobial Agents and Chemotherapy, Vol. 59, No. 6, 2015, p. 3075-3083.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia

AU - Banaschewski, Brandon J H

AU - Veldhuizen, Edwin J A

AU - Keating, Eleonora

AU - Haagsman, Henk P

AU - Zuo, Yi Y

AU - Yamashita, Cory M

AU - Veldhuizen, Ruud A W

PY - 2015

Y1 - 2015

N2 - BACKGROUND: Antibiotic resistant bacterial infections represent an emerging health concern in clinical settings, and a lack of novel developments in the pharmaceutical pipeline is creating a "perfect storm" for multi-drug resistant bacterial infections. Antimicrobial peptides (AMPs) have been suggested as future therapeutics for these drug-resistant bacteria, as they have potent broad spectrum activity, with little development of resistance. Due to the unique structure of the lung, bacterial pneumonia has the additional problem of delivering antimicrobials to the site of infection. One potential solution is co-administration of AMPs with exogenous surfactant, allowing for distribution of the peptides to distal airways, and opening of collapsed lung regions.OBJECTIVE: The objective of this study was to test various surfactant/AMP mixtures with regards to maintaining pulmonary surfactant biophysical properties and bactericidal functions.METHODS: This study compared the properties of four AMPs (CATH-1, CATH-2, CRAMP, LL-37) suspended in exogenous surfactant (BLES) by assessing surfactant/AMP mixture biophysical and antimicrobial functions. Antimicrobial activity was tested against Methillicin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.RESULTS: All AMP/surfactant mixtures exhibited an increase of spreading compared to BLES control. BLES+CATH-2 mixtures had no significantly different minimum surface tension versus BLES control. Compared to the other cathelicidins, CATH-2 retained the most bactericidal activity in the presence of BLES.DISCUSSION: BLES+CATH-2 mixture appears to be an optimal surfactant/AMP mixture based on in vitro assays. Future directions involve investigating the potential of this mixture in animal models of bacterial pneumonia.

AB - BACKGROUND: Antibiotic resistant bacterial infections represent an emerging health concern in clinical settings, and a lack of novel developments in the pharmaceutical pipeline is creating a "perfect storm" for multi-drug resistant bacterial infections. Antimicrobial peptides (AMPs) have been suggested as future therapeutics for these drug-resistant bacteria, as they have potent broad spectrum activity, with little development of resistance. Due to the unique structure of the lung, bacterial pneumonia has the additional problem of delivering antimicrobials to the site of infection. One potential solution is co-administration of AMPs with exogenous surfactant, allowing for distribution of the peptides to distal airways, and opening of collapsed lung regions.OBJECTIVE: The objective of this study was to test various surfactant/AMP mixtures with regards to maintaining pulmonary surfactant biophysical properties and bactericidal functions.METHODS: This study compared the properties of four AMPs (CATH-1, CATH-2, CRAMP, LL-37) suspended in exogenous surfactant (BLES) by assessing surfactant/AMP mixture biophysical and antimicrobial functions. Antimicrobial activity was tested against Methillicin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.RESULTS: All AMP/surfactant mixtures exhibited an increase of spreading compared to BLES control. BLES+CATH-2 mixtures had no significantly different minimum surface tension versus BLES control. Compared to the other cathelicidins, CATH-2 retained the most bactericidal activity in the presence of BLES.DISCUSSION: BLES+CATH-2 mixture appears to be an optimal surfactant/AMP mixture based on in vitro assays. Future directions involve investigating the potential of this mixture in animal models of bacterial pneumonia.

U2 - 10.1128/AAC.04937-14

DO - 10.1128/AAC.04937-14

M3 - Article

C2 - 25753641

SN - 0066-4804

VL - 59

SP - 3075

EP - 3083

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 6

ER -

Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia

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