D-enantiomeric antibiofilm peptides effective against anaerobic Cutibacterium acnes biofilm

ABSTRACT The emergence of antibiotic resistance, biofilm formation, and internalization by host cells contribute to a high risk of chronic infections, highlighting the necessity to develop novel therapeutic strategies. Identification of natural host defense peptides (HDPs) with promising antimicrobi...

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Main Authors: Jennifer Varin-Simon, Evan F. Haney, Marius Colin, Frédéric Velard, Sophie C. Gangloff, Robert E. W. Hancock, Fany Reffuveille
Format: Article
Language:English
Published: American Society for Microbiology 2025-05-01
Series:Microbiology Spectrum
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Online Access:https://journals.asm.org/doi/10.1128/spectrum.02523-24
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author Jennifer Varin-Simon
Evan F. Haney
Marius Colin
Frédéric Velard
Sophie C. Gangloff
Robert E. W. Hancock
Fany Reffuveille
author_facet Jennifer Varin-Simon
Evan F. Haney
Marius Colin
Frédéric Velard
Sophie C. Gangloff
Robert E. W. Hancock
Fany Reffuveille
author_sort Jennifer Varin-Simon
collection DOAJ
description ABSTRACT The emergence of antibiotic resistance, biofilm formation, and internalization by host cells contribute to a high risk of chronic infections, highlighting the necessity to develop novel therapeutic strategies. Identification of natural host defense peptides (HDPs) with promising antimicrobial and antibiofilm activities led to the development of synthetic peptides with broad-spectrum efficacy. However, few studies have examined their effect on anaerobic bacterial species. This study aimed to test the effect of synthetic HDPs on Cutibacterium acnes, an anaerobe species involved in 10% of prosthesis joint infections (PJI). A preliminary screen identified three peptides (DJK5, AB009-D, and AB101-D) with promising activity against four C. acnes strains (two of which were isolated from PJI). A bactericidal effect was observed for the three peptides with 50% of planktonic bacteria killing for AB009-D and AB101-D after only 3 hours of contact. DJK5 and AB009-D inhibited the C. acnes adhesion on plastic and titanium supports with a 2-log decrease in bacterial cells. In the presence of peptides, the morphology of C. acnes cells was altered with an increase in cell length observed, especially for one of the non-PJI-related strains. Against mature biofilms, AB101-D was the most effective with an approximate 2-log decrease in adhered CFUs, indicating the induction of bacterial dispersion or death. DJK5 also inhibited C. acnes internalization by osteoblasts, with a reduction of the internalized bacteria quantity for three strains. Overall, this study demonstrates that synthetic HDPs are effective against anaerobic bacteria and hold promise as novel therapeutic candidates to prevent or treat C. acnes PJIs.IMPORTANCEThe emergence of antibiotic tolerance highlights the necessity to develop novel therapeutic strategies with promising antimicrobial but also antibiofilm activities. In this study, we tested the effect of synthetic host defense peptides (HDPs) on Cutibacterium acnes, an anaerobic species, rarely studied, whereas involved in 10% of prosthesis joint infections (PJI). In our study, we demonstrate that the selected synthetic HDPs are effective against this anaerobic bacteria, both as a preventive treatment (effect on planktonic growth, bacterial adhesion, and biofilm formation) and against internalization of C. acnes by osteoblasts, revealing that these peptides are promising as novel therapeutic candidates to prevent or treat C. acnes PJIs.
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spelling doaj-art-e0d0746459bf4d87b50cf85b565eb8292025-08-20T02:14:44ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-05-0113510.1128/spectrum.02523-24D-enantiomeric antibiofilm peptides effective against anaerobic Cutibacterium acnes biofilmJennifer Varin-Simon0Evan F. Haney1Marius Colin2Frédéric Velard3Sophie C. Gangloff4Robert E. W. Hancock5Fany Reffuveille6Université de Reims Champagne-Ardenne, BIOS, Reims, Grand Est, FranceAsep Medical Inc./ABT Innovations Inc., Victoria, British Columbia, CanadaUniversité de Reims Champagne-Ardenne, BIOS, Reims, Grand Est, FranceUniversité de Reims Champagne-Ardenne, BIOS, Reims, Grand Est, FranceUniversité de Reims Champagne-Ardenne, BIOS, Reims, Grand Est, FranceAsep Medical Inc./ABT Innovations Inc., Victoria, British Columbia, CanadaUniversité de Reims Champagne-Ardenne, BIOS, Reims, Grand Est, FranceABSTRACT The emergence of antibiotic resistance, biofilm formation, and internalization by host cells contribute to a high risk of chronic infections, highlighting the necessity to develop novel therapeutic strategies. Identification of natural host defense peptides (HDPs) with promising antimicrobial and antibiofilm activities led to the development of synthetic peptides with broad-spectrum efficacy. However, few studies have examined their effect on anaerobic bacterial species. This study aimed to test the effect of synthetic HDPs on Cutibacterium acnes, an anaerobe species involved in 10% of prosthesis joint infections (PJI). A preliminary screen identified three peptides (DJK5, AB009-D, and AB101-D) with promising activity against four C. acnes strains (two of which were isolated from PJI). A bactericidal effect was observed for the three peptides with 50% of planktonic bacteria killing for AB009-D and AB101-D after only 3 hours of contact. DJK5 and AB009-D inhibited the C. acnes adhesion on plastic and titanium supports with a 2-log decrease in bacterial cells. In the presence of peptides, the morphology of C. acnes cells was altered with an increase in cell length observed, especially for one of the non-PJI-related strains. Against mature biofilms, AB101-D was the most effective with an approximate 2-log decrease in adhered CFUs, indicating the induction of bacterial dispersion or death. DJK5 also inhibited C. acnes internalization by osteoblasts, with a reduction of the internalized bacteria quantity for three strains. Overall, this study demonstrates that synthetic HDPs are effective against anaerobic bacteria and hold promise as novel therapeutic candidates to prevent or treat C. acnes PJIs.IMPORTANCEThe emergence of antibiotic tolerance highlights the necessity to develop novel therapeutic strategies with promising antimicrobial but also antibiofilm activities. In this study, we tested the effect of synthetic host defense peptides (HDPs) on Cutibacterium acnes, an anaerobic species, rarely studied, whereas involved in 10% of prosthesis joint infections (PJI). In our study, we demonstrate that the selected synthetic HDPs are effective against this anaerobic bacteria, both as a preventive treatment (effect on planktonic growth, bacterial adhesion, and biofilm formation) and against internalization of C. acnes by osteoblasts, revealing that these peptides are promising as novel therapeutic candidates to prevent or treat C. acnes PJIs.https://journals.asm.org/doi/10.1128/spectrum.02523-24Cutibacterium acneshost defense peptideprosthesis joint injectionbiofilm
spellingShingle Jennifer Varin-Simon
Evan F. Haney
Marius Colin
Frédéric Velard
Sophie C. Gangloff
Robert E. W. Hancock
Fany Reffuveille
D-enantiomeric antibiofilm peptides effective against anaerobic Cutibacterium acnes biofilm
Microbiology Spectrum
Cutibacterium acnes
host defense peptide
prosthesis joint injection
biofilm
title D-enantiomeric antibiofilm peptides effective against anaerobic Cutibacterium acnes biofilm
title_full D-enantiomeric antibiofilm peptides effective against anaerobic Cutibacterium acnes biofilm
title_fullStr D-enantiomeric antibiofilm peptides effective against anaerobic Cutibacterium acnes biofilm
title_full_unstemmed D-enantiomeric antibiofilm peptides effective against anaerobic Cutibacterium acnes biofilm
title_short D-enantiomeric antibiofilm peptides effective against anaerobic Cutibacterium acnes biofilm
title_sort d enantiomeric antibiofilm peptides effective against anaerobic cutibacterium acnes biofilm
topic Cutibacterium acnes
host defense peptide
prosthesis joint injection
biofilm
url https://journals.asm.org/doi/10.1128/spectrum.02523-24
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