Novel Antibacterial Agents SAAP-148 and Halicin Combat Gram-Negative Bacteria Colonizing Catheters
The antibiotic management of catheter-related infections (CRIs) often fails owing to the emergence of antimicrobial-resistant strains and/or biofilm/persister apparitions. Thus, we investigated the efficacy of two novel antimicrobial agents, i.e., the synthetic peptide SAAP-148 and the novel antibio...
Ausführliche Beschreibung
Autor*in: |
Nesrine Bouhrour [verfasserIn] Tanny J. K. van der Reijden [verfasserIn] Michella M. Voet [verfasserIn] Bep Schonkeren-Ravensbergen [verfasserIn] Robert A. Cordfunke [verfasserIn] Jan Wouter Drijfhout [verfasserIn] Farida Bendali [verfasserIn] Peter H. Nibbering [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2023 |
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Übergeordnetes Werk: |
In: Antibiotics - MDPI AG, 2013, 12(2023), 12, p 1743 |
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Übergeordnetes Werk: |
volume:12 ; year:2023 ; number:12, p 1743 |
Links: |
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DOI / URN: |
10.3390/antibiotics12121743 |
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Katalog-ID: |
DOAJ098921215 |
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10.3390/antibiotics12121743 doi (DE-627)DOAJ098921215 (DE-599)DOAJaf0519dbe2154ec59334aa1c7d95c655 DE-627 ger DE-627 rakwb eng RM1-950 Nesrine Bouhrour verfasserin aut Novel Antibacterial Agents SAAP-148 and Halicin Combat Gram-Negative Bacteria Colonizing Catheters 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The antibiotic management of catheter-related infections (CRIs) often fails owing to the emergence of antimicrobial-resistant strains and/or biofilm/persister apparitions. Thus, we investigated the efficacy of two novel antimicrobial agents, i.e., the synthetic peptide SAAP-148 and the novel antibiotic halicin, against Gram-negative bacteria (GNB) colonizing catheters. The antibacterial, anti-biofilm, and anti-persister activities of both agents were evaluated against <i<Acinetobacter baumannii</i<, <i<Escherichia coli</i<, and <i<Klebsiella pneumoniae</i< strains. The enrolled strains were isolated from catheters and selected based on their resistance to at least three antibiotic classes and biofilm formation potential. Furthermore, the hemolysis and endotoxin neutralization abilities of these agents were explored. The bactericidal activity of both agents was reduced in urine and plasma as compared to buffered saline. In a dose-dependent manner, SAAP-148 and halicin reduced bacterial counts in 24 h preformed biofilms on silicone elastomer discs and eliminated persisters originating from antibiotic-exposed mature 7-day biofilms, with halicin being less effective than SAAP-148. Importantly, SAAP-148 and halicin acted synergistically on <i<E. coli</i< and <i<K. pneumoniae</i< biofilms but not on <i<A. baumannii</i< biofilms. The peptide, but not halicin, decreased the production of IL-12p40 upon exposure to UV-killed bacteria. This preliminary study showed that SAAP-148 and halicin alone/in combination are promising candidates to fight GNB colonizing catheters. catheter antibiotic resistance biofilm persisters halicin SAAP-148 Therapeutics. Pharmacology Tanny J. K. van der Reijden verfasserin aut Michella M. Voet verfasserin aut Bep Schonkeren-Ravensbergen verfasserin aut Robert A. Cordfunke verfasserin aut Jan Wouter Drijfhout verfasserin aut Farida Bendali verfasserin aut Peter H. Nibbering verfasserin aut In Antibiotics MDPI AG, 2013 12(2023), 12, p 1743 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:12 year:2023 number:12, p 1743 https://doi.org/10.3390/antibiotics12121743 kostenfrei https://doaj.org/article/af0519dbe2154ec59334aa1c7d95c655 kostenfrei https://www.mdpi.com/2079-6382/12/12/1743 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 12, p 1743 |
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10.3390/antibiotics12121743 doi (DE-627)DOAJ098921215 (DE-599)DOAJaf0519dbe2154ec59334aa1c7d95c655 DE-627 ger DE-627 rakwb eng RM1-950 Nesrine Bouhrour verfasserin aut Novel Antibacterial Agents SAAP-148 and Halicin Combat Gram-Negative Bacteria Colonizing Catheters 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The antibiotic management of catheter-related infections (CRIs) often fails owing to the emergence of antimicrobial-resistant strains and/or biofilm/persister apparitions. Thus, we investigated the efficacy of two novel antimicrobial agents, i.e., the synthetic peptide SAAP-148 and the novel antibiotic halicin, against Gram-negative bacteria (GNB) colonizing catheters. The antibacterial, anti-biofilm, and anti-persister activities of both agents were evaluated against <i<Acinetobacter baumannii</i<, <i<Escherichia coli</i<, and <i<Klebsiella pneumoniae</i< strains. The enrolled strains were isolated from catheters and selected based on their resistance to at least three antibiotic classes and biofilm formation potential. Furthermore, the hemolysis and endotoxin neutralization abilities of these agents were explored. The bactericidal activity of both agents was reduced in urine and plasma as compared to buffered saline. In a dose-dependent manner, SAAP-148 and halicin reduced bacterial counts in 24 h preformed biofilms on silicone elastomer discs and eliminated persisters originating from antibiotic-exposed mature 7-day biofilms, with halicin being less effective than SAAP-148. Importantly, SAAP-148 and halicin acted synergistically on <i<E. coli</i< and <i<K. pneumoniae</i< biofilms but not on <i<A. baumannii</i< biofilms. The peptide, but not halicin, decreased the production of IL-12p40 upon exposure to UV-killed bacteria. This preliminary study showed that SAAP-148 and halicin alone/in combination are promising candidates to fight GNB colonizing catheters. catheter antibiotic resistance biofilm persisters halicin SAAP-148 Therapeutics. Pharmacology Tanny J. K. van der Reijden verfasserin aut Michella M. Voet verfasserin aut Bep Schonkeren-Ravensbergen verfasserin aut Robert A. Cordfunke verfasserin aut Jan Wouter Drijfhout verfasserin aut Farida Bendali verfasserin aut Peter H. Nibbering verfasserin aut In Antibiotics MDPI AG, 2013 12(2023), 12, p 1743 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:12 year:2023 number:12, p 1743 https://doi.org/10.3390/antibiotics12121743 kostenfrei https://doaj.org/article/af0519dbe2154ec59334aa1c7d95c655 kostenfrei https://www.mdpi.com/2079-6382/12/12/1743 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 12, p 1743 |
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10.3390/antibiotics12121743 doi (DE-627)DOAJ098921215 (DE-599)DOAJaf0519dbe2154ec59334aa1c7d95c655 DE-627 ger DE-627 rakwb eng RM1-950 Nesrine Bouhrour verfasserin aut Novel Antibacterial Agents SAAP-148 and Halicin Combat Gram-Negative Bacteria Colonizing Catheters 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The antibiotic management of catheter-related infections (CRIs) often fails owing to the emergence of antimicrobial-resistant strains and/or biofilm/persister apparitions. Thus, we investigated the efficacy of two novel antimicrobial agents, i.e., the synthetic peptide SAAP-148 and the novel antibiotic halicin, against Gram-negative bacteria (GNB) colonizing catheters. The antibacterial, anti-biofilm, and anti-persister activities of both agents were evaluated against <i<Acinetobacter baumannii</i<, <i<Escherichia coli</i<, and <i<Klebsiella pneumoniae</i< strains. The enrolled strains were isolated from catheters and selected based on their resistance to at least three antibiotic classes and biofilm formation potential. Furthermore, the hemolysis and endotoxin neutralization abilities of these agents were explored. The bactericidal activity of both agents was reduced in urine and plasma as compared to buffered saline. In a dose-dependent manner, SAAP-148 and halicin reduced bacterial counts in 24 h preformed biofilms on silicone elastomer discs and eliminated persisters originating from antibiotic-exposed mature 7-day biofilms, with halicin being less effective than SAAP-148. Importantly, SAAP-148 and halicin acted synergistically on <i<E. coli</i< and <i<K. pneumoniae</i< biofilms but not on <i<A. baumannii</i< biofilms. The peptide, but not halicin, decreased the production of IL-12p40 upon exposure to UV-killed bacteria. This preliminary study showed that SAAP-148 and halicin alone/in combination are promising candidates to fight GNB colonizing catheters. catheter antibiotic resistance biofilm persisters halicin SAAP-148 Therapeutics. Pharmacology Tanny J. K. van der Reijden verfasserin aut Michella M. Voet verfasserin aut Bep Schonkeren-Ravensbergen verfasserin aut Robert A. Cordfunke verfasserin aut Jan Wouter Drijfhout verfasserin aut Farida Bendali verfasserin aut Peter H. Nibbering verfasserin aut In Antibiotics MDPI AG, 2013 12(2023), 12, p 1743 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:12 year:2023 number:12, p 1743 https://doi.org/10.3390/antibiotics12121743 kostenfrei https://doaj.org/article/af0519dbe2154ec59334aa1c7d95c655 kostenfrei https://www.mdpi.com/2079-6382/12/12/1743 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 12, p 1743 |
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10.3390/antibiotics12121743 doi (DE-627)DOAJ098921215 (DE-599)DOAJaf0519dbe2154ec59334aa1c7d95c655 DE-627 ger DE-627 rakwb eng RM1-950 Nesrine Bouhrour verfasserin aut Novel Antibacterial Agents SAAP-148 and Halicin Combat Gram-Negative Bacteria Colonizing Catheters 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The antibiotic management of catheter-related infections (CRIs) often fails owing to the emergence of antimicrobial-resistant strains and/or biofilm/persister apparitions. Thus, we investigated the efficacy of two novel antimicrobial agents, i.e., the synthetic peptide SAAP-148 and the novel antibiotic halicin, against Gram-negative bacteria (GNB) colonizing catheters. The antibacterial, anti-biofilm, and anti-persister activities of both agents were evaluated against <i<Acinetobacter baumannii</i<, <i<Escherichia coli</i<, and <i<Klebsiella pneumoniae</i< strains. The enrolled strains were isolated from catheters and selected based on their resistance to at least three antibiotic classes and biofilm formation potential. Furthermore, the hemolysis and endotoxin neutralization abilities of these agents were explored. The bactericidal activity of both agents was reduced in urine and plasma as compared to buffered saline. In a dose-dependent manner, SAAP-148 and halicin reduced bacterial counts in 24 h preformed biofilms on silicone elastomer discs and eliminated persisters originating from antibiotic-exposed mature 7-day biofilms, with halicin being less effective than SAAP-148. Importantly, SAAP-148 and halicin acted synergistically on <i<E. coli</i< and <i<K. pneumoniae</i< biofilms but not on <i<A. baumannii</i< biofilms. The peptide, but not halicin, decreased the production of IL-12p40 upon exposure to UV-killed bacteria. This preliminary study showed that SAAP-148 and halicin alone/in combination are promising candidates to fight GNB colonizing catheters. catheter antibiotic resistance biofilm persisters halicin SAAP-148 Therapeutics. Pharmacology Tanny J. K. van der Reijden verfasserin aut Michella M. Voet verfasserin aut Bep Schonkeren-Ravensbergen verfasserin aut Robert A. Cordfunke verfasserin aut Jan Wouter Drijfhout verfasserin aut Farida Bendali verfasserin aut Peter H. Nibbering verfasserin aut In Antibiotics MDPI AG, 2013 12(2023), 12, p 1743 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:12 year:2023 number:12, p 1743 https://doi.org/10.3390/antibiotics12121743 kostenfrei https://doaj.org/article/af0519dbe2154ec59334aa1c7d95c655 kostenfrei https://www.mdpi.com/2079-6382/12/12/1743 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 12, p 1743 |
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10.3390/antibiotics12121743 doi (DE-627)DOAJ098921215 (DE-599)DOAJaf0519dbe2154ec59334aa1c7d95c655 DE-627 ger DE-627 rakwb eng RM1-950 Nesrine Bouhrour verfasserin aut Novel Antibacterial Agents SAAP-148 and Halicin Combat Gram-Negative Bacteria Colonizing Catheters 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The antibiotic management of catheter-related infections (CRIs) often fails owing to the emergence of antimicrobial-resistant strains and/or biofilm/persister apparitions. Thus, we investigated the efficacy of two novel antimicrobial agents, i.e., the synthetic peptide SAAP-148 and the novel antibiotic halicin, against Gram-negative bacteria (GNB) colonizing catheters. The antibacterial, anti-biofilm, and anti-persister activities of both agents were evaluated against <i<Acinetobacter baumannii</i<, <i<Escherichia coli</i<, and <i<Klebsiella pneumoniae</i< strains. The enrolled strains were isolated from catheters and selected based on their resistance to at least three antibiotic classes and biofilm formation potential. Furthermore, the hemolysis and endotoxin neutralization abilities of these agents were explored. The bactericidal activity of both agents was reduced in urine and plasma as compared to buffered saline. In a dose-dependent manner, SAAP-148 and halicin reduced bacterial counts in 24 h preformed biofilms on silicone elastomer discs and eliminated persisters originating from antibiotic-exposed mature 7-day biofilms, with halicin being less effective than SAAP-148. Importantly, SAAP-148 and halicin acted synergistically on <i<E. coli</i< and <i<K. pneumoniae</i< biofilms but not on <i<A. baumannii</i< biofilms. The peptide, but not halicin, decreased the production of IL-12p40 upon exposure to UV-killed bacteria. This preliminary study showed that SAAP-148 and halicin alone/in combination are promising candidates to fight GNB colonizing catheters. catheter antibiotic resistance biofilm persisters halicin SAAP-148 Therapeutics. Pharmacology Tanny J. K. van der Reijden verfasserin aut Michella M. Voet verfasserin aut Bep Schonkeren-Ravensbergen verfasserin aut Robert A. Cordfunke verfasserin aut Jan Wouter Drijfhout verfasserin aut Farida Bendali verfasserin aut Peter H. Nibbering verfasserin aut In Antibiotics MDPI AG, 2013 12(2023), 12, p 1743 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:12 year:2023 number:12, p 1743 https://doi.org/10.3390/antibiotics12121743 kostenfrei https://doaj.org/article/af0519dbe2154ec59334aa1c7d95c655 kostenfrei https://www.mdpi.com/2079-6382/12/12/1743 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 12, p 1743 |
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Novel Antibacterial Agents SAAP-148 and Halicin Combat Gram-Negative Bacteria Colonizing Catheters |
abstract |
The antibiotic management of catheter-related infections (CRIs) often fails owing to the emergence of antimicrobial-resistant strains and/or biofilm/persister apparitions. Thus, we investigated the efficacy of two novel antimicrobial agents, i.e., the synthetic peptide SAAP-148 and the novel antibiotic halicin, against Gram-negative bacteria (GNB) colonizing catheters. The antibacterial, anti-biofilm, and anti-persister activities of both agents were evaluated against <i<Acinetobacter baumannii</i<, <i<Escherichia coli</i<, and <i<Klebsiella pneumoniae</i< strains. The enrolled strains were isolated from catheters and selected based on their resistance to at least three antibiotic classes and biofilm formation potential. Furthermore, the hemolysis and endotoxin neutralization abilities of these agents were explored. The bactericidal activity of both agents was reduced in urine and plasma as compared to buffered saline. In a dose-dependent manner, SAAP-148 and halicin reduced bacterial counts in 24 h preformed biofilms on silicone elastomer discs and eliminated persisters originating from antibiotic-exposed mature 7-day biofilms, with halicin being less effective than SAAP-148. Importantly, SAAP-148 and halicin acted synergistically on <i<E. coli</i< and <i<K. pneumoniae</i< biofilms but not on <i<A. baumannii</i< biofilms. The peptide, but not halicin, decreased the production of IL-12p40 upon exposure to UV-killed bacteria. This preliminary study showed that SAAP-148 and halicin alone/in combination are promising candidates to fight GNB colonizing catheters. |
abstractGer |
The antibiotic management of catheter-related infections (CRIs) often fails owing to the emergence of antimicrobial-resistant strains and/or biofilm/persister apparitions. Thus, we investigated the efficacy of two novel antimicrobial agents, i.e., the synthetic peptide SAAP-148 and the novel antibiotic halicin, against Gram-negative bacteria (GNB) colonizing catheters. The antibacterial, anti-biofilm, and anti-persister activities of both agents were evaluated against <i<Acinetobacter baumannii</i<, <i<Escherichia coli</i<, and <i<Klebsiella pneumoniae</i< strains. The enrolled strains were isolated from catheters and selected based on their resistance to at least three antibiotic classes and biofilm formation potential. Furthermore, the hemolysis and endotoxin neutralization abilities of these agents were explored. The bactericidal activity of both agents was reduced in urine and plasma as compared to buffered saline. In a dose-dependent manner, SAAP-148 and halicin reduced bacterial counts in 24 h preformed biofilms on silicone elastomer discs and eliminated persisters originating from antibiotic-exposed mature 7-day biofilms, with halicin being less effective than SAAP-148. Importantly, SAAP-148 and halicin acted synergistically on <i<E. coli</i< and <i<K. pneumoniae</i< biofilms but not on <i<A. baumannii</i< biofilms. The peptide, but not halicin, decreased the production of IL-12p40 upon exposure to UV-killed bacteria. This preliminary study showed that SAAP-148 and halicin alone/in combination are promising candidates to fight GNB colonizing catheters. |
abstract_unstemmed |
The antibiotic management of catheter-related infections (CRIs) often fails owing to the emergence of antimicrobial-resistant strains and/or biofilm/persister apparitions. Thus, we investigated the efficacy of two novel antimicrobial agents, i.e., the synthetic peptide SAAP-148 and the novel antibiotic halicin, against Gram-negative bacteria (GNB) colonizing catheters. The antibacterial, anti-biofilm, and anti-persister activities of both agents were evaluated against <i<Acinetobacter baumannii</i<, <i<Escherichia coli</i<, and <i<Klebsiella pneumoniae</i< strains. The enrolled strains were isolated from catheters and selected based on their resistance to at least three antibiotic classes and biofilm formation potential. Furthermore, the hemolysis and endotoxin neutralization abilities of these agents were explored. The bactericidal activity of both agents was reduced in urine and plasma as compared to buffered saline. In a dose-dependent manner, SAAP-148 and halicin reduced bacterial counts in 24 h preformed biofilms on silicone elastomer discs and eliminated persisters originating from antibiotic-exposed mature 7-day biofilms, with halicin being less effective than SAAP-148. Importantly, SAAP-148 and halicin acted synergistically on <i<E. coli</i< and <i<K. pneumoniae</i< biofilms but not on <i<A. baumannii</i< biofilms. The peptide, but not halicin, decreased the production of IL-12p40 upon exposure to UV-killed bacteria. This preliminary study showed that SAAP-148 and halicin alone/in combination are promising candidates to fight GNB colonizing catheters. |
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Thus, we investigated the efficacy of two novel antimicrobial agents, i.e., the synthetic peptide SAAP-148 and the novel antibiotic halicin, against Gram-negative bacteria (GNB) colonizing catheters. The antibacterial, anti-biofilm, and anti-persister activities of both agents were evaluated against <i<Acinetobacter baumannii</i<, <i<Escherichia coli</i<, and <i<Klebsiella pneumoniae</i< strains. The enrolled strains were isolated from catheters and selected based on their resistance to at least three antibiotic classes and biofilm formation potential. Furthermore, the hemolysis and endotoxin neutralization abilities of these agents were explored. The bactericidal activity of both agents was reduced in urine and plasma as compared to buffered saline. In a dose-dependent manner, SAAP-148 and halicin reduced bacterial counts in 24 h preformed biofilms on silicone elastomer discs and eliminated persisters originating from antibiotic-exposed mature 7-day biofilms, with halicin being less effective than SAAP-148. Importantly, SAAP-148 and halicin acted synergistically on <i<E. coli</i< and <i<K. pneumoniae</i< biofilms but not on <i<A. baumannii</i< biofilms. The peptide, but not halicin, decreased the production of IL-12p40 upon exposure to UV-killed bacteria. This preliminary study showed that SAAP-148 and halicin alone/in combination are promising candidates to fight GNB colonizing catheters.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">catheter</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">antibiotic resistance</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">biofilm</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">persisters</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">halicin</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">SAAP-148</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Therapeutics. Pharmacology</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Tanny J. 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