Quinoxaline-based membrane-targeting therapeutic material: Implications in rejuvenating antibiotic and curb MRSA invasion in an

Manifestation of resistance in methicillin-resistant Staphylococcus aureus (MRSA) against multiple antibiotics demands an effective strategy to counter the menace of the pathogen. To address this challenge, the current study explores quinoxaline-based synthetic ligands as an adjuvant material to tar...
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Gespeichert in:

Autor*in:	Bhattacharjee, Basu [verfasserIn] Basak, Megha [verfasserIn] Das, Gopal [verfasserIn] Ramesh, Aiyagari [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	MRSA Quinoxaline Combination therapy Ciprofloxacin Bone cell

Übergeordnetes Werk:	Enthalten in: Biomaterials advances - Amsterdam : Elsevier, 2022, 148
Übergeordnetes Werk:	volume:148

DOI / URN:	10.1016/j.bioadv.2023.213359

Katalog-ID:	ELV009485201

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520			\|a Manifestation of resistance in methicillin-resistant Staphylococcus aureus (MRSA) against multiple antibiotics demands an effective strategy to counter the menace of the pathogen. To address this challenge, the current study explores quinoxaline-based synthetic ligands as an adjuvant material to target MRSA in a combination therapy regimen. Amongst the tested ligands (C1-C4), only C2 was bactericidal against the MRSA strain S. aureus 4 s, with a minimum inhibitory concentration (MIC) of 32 μM. C2 displayed a membrane-directed activity and could effectively hinder MRSA biofilm formation. A quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that C2 downregulated expression of the regulator gene agrC and reduced the fold change in the expression of adhesin genes fnbA and cnbA in MRSA in a dose-dependent manner. C2 enabled a 4-fold reduction in the MIC of ciprofloxacin (CPX) and in presence of 10 μM C2 and 8.0 μM CPX, growth of MRSA was arrested. Furthermore, a combination of 10 μM C2 and 12 μM CPX could strongly inhibit MRSA biofilm formation and reduce biofilm metabolic activity. The minimum biofilm inhibitory concentration (MBIC) of CPX against S. aureus 4 s biofilm was reduced and a synergy resulted between C2 and CPX. In a combinatorial treatment regimen, C2 could prevent emergence of CPX resistance and arrest growth of MRSA till 360 generations. C2 could also be leveraged in combination treatment (12 μM CPX and 10 μM C2) to target MRSA in an in vitro bone cell infection model, wherein MRSA cell adhesion and invasion onto cultured MG-63 cells was only ~17 % and ~ 0.37 %, respectively. The combinatorial treatment regimen was also biocompatible as the viability of MG-63 cells was high (~ 91 %). Thus, C2 is a promising adjuvant material to counter antibiotic-refractory therapy and mitigate MRSA-mediated bone cell infection.
650		4	\|a MRSA
650		4	\|a Quinoxaline
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912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
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912			\|a GBV_ILN_2020
912			\|a GBV_ILN_2021
912			\|a GBV_ILN_2025
912			\|a GBV_ILN_2026
912			\|a GBV_ILN_2027
912			\|a GBV_ILN_2034
912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
912			\|a GBV_ILN_2049
912			\|a GBV_ILN_2050
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2056
912			\|a GBV_ILN_2059
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912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4326
912			\|a GBV_ILN_4333
912			\|a GBV_ILN_4334
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4393
912			\|a GBV_ILN_4700
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publishDate	2023
allfields	10.1016/j.bioadv.2023.213359 doi (DE-627)ELV009485201 (ELSEVIER)S2772-9508(23)00082-1 DE-627 ger DE-627 rda eng 570 600 DE-600 Bhattacharjee, Basu verfasserin aut Quinoxaline-based membrane-targeting therapeutic material: Implications in rejuvenating antibiotic and curb MRSA invasion in an 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Manifestation of resistance in methicillin-resistant Staphylococcus aureus (MRSA) against multiple antibiotics demands an effective strategy to counter the menace of the pathogen. To address this challenge, the current study explores quinoxaline-based synthetic ligands as an adjuvant material to target MRSA in a combination therapy regimen. Amongst the tested ligands (C1-C4), only C2 was bactericidal against the MRSA strain S. aureus 4 s, with a minimum inhibitory concentration (MIC) of 32 μM. C2 displayed a membrane-directed activity and could effectively hinder MRSA biofilm formation. A quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that C2 downregulated expression of the regulator gene agrC and reduced the fold change in the expression of adhesin genes fnbA and cnbA in MRSA in a dose-dependent manner. C2 enabled a 4-fold reduction in the MIC of ciprofloxacin (CPX) and in presence of 10 μM C2 and 8.0 μM CPX, growth of MRSA was arrested. Furthermore, a combination of 10 μM C2 and 12 μM CPX could strongly inhibit MRSA biofilm formation and reduce biofilm metabolic activity. The minimum biofilm inhibitory concentration (MBIC) of CPX against S. aureus 4 s biofilm was reduced and a synergy resulted between C2 and CPX. In a combinatorial treatment regimen, C2 could prevent emergence of CPX resistance and arrest growth of MRSA till 360 generations. C2 could also be leveraged in combination treatment (12 μM CPX and 10 μM C2) to target MRSA in an in vitro bone cell infection model, wherein MRSA cell adhesion and invasion onto cultured MG-63 cells was only ~17 % and ~ 0.37 %, respectively. The combinatorial treatment regimen was also biocompatible as the viability of MG-63 cells was high (~ 91 %). Thus, C2 is a promising adjuvant material to counter antibiotic-refractory therapy and mitigate MRSA-mediated bone cell infection. MRSA Quinoxaline Combination therapy Ciprofloxacin Bone cell Basak, Megha verfasserin aut Das, Gopal verfasserin aut Ramesh, Aiyagari verfasserin aut Enthalten in Biomaterials advances Amsterdam : Elsevier, 2022 148 Online-Ressource (DE-627)1819876942 (DE-600)3138219-8 2772-9508 nnns volume:148 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 148
spelling	10.1016/j.bioadv.2023.213359 doi (DE-627)ELV009485201 (ELSEVIER)S2772-9508(23)00082-1 DE-627 ger DE-627 rda eng 570 600 DE-600 Bhattacharjee, Basu verfasserin aut Quinoxaline-based membrane-targeting therapeutic material: Implications in rejuvenating antibiotic and curb MRSA invasion in an 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Manifestation of resistance in methicillin-resistant Staphylococcus aureus (MRSA) against multiple antibiotics demands an effective strategy to counter the menace of the pathogen. To address this challenge, the current study explores quinoxaline-based synthetic ligands as an adjuvant material to target MRSA in a combination therapy regimen. Amongst the tested ligands (C1-C4), only C2 was bactericidal against the MRSA strain S. aureus 4 s, with a minimum inhibitory concentration (MIC) of 32 μM. C2 displayed a membrane-directed activity and could effectively hinder MRSA biofilm formation. A quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that C2 downregulated expression of the regulator gene agrC and reduced the fold change in the expression of adhesin genes fnbA and cnbA in MRSA in a dose-dependent manner. C2 enabled a 4-fold reduction in the MIC of ciprofloxacin (CPX) and in presence of 10 μM C2 and 8.0 μM CPX, growth of MRSA was arrested. Furthermore, a combination of 10 μM C2 and 12 μM CPX could strongly inhibit MRSA biofilm formation and reduce biofilm metabolic activity. The minimum biofilm inhibitory concentration (MBIC) of CPX against S. aureus 4 s biofilm was reduced and a synergy resulted between C2 and CPX. In a combinatorial treatment regimen, C2 could prevent emergence of CPX resistance and arrest growth of MRSA till 360 generations. C2 could also be leveraged in combination treatment (12 μM CPX and 10 μM C2) to target MRSA in an in vitro bone cell infection model, wherein MRSA cell adhesion and invasion onto cultured MG-63 cells was only ~17 % and ~ 0.37 %, respectively. The combinatorial treatment regimen was also biocompatible as the viability of MG-63 cells was high (~ 91 %). Thus, C2 is a promising adjuvant material to counter antibiotic-refractory therapy and mitigate MRSA-mediated bone cell infection. MRSA Quinoxaline Combination therapy Ciprofloxacin Bone cell Basak, Megha verfasserin aut Das, Gopal verfasserin aut Ramesh, Aiyagari verfasserin aut Enthalten in Biomaterials advances Amsterdam : Elsevier, 2022 148 Online-Ressource (DE-627)1819876942 (DE-600)3138219-8 2772-9508 nnns volume:148 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 148
allfields_unstemmed	10.1016/j.bioadv.2023.213359 doi (DE-627)ELV009485201 (ELSEVIER)S2772-9508(23)00082-1 DE-627 ger DE-627 rda eng 570 600 DE-600 Bhattacharjee, Basu verfasserin aut Quinoxaline-based membrane-targeting therapeutic material: Implications in rejuvenating antibiotic and curb MRSA invasion in an 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Manifestation of resistance in methicillin-resistant Staphylococcus aureus (MRSA) against multiple antibiotics demands an effective strategy to counter the menace of the pathogen. To address this challenge, the current study explores quinoxaline-based synthetic ligands as an adjuvant material to target MRSA in a combination therapy regimen. Amongst the tested ligands (C1-C4), only C2 was bactericidal against the MRSA strain S. aureus 4 s, with a minimum inhibitory concentration (MIC) of 32 μM. C2 displayed a membrane-directed activity and could effectively hinder MRSA biofilm formation. A quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that C2 downregulated expression of the regulator gene agrC and reduced the fold change in the expression of adhesin genes fnbA and cnbA in MRSA in a dose-dependent manner. C2 enabled a 4-fold reduction in the MIC of ciprofloxacin (CPX) and in presence of 10 μM C2 and 8.0 μM CPX, growth of MRSA was arrested. Furthermore, a combination of 10 μM C2 and 12 μM CPX could strongly inhibit MRSA biofilm formation and reduce biofilm metabolic activity. The minimum biofilm inhibitory concentration (MBIC) of CPX against S. aureus 4 s biofilm was reduced and a synergy resulted between C2 and CPX. In a combinatorial treatment regimen, C2 could prevent emergence of CPX resistance and arrest growth of MRSA till 360 generations. C2 could also be leveraged in combination treatment (12 μM CPX and 10 μM C2) to target MRSA in an in vitro bone cell infection model, wherein MRSA cell adhesion and invasion onto cultured MG-63 cells was only ~17 % and ~ 0.37 %, respectively. The combinatorial treatment regimen was also biocompatible as the viability of MG-63 cells was high (~ 91 %). Thus, C2 is a promising adjuvant material to counter antibiotic-refractory therapy and mitigate MRSA-mediated bone cell infection. MRSA Quinoxaline Combination therapy Ciprofloxacin Bone cell Basak, Megha verfasserin aut Das, Gopal verfasserin aut Ramesh, Aiyagari verfasserin aut Enthalten in Biomaterials advances Amsterdam : Elsevier, 2022 148 Online-Ressource (DE-627)1819876942 (DE-600)3138219-8 2772-9508 nnns volume:148 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 148
allfieldsGer	10.1016/j.bioadv.2023.213359 doi (DE-627)ELV009485201 (ELSEVIER)S2772-9508(23)00082-1 DE-627 ger DE-627 rda eng 570 600 DE-600 Bhattacharjee, Basu verfasserin aut Quinoxaline-based membrane-targeting therapeutic material: Implications in rejuvenating antibiotic and curb MRSA invasion in an 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Manifestation of resistance in methicillin-resistant Staphylococcus aureus (MRSA) against multiple antibiotics demands an effective strategy to counter the menace of the pathogen. To address this challenge, the current study explores quinoxaline-based synthetic ligands as an adjuvant material to target MRSA in a combination therapy regimen. Amongst the tested ligands (C1-C4), only C2 was bactericidal against the MRSA strain S. aureus 4 s, with a minimum inhibitory concentration (MIC) of 32 μM. C2 displayed a membrane-directed activity and could effectively hinder MRSA biofilm formation. A quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that C2 downregulated expression of the regulator gene agrC and reduced the fold change in the expression of adhesin genes fnbA and cnbA in MRSA in a dose-dependent manner. C2 enabled a 4-fold reduction in the MIC of ciprofloxacin (CPX) and in presence of 10 μM C2 and 8.0 μM CPX, growth of MRSA was arrested. Furthermore, a combination of 10 μM C2 and 12 μM CPX could strongly inhibit MRSA biofilm formation and reduce biofilm metabolic activity. The minimum biofilm inhibitory concentration (MBIC) of CPX against S. aureus 4 s biofilm was reduced and a synergy resulted between C2 and CPX. In a combinatorial treatment regimen, C2 could prevent emergence of CPX resistance and arrest growth of MRSA till 360 generations. C2 could also be leveraged in combination treatment (12 μM CPX and 10 μM C2) to target MRSA in an in vitro bone cell infection model, wherein MRSA cell adhesion and invasion onto cultured MG-63 cells was only ~17 % and ~ 0.37 %, respectively. The combinatorial treatment regimen was also biocompatible as the viability of MG-63 cells was high (~ 91 %). Thus, C2 is a promising adjuvant material to counter antibiotic-refractory therapy and mitigate MRSA-mediated bone cell infection. MRSA Quinoxaline Combination therapy Ciprofloxacin Bone cell Basak, Megha verfasserin aut Das, Gopal verfasserin aut Ramesh, Aiyagari verfasserin aut Enthalten in Biomaterials advances Amsterdam : Elsevier, 2022 148 Online-Ressource (DE-627)1819876942 (DE-600)3138219-8 2772-9508 nnns volume:148 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 148
allfieldsSound	10.1016/j.bioadv.2023.213359 doi (DE-627)ELV009485201 (ELSEVIER)S2772-9508(23)00082-1 DE-627 ger DE-627 rda eng 570 600 DE-600 Bhattacharjee, Basu verfasserin aut Quinoxaline-based membrane-targeting therapeutic material: Implications in rejuvenating antibiotic and curb MRSA invasion in an 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Manifestation of resistance in methicillin-resistant Staphylococcus aureus (MRSA) against multiple antibiotics demands an effective strategy to counter the menace of the pathogen. To address this challenge, the current study explores quinoxaline-based synthetic ligands as an adjuvant material to target MRSA in a combination therapy regimen. Amongst the tested ligands (C1-C4), only C2 was bactericidal against the MRSA strain S. aureus 4 s, with a minimum inhibitory concentration (MIC) of 32 μM. C2 displayed a membrane-directed activity and could effectively hinder MRSA biofilm formation. A quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that C2 downregulated expression of the regulator gene agrC and reduced the fold change in the expression of adhesin genes fnbA and cnbA in MRSA in a dose-dependent manner. C2 enabled a 4-fold reduction in the MIC of ciprofloxacin (CPX) and in presence of 10 μM C2 and 8.0 μM CPX, growth of MRSA was arrested. Furthermore, a combination of 10 μM C2 and 12 μM CPX could strongly inhibit MRSA biofilm formation and reduce biofilm metabolic activity. The minimum biofilm inhibitory concentration (MBIC) of CPX against S. aureus 4 s biofilm was reduced and a synergy resulted between C2 and CPX. In a combinatorial treatment regimen, C2 could prevent emergence of CPX resistance and arrest growth of MRSA till 360 generations. C2 could also be leveraged in combination treatment (12 μM CPX and 10 μM C2) to target MRSA in an in vitro bone cell infection model, wherein MRSA cell adhesion and invasion onto cultured MG-63 cells was only ~17 % and ~ 0.37 %, respectively. The combinatorial treatment regimen was also biocompatible as the viability of MG-63 cells was high (~ 91 %). Thus, C2 is a promising adjuvant material to counter antibiotic-refractory therapy and mitigate MRSA-mediated bone cell infection. MRSA Quinoxaline Combination therapy Ciprofloxacin Bone cell Basak, Megha verfasserin aut Das, Gopal verfasserin aut Ramesh, Aiyagari verfasserin aut Enthalten in Biomaterials advances Amsterdam : Elsevier, 2022 148 Online-Ressource (DE-627)1819876942 (DE-600)3138219-8 2772-9508 nnns volume:148 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 148
language	English
source	Enthalten in Biomaterials advances 148 volume:148
sourceStr	Enthalten in Biomaterials advances 148 volume:148
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	MRSA Quinoxaline Combination therapy Ciprofloxacin Bone cell
dewey-raw	570
isfreeaccess_bool	false
container_title	Biomaterials advances
authorswithroles_txt_mv	Bhattacharjee, Basu @@aut@@ Basak, Megha @@aut@@ Das, Gopal @@aut@@ Ramesh, Aiyagari @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	1819876942
dewey-sort	3570
id	ELV009485201
language_de	englisch
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author	Bhattacharjee, Basu
spellingShingle	Bhattacharjee, Basu ddc 570 misc MRSA misc Quinoxaline misc Combination therapy misc Ciprofloxacin misc Bone cell Quinoxaline-based membrane-targeting therapeutic material: Implications in rejuvenating antibiotic and curb MRSA invasion in an
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topic_title	570 600 DE-600 Quinoxaline-based membrane-targeting therapeutic material: Implications in rejuvenating antibiotic and curb MRSA invasion in an MRSA Quinoxaline Combination therapy Ciprofloxacin Bone cell
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title	Quinoxaline-based membrane-targeting therapeutic material: Implications in rejuvenating antibiotic and curb MRSA invasion in an
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title_full	Quinoxaline-based membrane-targeting therapeutic material: Implications in rejuvenating antibiotic and curb MRSA invasion in an
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title_sort	quinoxaline-based membrane-targeting therapeutic material: implications in rejuvenating antibiotic and curb mrsa invasion in an
title_auth	Quinoxaline-based membrane-targeting therapeutic material: Implications in rejuvenating antibiotic and curb MRSA invasion in an
abstract	Manifestation of resistance in methicillin-resistant Staphylococcus aureus (MRSA) against multiple antibiotics demands an effective strategy to counter the menace of the pathogen. To address this challenge, the current study explores quinoxaline-based synthetic ligands as an adjuvant material to target MRSA in a combination therapy regimen. Amongst the tested ligands (C1-C4), only C2 was bactericidal against the MRSA strain S. aureus 4 s, with a minimum inhibitory concentration (MIC) of 32 μM. C2 displayed a membrane-directed activity and could effectively hinder MRSA biofilm formation. A quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that C2 downregulated expression of the regulator gene agrC and reduced the fold change in the expression of adhesin genes fnbA and cnbA in MRSA in a dose-dependent manner. C2 enabled a 4-fold reduction in the MIC of ciprofloxacin (CPX) and in presence of 10 μM C2 and 8.0 μM CPX, growth of MRSA was arrested. Furthermore, a combination of 10 μM C2 and 12 μM CPX could strongly inhibit MRSA biofilm formation and reduce biofilm metabolic activity. The minimum biofilm inhibitory concentration (MBIC) of CPX against S. aureus 4 s biofilm was reduced and a synergy resulted between C2 and CPX. In a combinatorial treatment regimen, C2 could prevent emergence of CPX resistance and arrest growth of MRSA till 360 generations. C2 could also be leveraged in combination treatment (12 μM CPX and 10 μM C2) to target MRSA in an in vitro bone cell infection model, wherein MRSA cell adhesion and invasion onto cultured MG-63 cells was only ~17 % and ~ 0.37 %, respectively. The combinatorial treatment regimen was also biocompatible as the viability of MG-63 cells was high (~ 91 %). Thus, C2 is a promising adjuvant material to counter antibiotic-refractory therapy and mitigate MRSA-mediated bone cell infection.
abstractGer	Manifestation of resistance in methicillin-resistant Staphylococcus aureus (MRSA) against multiple antibiotics demands an effective strategy to counter the menace of the pathogen. To address this challenge, the current study explores quinoxaline-based synthetic ligands as an adjuvant material to target MRSA in a combination therapy regimen. Amongst the tested ligands (C1-C4), only C2 was bactericidal against the MRSA strain S. aureus 4 s, with a minimum inhibitory concentration (MIC) of 32 μM. C2 displayed a membrane-directed activity and could effectively hinder MRSA biofilm formation. A quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that C2 downregulated expression of the regulator gene agrC and reduced the fold change in the expression of adhesin genes fnbA and cnbA in MRSA in a dose-dependent manner. C2 enabled a 4-fold reduction in the MIC of ciprofloxacin (CPX) and in presence of 10 μM C2 and 8.0 μM CPX, growth of MRSA was arrested. Furthermore, a combination of 10 μM C2 and 12 μM CPX could strongly inhibit MRSA biofilm formation and reduce biofilm metabolic activity. The minimum biofilm inhibitory concentration (MBIC) of CPX against S. aureus 4 s biofilm was reduced and a synergy resulted between C2 and CPX. In a combinatorial treatment regimen, C2 could prevent emergence of CPX resistance and arrest growth of MRSA till 360 generations. C2 could also be leveraged in combination treatment (12 μM CPX and 10 μM C2) to target MRSA in an in vitro bone cell infection model, wherein MRSA cell adhesion and invasion onto cultured MG-63 cells was only ~17 % and ~ 0.37 %, respectively. The combinatorial treatment regimen was also biocompatible as the viability of MG-63 cells was high (~ 91 %). Thus, C2 is a promising adjuvant material to counter antibiotic-refractory therapy and mitigate MRSA-mediated bone cell infection.
abstract_unstemmed	Manifestation of resistance in methicillin-resistant Staphylococcus aureus (MRSA) against multiple antibiotics demands an effective strategy to counter the menace of the pathogen. To address this challenge, the current study explores quinoxaline-based synthetic ligands as an adjuvant material to target MRSA in a combination therapy regimen. Amongst the tested ligands (C1-C4), only C2 was bactericidal against the MRSA strain S. aureus 4 s, with a minimum inhibitory concentration (MIC) of 32 μM. C2 displayed a membrane-directed activity and could effectively hinder MRSA biofilm formation. A quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that C2 downregulated expression of the regulator gene agrC and reduced the fold change in the expression of adhesin genes fnbA and cnbA in MRSA in a dose-dependent manner. C2 enabled a 4-fold reduction in the MIC of ciprofloxacin (CPX) and in presence of 10 μM C2 and 8.0 μM CPX, growth of MRSA was arrested. Furthermore, a combination of 10 μM C2 and 12 μM CPX could strongly inhibit MRSA biofilm formation and reduce biofilm metabolic activity. The minimum biofilm inhibitory concentration (MBIC) of CPX against S. aureus 4 s biofilm was reduced and a synergy resulted between C2 and CPX. In a combinatorial treatment regimen, C2 could prevent emergence of CPX resistance and arrest growth of MRSA till 360 generations. C2 could also be leveraged in combination treatment (12 μM CPX and 10 μM C2) to target MRSA in an in vitro bone cell infection model, wherein MRSA cell adhesion and invasion onto cultured MG-63 cells was only ~17 % and ~ 0.37 %, respectively. The combinatorial treatment regimen was also biocompatible as the viability of MG-63 cells was high (~ 91 %). Thus, C2 is a promising adjuvant material to counter antibiotic-refractory therapy and mitigate MRSA-mediated bone cell infection.
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title_short	Quinoxaline-based membrane-targeting therapeutic material: Implications in rejuvenating antibiotic and curb MRSA invasion in an
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