Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella

It has been recognized that colistin resistance is a growing problem that seriously impairs the clinical efficacy of colistin against bacterial infections. One strategy that has been proven to have therapeutic effect is to overcome the widespread emergence of antibiotic-resistant pathogens by combin...
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Autor*in:	Kaifang Yi [verfasserIn] Shuobo Liu [verfasserIn] Peiyi Liu [verfasserIn] Xingwei Luo [verfasserIn] Jinfeng Zhao [verfasserIn] Fengbin Yan [verfasserIn] Yushan Pan [verfasserIn] Jianhua Liu [verfasserIn] Yajun Zhai [verfasserIn] Gongzheng Hu [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Antibiotic adjuvant Colistin Tetrandrine MCR-1 inhibitor Salmonella

Übergeordnetes Werk:	In: Biomedicine & Pharmacotherapy - Elsevier, 2021, 149(2022), Seite 112873-
Übergeordnetes Werk:	volume:149 ; year:2022 ; pages:112873-

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.biopha.2022.112873

Katalog-ID:	DOAJ040877302

Internformat


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520			\|a It has been recognized that colistin resistance is a growing problem that seriously impairs the clinical efficacy of colistin against bacterial infections. One strategy that has been proven to have therapeutic effect is to overcome the widespread emergence of antibiotic-resistant pathogens by combining existing antibiotics with promising non-antibiotic agents. In this work, antibiotic susceptibility testing, checkerboard assays and time-kill curves were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of the combination. The molecular mechanisms of tetrandrine in combination with colistin were analyzed using fluorometric assay and Real-time PCR. To predict possible interactions between tetrandrine and MCR-1, molecular docking assay was taken. Finally, we evaluated the in vivo efficacy of tetrandrine in combination with colistin against MCR-positive Salmonella. Overall, the combination of tetrandrine and colistin showed significant synergistic activity. In-depth mechanistic analysis showed that the combination of tetrandrine with colistin enhances the membrane-damaging ability of colistin, undermines the functions of proton motive force (PMF) and efflux pumps in MCR-positive bacteria. The results of molecular docking and RT-PCR analyses showed that tetrandrine not only affects the expression of mcr-1 but is also an effective MCR-1 inhibitor. Compared with colistin monotherapy, the combination of tetrandrine with colistin significantly reduced the bacterial load in vivo. Our findings demonstrated that tetrandrine serves as a potential colistin adjuvant against MCR-positive Salmonella.
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allfields	10.1016/j.biopha.2022.112873 doi (DE-627)DOAJ040877302 (DE-599)DOAJ430dff8dd5044998bc700a229f7febde DE-627 ger DE-627 rakwb eng RM1-950 Kaifang Yi verfasserin aut Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier It has been recognized that colistin resistance is a growing problem that seriously impairs the clinical efficacy of colistin against bacterial infections. One strategy that has been proven to have therapeutic effect is to overcome the widespread emergence of antibiotic-resistant pathogens by combining existing antibiotics with promising non-antibiotic agents. In this work, antibiotic susceptibility testing, checkerboard assays and time-kill curves were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of the combination. The molecular mechanisms of tetrandrine in combination with colistin were analyzed using fluorometric assay and Real-time PCR. To predict possible interactions between tetrandrine and MCR-1, molecular docking assay was taken. Finally, we evaluated the in vivo efficacy of tetrandrine in combination with colistin against MCR-positive Salmonella. Overall, the combination of tetrandrine and colistin showed significant synergistic activity. In-depth mechanistic analysis showed that the combination of tetrandrine with colistin enhances the membrane-damaging ability of colistin, undermines the functions of proton motive force (PMF) and efflux pumps in MCR-positive bacteria. The results of molecular docking and RT-PCR analyses showed that tetrandrine not only affects the expression of mcr-1 but is also an effective MCR-1 inhibitor. Compared with colistin monotherapy, the combination of tetrandrine with colistin significantly reduced the bacterial load in vivo. Our findings demonstrated that tetrandrine serves as a potential colistin adjuvant against MCR-positive Salmonella. Antibiotic adjuvant Colistin Tetrandrine MCR-1 inhibitor Salmonella Therapeutics. Pharmacology Shuobo Liu verfasserin aut Peiyi Liu verfasserin aut Xingwei Luo verfasserin aut Jinfeng Zhao verfasserin aut Fengbin Yan verfasserin aut Yushan Pan verfasserin aut Jianhua Liu verfasserin aut Yajun Zhai verfasserin aut Gongzheng Hu verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 149(2022), Seite 112873- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:149 year:2022 pages:112873- https://doi.org/10.1016/j.biopha.2022.112873 kostenfrei https://doaj.org/article/430dff8dd5044998bc700a229f7febde kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332222002621 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 149 2022 112873-
spelling	10.1016/j.biopha.2022.112873 doi (DE-627)DOAJ040877302 (DE-599)DOAJ430dff8dd5044998bc700a229f7febde DE-627 ger DE-627 rakwb eng RM1-950 Kaifang Yi verfasserin aut Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier It has been recognized that colistin resistance is a growing problem that seriously impairs the clinical efficacy of colistin against bacterial infections. One strategy that has been proven to have therapeutic effect is to overcome the widespread emergence of antibiotic-resistant pathogens by combining existing antibiotics with promising non-antibiotic agents. In this work, antibiotic susceptibility testing, checkerboard assays and time-kill curves were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of the combination. The molecular mechanisms of tetrandrine in combination with colistin were analyzed using fluorometric assay and Real-time PCR. To predict possible interactions between tetrandrine and MCR-1, molecular docking assay was taken. Finally, we evaluated the in vivo efficacy of tetrandrine in combination with colistin against MCR-positive Salmonella. Overall, the combination of tetrandrine and colistin showed significant synergistic activity. In-depth mechanistic analysis showed that the combination of tetrandrine with colistin enhances the membrane-damaging ability of colistin, undermines the functions of proton motive force (PMF) and efflux pumps in MCR-positive bacteria. The results of molecular docking and RT-PCR analyses showed that tetrandrine not only affects the expression of mcr-1 but is also an effective MCR-1 inhibitor. Compared with colistin monotherapy, the combination of tetrandrine with colistin significantly reduced the bacterial load in vivo. Our findings demonstrated that tetrandrine serves as a potential colistin adjuvant against MCR-positive Salmonella. Antibiotic adjuvant Colistin Tetrandrine MCR-1 inhibitor Salmonella Therapeutics. Pharmacology Shuobo Liu verfasserin aut Peiyi Liu verfasserin aut Xingwei Luo verfasserin aut Jinfeng Zhao verfasserin aut Fengbin Yan verfasserin aut Yushan Pan verfasserin aut Jianhua Liu verfasserin aut Yajun Zhai verfasserin aut Gongzheng Hu verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 149(2022), Seite 112873- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:149 year:2022 pages:112873- https://doi.org/10.1016/j.biopha.2022.112873 kostenfrei https://doaj.org/article/430dff8dd5044998bc700a229f7febde kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332222002621 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 149 2022 112873-
allfields_unstemmed	10.1016/j.biopha.2022.112873 doi (DE-627)DOAJ040877302 (DE-599)DOAJ430dff8dd5044998bc700a229f7febde DE-627 ger DE-627 rakwb eng RM1-950 Kaifang Yi verfasserin aut Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier It has been recognized that colistin resistance is a growing problem that seriously impairs the clinical efficacy of colistin against bacterial infections. One strategy that has been proven to have therapeutic effect is to overcome the widespread emergence of antibiotic-resistant pathogens by combining existing antibiotics with promising non-antibiotic agents. In this work, antibiotic susceptibility testing, checkerboard assays and time-kill curves were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of the combination. The molecular mechanisms of tetrandrine in combination with colistin were analyzed using fluorometric assay and Real-time PCR. To predict possible interactions between tetrandrine and MCR-1, molecular docking assay was taken. Finally, we evaluated the in vivo efficacy of tetrandrine in combination with colistin against MCR-positive Salmonella. Overall, the combination of tetrandrine and colistin showed significant synergistic activity. In-depth mechanistic analysis showed that the combination of tetrandrine with colistin enhances the membrane-damaging ability of colistin, undermines the functions of proton motive force (PMF) and efflux pumps in MCR-positive bacteria. The results of molecular docking and RT-PCR analyses showed that tetrandrine not only affects the expression of mcr-1 but is also an effective MCR-1 inhibitor. Compared with colistin monotherapy, the combination of tetrandrine with colistin significantly reduced the bacterial load in vivo. Our findings demonstrated that tetrandrine serves as a potential colistin adjuvant against MCR-positive Salmonella. Antibiotic adjuvant Colistin Tetrandrine MCR-1 inhibitor Salmonella Therapeutics. Pharmacology Shuobo Liu verfasserin aut Peiyi Liu verfasserin aut Xingwei Luo verfasserin aut Jinfeng Zhao verfasserin aut Fengbin Yan verfasserin aut Yushan Pan verfasserin aut Jianhua Liu verfasserin aut Yajun Zhai verfasserin aut Gongzheng Hu verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 149(2022), Seite 112873- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:149 year:2022 pages:112873- https://doi.org/10.1016/j.biopha.2022.112873 kostenfrei https://doaj.org/article/430dff8dd5044998bc700a229f7febde kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332222002621 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 149 2022 112873-
allfieldsGer	10.1016/j.biopha.2022.112873 doi (DE-627)DOAJ040877302 (DE-599)DOAJ430dff8dd5044998bc700a229f7febde DE-627 ger DE-627 rakwb eng RM1-950 Kaifang Yi verfasserin aut Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier It has been recognized that colistin resistance is a growing problem that seriously impairs the clinical efficacy of colistin against bacterial infections. One strategy that has been proven to have therapeutic effect is to overcome the widespread emergence of antibiotic-resistant pathogens by combining existing antibiotics with promising non-antibiotic agents. In this work, antibiotic susceptibility testing, checkerboard assays and time-kill curves were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of the combination. The molecular mechanisms of tetrandrine in combination with colistin were analyzed using fluorometric assay and Real-time PCR. To predict possible interactions between tetrandrine and MCR-1, molecular docking assay was taken. Finally, we evaluated the in vivo efficacy of tetrandrine in combination with colistin against MCR-positive Salmonella. Overall, the combination of tetrandrine and colistin showed significant synergistic activity. In-depth mechanistic analysis showed that the combination of tetrandrine with colistin enhances the membrane-damaging ability of colistin, undermines the functions of proton motive force (PMF) and efflux pumps in MCR-positive bacteria. The results of molecular docking and RT-PCR analyses showed that tetrandrine not only affects the expression of mcr-1 but is also an effective MCR-1 inhibitor. Compared with colistin monotherapy, the combination of tetrandrine with colistin significantly reduced the bacterial load in vivo. Our findings demonstrated that tetrandrine serves as a potential colistin adjuvant against MCR-positive Salmonella. Antibiotic adjuvant Colistin Tetrandrine MCR-1 inhibitor Salmonella Therapeutics. Pharmacology Shuobo Liu verfasserin aut Peiyi Liu verfasserin aut Xingwei Luo verfasserin aut Jinfeng Zhao verfasserin aut Fengbin Yan verfasserin aut Yushan Pan verfasserin aut Jianhua Liu verfasserin aut Yajun Zhai verfasserin aut Gongzheng Hu verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 149(2022), Seite 112873- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:149 year:2022 pages:112873- https://doi.org/10.1016/j.biopha.2022.112873 kostenfrei https://doaj.org/article/430dff8dd5044998bc700a229f7febde kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332222002621 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 149 2022 112873-
allfieldsSound	10.1016/j.biopha.2022.112873 doi (DE-627)DOAJ040877302 (DE-599)DOAJ430dff8dd5044998bc700a229f7febde DE-627 ger DE-627 rakwb eng RM1-950 Kaifang Yi verfasserin aut Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier It has been recognized that colistin resistance is a growing problem that seriously impairs the clinical efficacy of colistin against bacterial infections. One strategy that has been proven to have therapeutic effect is to overcome the widespread emergence of antibiotic-resistant pathogens by combining existing antibiotics with promising non-antibiotic agents. In this work, antibiotic susceptibility testing, checkerboard assays and time-kill curves were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of the combination. The molecular mechanisms of tetrandrine in combination with colistin were analyzed using fluorometric assay and Real-time PCR. To predict possible interactions between tetrandrine and MCR-1, molecular docking assay was taken. Finally, we evaluated the in vivo efficacy of tetrandrine in combination with colistin against MCR-positive Salmonella. Overall, the combination of tetrandrine and colistin showed significant synergistic activity. In-depth mechanistic analysis showed that the combination of tetrandrine with colistin enhances the membrane-damaging ability of colistin, undermines the functions of proton motive force (PMF) and efflux pumps in MCR-positive bacteria. The results of molecular docking and RT-PCR analyses showed that tetrandrine not only affects the expression of mcr-1 but is also an effective MCR-1 inhibitor. Compared with colistin monotherapy, the combination of tetrandrine with colistin significantly reduced the bacterial load in vivo. Our findings demonstrated that tetrandrine serves as a potential colistin adjuvant against MCR-positive Salmonella. Antibiotic adjuvant Colistin Tetrandrine MCR-1 inhibitor Salmonella Therapeutics. Pharmacology Shuobo Liu verfasserin aut Peiyi Liu verfasserin aut Xingwei Luo verfasserin aut Jinfeng Zhao verfasserin aut Fengbin Yan verfasserin aut Yushan Pan verfasserin aut Jianhua Liu verfasserin aut Yajun Zhai verfasserin aut Gongzheng Hu verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 149(2022), Seite 112873- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:149 year:2022 pages:112873- https://doi.org/10.1016/j.biopha.2022.112873 kostenfrei https://doaj.org/article/430dff8dd5044998bc700a229f7febde kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332222002621 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 149 2022 112873-
language	English
source	In Biomedicine & Pharmacotherapy 149(2022), Seite 112873- volume:149 year:2022 pages:112873-
sourceStr	In Biomedicine & Pharmacotherapy 149(2022), Seite 112873- volume:149 year:2022 pages:112873-
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Antibiotic adjuvant Colistin Tetrandrine MCR-1 inhibitor Salmonella Therapeutics. Pharmacology
isfreeaccess_bool	true
container_title	Biomedicine & Pharmacotherapy
authorswithroles_txt_mv	Kaifang Yi @@aut@@ Shuobo Liu @@aut@@ Peiyi Liu @@aut@@ Xingwei Luo @@aut@@ Jinfeng Zhao @@aut@@ Fengbin Yan @@aut@@ Yushan Pan @@aut@@ Jianhua Liu @@aut@@ Yajun Zhai @@aut@@ Gongzheng Hu @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	306717565
id	DOAJ040877302
language_de	englisch
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callnumber-first	R - Medicine
author	Kaifang Yi
spellingShingle	Kaifang Yi misc RM1-950 misc Antibiotic adjuvant misc Colistin misc Tetrandrine misc MCR-1 inhibitor misc Salmonella misc Therapeutics. Pharmacology Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella
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topic_title	RM1-950 Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella Antibiotic adjuvant Colistin Tetrandrine MCR-1 inhibitor Salmonella
topic	misc RM1-950 misc Antibiotic adjuvant misc Colistin misc Tetrandrine misc MCR-1 inhibitor misc Salmonella misc Therapeutics. Pharmacology
topic_unstemmed	misc RM1-950 misc Antibiotic adjuvant misc Colistin misc Tetrandrine misc MCR-1 inhibitor misc Salmonella misc Therapeutics. Pharmacology
topic_browse	misc RM1-950 misc Antibiotic adjuvant misc Colistin misc Tetrandrine misc MCR-1 inhibitor misc Salmonella misc Therapeutics. Pharmacology
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title	Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella
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title_full	Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella
author_sort	Kaifang Yi
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author_browse	Kaifang Yi Shuobo Liu Peiyi Liu Xingwei Luo Jinfeng Zhao Fengbin Yan Yushan Pan Jianhua Liu Yajun Zhai Gongzheng Hu
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title_sort	synergistic antibacterial activity of tetrandrine combined with colistin against mcr-mediated colistin-resistant salmonella
callnumber	RM1-950
title_auth	Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella
abstract	It has been recognized that colistin resistance is a growing problem that seriously impairs the clinical efficacy of colistin against bacterial infections. One strategy that has been proven to have therapeutic effect is to overcome the widespread emergence of antibiotic-resistant pathogens by combining existing antibiotics with promising non-antibiotic agents. In this work, antibiotic susceptibility testing, checkerboard assays and time-kill curves were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of the combination. The molecular mechanisms of tetrandrine in combination with colistin were analyzed using fluorometric assay and Real-time PCR. To predict possible interactions between tetrandrine and MCR-1, molecular docking assay was taken. Finally, we evaluated the in vivo efficacy of tetrandrine in combination with colistin against MCR-positive Salmonella. Overall, the combination of tetrandrine and colistin showed significant synergistic activity. In-depth mechanistic analysis showed that the combination of tetrandrine with colistin enhances the membrane-damaging ability of colistin, undermines the functions of proton motive force (PMF) and efflux pumps in MCR-positive bacteria. The results of molecular docking and RT-PCR analyses showed that tetrandrine not only affects the expression of mcr-1 but is also an effective MCR-1 inhibitor. Compared with colistin monotherapy, the combination of tetrandrine with colistin significantly reduced the bacterial load in vivo. Our findings demonstrated that tetrandrine serves as a potential colistin adjuvant against MCR-positive Salmonella.
abstractGer	It has been recognized that colistin resistance is a growing problem that seriously impairs the clinical efficacy of colistin against bacterial infections. One strategy that has been proven to have therapeutic effect is to overcome the widespread emergence of antibiotic-resistant pathogens by combining existing antibiotics with promising non-antibiotic agents. In this work, antibiotic susceptibility testing, checkerboard assays and time-kill curves were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of the combination. The molecular mechanisms of tetrandrine in combination with colistin were analyzed using fluorometric assay and Real-time PCR. To predict possible interactions between tetrandrine and MCR-1, molecular docking assay was taken. Finally, we evaluated the in vivo efficacy of tetrandrine in combination with colistin against MCR-positive Salmonella. Overall, the combination of tetrandrine and colistin showed significant synergistic activity. In-depth mechanistic analysis showed that the combination of tetrandrine with colistin enhances the membrane-damaging ability of colistin, undermines the functions of proton motive force (PMF) and efflux pumps in MCR-positive bacteria. The results of molecular docking and RT-PCR analyses showed that tetrandrine not only affects the expression of mcr-1 but is also an effective MCR-1 inhibitor. Compared with colistin monotherapy, the combination of tetrandrine with colistin significantly reduced the bacterial load in vivo. Our findings demonstrated that tetrandrine serves as a potential colistin adjuvant against MCR-positive Salmonella.
abstract_unstemmed	It has been recognized that colistin resistance is a growing problem that seriously impairs the clinical efficacy of colistin against bacterial infections. One strategy that has been proven to have therapeutic effect is to overcome the widespread emergence of antibiotic-resistant pathogens by combining existing antibiotics with promising non-antibiotic agents. In this work, antibiotic susceptibility testing, checkerboard assays and time-kill curves were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of the combination. The molecular mechanisms of tetrandrine in combination with colistin were analyzed using fluorometric assay and Real-time PCR. To predict possible interactions between tetrandrine and MCR-1, molecular docking assay was taken. Finally, we evaluated the in vivo efficacy of tetrandrine in combination with colistin against MCR-positive Salmonella. Overall, the combination of tetrandrine and colistin showed significant synergistic activity. In-depth mechanistic analysis showed that the combination of tetrandrine with colistin enhances the membrane-damaging ability of colistin, undermines the functions of proton motive force (PMF) and efflux pumps in MCR-positive bacteria. The results of molecular docking and RT-PCR analyses showed that tetrandrine not only affects the expression of mcr-1 but is also an effective MCR-1 inhibitor. Compared with colistin monotherapy, the combination of tetrandrine with colistin significantly reduced the bacterial load in vivo. Our findings demonstrated that tetrandrine serves as a potential colistin adjuvant against MCR-positive Salmonella.
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title_short	Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella
url	https://doi.org/10.1016/j.biopha.2022.112873 https://doaj.org/article/430dff8dd5044998bc700a229f7febde http://www.sciencedirect.com/science/article/pii/S0753332222002621 https://doaj.org/toc/0753-3322
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Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella

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