Abstract:
:Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that poses a significant risk to global health today. We have developed a promising new FtsZ-targeting agent (TXA707) with potent activity against MRSA isolates resistant to current standard-of-care antibiotics. We present here results that demonstrate differing extents of synergy between TXA707 and a broad range of β-lactam antibiotics (including six cephalosporins, two penicillins, and two carbapenems) against MRSA. To explore whether there is a correlation between the extent of synergy and the preferential antibacterial target of each β-lactam, we determined the binding affinities of the β-lactam antibiotics for each of the four native penicillin-binding proteins (PBPs) of S. aureus using a fluorescence anisotropy competition assay. A comparison of the resulting PBP binding affinities with our corresponding synergy results reveals that β-lactams with a high affinity for PBP2 afford the greatest degree of synergy with TXA707 against MRSA. In addition, we present fluorescence and electron microscopy studies that suggest a potential mechanism underlying the synergy between TXA707 and the β-lactam antibiotics. In this connection, our microscopy results show a disruption of septum formation in TXA707-treated MRSA cells, with a concomitant mislocalization of the PBPs from midcell to nonproductive peripheral sites. Viewed as a whole, our results indicate that PBP2-targeting β-lactam antibiotics are optimal synergistic partners with FtsZ-targeting agents for use in combination therapy of MRSA infections.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Ferrer-González E,Kaul M,Parhi AK,LaVoie EJ,Pilch DSdoi
10.1128/AAC.00863-17subject
Has Abstractpub_date
2017-08-24 00:00:00issue
9eissn
0066-4804issn
1098-6596pii
AAC.00863-17journal_volume
61pub_type
杂志文章abstract::The efficacy of an itraconazole-cyclodextrin solution against Aspergillus fumigatus was assessed in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis and compared with that of amphotericin B. Oral itraconazole solution at dosages of 20 and 40 mg/kg/day improved survival as compared wit...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.11.2307
更新日期:1993-11-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01421-16
更新日期:2016-11-21 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.9.2111
更新日期:1996-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/aac.46.10.3280-3282.2002
更新日期:2002-10-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.12.3644-3646.2001
更新日期:2001-12-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.5.770
更新日期:1984-11-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.1.398-405.2005
更新日期:2005-01-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.00277-10
更新日期:2012-01-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.3.399
更新日期:1978-03-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00979-18
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01285-07
更新日期:2008-04-01 00:00:00
abstract::7-[alpha-(1-Methyl-4-pyridiniothio)-acetamido] cephalosporanic acid, referred to herein as BL-S 217, is a new broad-spectrum semisynthetic cephalosporin that offers several advantages over cephalothin. A comparison of the activity in vitro of these antibiotics indicates that BL-S 217 is about eightfold more effective ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.1.1.67
更新日期:1972-01-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00744-18
更新日期:2018-07-27 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00414-07
更新日期:2008-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02066-13
更新日期:2014-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00576-08
更新日期:2009-02-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00385-20
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:1995-02-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.8.1601
更新日期:1992-08-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.5.804
更新日期:1982-05-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.2.441-443.2000
更新日期:2000-02-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.2.240
更新日期:1985-08-01 00:00:00
abstract::Thirty-nine fosfomycin-resistant Escherichia coli isolates carrying fosA3 were obtained from pigs, chickens, dairy cows, and staff in four northeastern provinces of China between June 2015 and April 2016. The fosA3 gene was colocated with blaCTX-M genes on conjugative plasmids of the incompatibility groups IncN (n = 1...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00859-17
更新日期:2017-08-24 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2014-07-01 00:00:00
abstract::Imipenem-cilastatin concentrations in bile were measured in 12 cholecystectomy patients (group 1) and 12 patients with common duct drainage (group 2). Six patients in each group received 0.5 g, and six received 1.0 g intravenously over 30 to 60 min. In group 1, bile was collected a mean of 85 min postinfusion. The mea...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.11.1718
更新日期:1987-11-01 00:00:00