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Nordihydroguaiaretic acid enhances the activities of aminoglycosides against methicillin-sensitive and resistant Staphylococcus aureus in vitro and in vivo

Nordihydroguaiaretic acid enhances the activities of aminoglycosides against methicillin-sensitive and resistant Staphylococcus aureus in vitro and in vivo
Nordihydroguaiaretic acid enhances the activities of aminoglycosides against methicillin-sensitive and resistant Staphylococcus aureus in vitro and in vivo
Infections caused by methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) are prevalent. MRSA infections are difficult to treat and there are no new classes of antibiotics produced to the market to treat infections caused by the resistant bacteria. Therefore, using antibiotic enhancers to rescue existing classes of antibiotics is an attractive strategy. Nordihydroguaiaretic acid (NDGA) is an antioxidant compound found in extracts from plant Larrea Tridentata. It exhibits antimicrobial activity and may target bacterial cell membrane. Combination efficacies of NDGA with many classes of antibiotics were examined by chequerboard method against 200 clinical isolates of MRSA and MSSA. NDGA in combination with gentamicin, neomycin, and tobramycin was examined by time-kill assays. The synergistic combinations of NDGA and aminoglycosides were tested in vivo using a murine skin infection model. Calculations of the fractional inhibitory concentration index (FICI) showed that NDGA when combined with gentamicin, neomycin, or tobramycin displayed synergistic activities in more than 97% of MSSA and MRSA, respectively. Time kill analysis demonstrated that NDGA significantly augmented the activities of these aminoglycosides against MRSA and MSSA in vitro and in murine skin infection model. The enhanced activity of NDGA resides on its ability to damage bacterial cell membrane leading to accumulation of the antibiotics inside bacterial cells. We demonstrated that NDGA strongly revived the therapeutic potencies of aminoglycosides in vitro and in vivo. This combinational strategy could contribute major clinical implications to treat antibiotic resistant bacterial infections.
nordihydroguaiaretic acid, gentamicin, neomycin, tobramycin, staphylococcus aureus, antibiotic combination
1664-302X
1-8
Cunningham-Oakes, Edward
cdd06285-90e2-49b5-97b9-7e4fad4b8318
Soren, Odel
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Moussa, Caroline
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Rathor, Getika
fef36764-a85f-4386-adc0-668f127ceb6d
Liu, Yingjun
e9c4ef2c-afec-4e16-978b-a57d09bb09d9
Coates, Anthony
8da8cc51-fab0-401b-b860-ab6456589a29
Hu, Yanmin
1ec1b062-4c43-4e47-a4fa-caacc5b4bcaf
Cunningham-Oakes, Edward
cdd06285-90e2-49b5-97b9-7e4fad4b8318
Soren, Odel
fbec1ab5-90ed-4515-a164-b374b0930a26
Moussa, Caroline
0d6710c1-f687-41b9-9598-59d7065ae0d3
Rathor, Getika
fef36764-a85f-4386-adc0-668f127ceb6d
Liu, Yingjun
e9c4ef2c-afec-4e16-978b-a57d09bb09d9
Coates, Anthony
8da8cc51-fab0-401b-b860-ab6456589a29
Hu, Yanmin
1ec1b062-4c43-4e47-a4fa-caacc5b4bcaf

Cunningham-Oakes, Edward, Soren, Odel, Moussa, Caroline, Rathor, Getika, Liu, Yingjun, Coates, Anthony and Hu, Yanmin (2015) Nordihydroguaiaretic acid enhances the activities of aminoglycosides against methicillin-sensitive and resistant Staphylococcus aureus in vitro and in vivo. Frontiers in Microbiology, 6, 1-8. (doi:10.3389/fmicb.2015.01195). (PMID:26579101)

Record type: Article

Abstract

Infections caused by methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) are prevalent. MRSA infections are difficult to treat and there are no new classes of antibiotics produced to the market to treat infections caused by the resistant bacteria. Therefore, using antibiotic enhancers to rescue existing classes of antibiotics is an attractive strategy. Nordihydroguaiaretic acid (NDGA) is an antioxidant compound found in extracts from plant Larrea Tridentata. It exhibits antimicrobial activity and may target bacterial cell membrane. Combination efficacies of NDGA with many classes of antibiotics were examined by chequerboard method against 200 clinical isolates of MRSA and MSSA. NDGA in combination with gentamicin, neomycin, and tobramycin was examined by time-kill assays. The synergistic combinations of NDGA and aminoglycosides were tested in vivo using a murine skin infection model. Calculations of the fractional inhibitory concentration index (FICI) showed that NDGA when combined with gentamicin, neomycin, or tobramycin displayed synergistic activities in more than 97% of MSSA and MRSA, respectively. Time kill analysis demonstrated that NDGA significantly augmented the activities of these aminoglycosides against MRSA and MSSA in vitro and in murine skin infection model. The enhanced activity of NDGA resides on its ability to damage bacterial cell membrane leading to accumulation of the antibiotics inside bacterial cells. We demonstrated that NDGA strongly revived the therapeutic potencies of aminoglycosides in vitro and in vivo. This combinational strategy could contribute major clinical implications to treat antibiotic resistant bacterial infections.

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Accepted/In Press date: 14 October 2015
Published date: 27 October 2015
Keywords: nordihydroguaiaretic acid, gentamicin, neomycin, tobramycin, staphylococcus aureus, antibiotic combination
Organisations: Biomedicine

Identifiers

Local EPrints ID: 388553
URI: https://eprints.soton.ac.uk/id/eprint/388553
ISSN: 1664-302X
PURE UUID: 509cc078-65fa-4597-9eeb-377210c06a73

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Date deposited: 29 Feb 2016 14:21
Last modified: 19 Jul 2019 20:16

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