Dataset Information

Antibacterial and Antivirulence Activity of Manuka Honey against Genetically Diverse Staphylococcus pseudintermedius Strains.

ABSTRACT: Staphylococcus pseudintermedius causes opportunistic infections in dogs. It also has significant zoonotic potential, with the emergence of multidrug resistance leading to difficulty treating both animal and human infections. Manuka honey has previously been reported to inhibit many bacterial pathogens, including methicillin-resistant Staphylococcus aureus, and is successfully utilized in both clinical and veterinary practice. Here, we evaluated the ability of manuka honey to inhibit strains of S. pseudintermedius grown alone and in combination with antibiotics, as well as its capacity to modulate virulence within multiple S. pseudintermedius isolates. All 18 of the genetically diverse S. pseudintermedius strains sequenced and tested were inhibited by??12% (wt/vol) medical-grade manuka honey, although tolerance to five clinically relevant antibiotics was observed. The susceptibility of the isolates to four of these antibiotics was significantly increased (P ? 0.05) when combined with sublethal concentrations of honey, although sensitivity to oxacillin was decreased. Virulence factor (DNase, protease, and hemolysin) activity was also significantly reduced (P???0.05) in over half of isolates when cultured with sublethal concentrations of honey (13, 9, and 10 isolates, respectively). These findings highlight the potential for manuka honey to be utilized against S. pseudintermedius infections.IMPORTANCE Staphylococcus pseudintermedius is an important member of the skin microbial community in animals and can cause opportunistic infections in both pets and their owners. The high incidence of antimicrobial resistance in S. pseudintermedius highlights that this opportunistic zoonotic pathogen can cause infections which require prolonged and intensive treatment to resolve. Manuka honey has proven efficacy against many bacterial pathogens and is an accepted topical treatment for infections in both veterinary and clinical practice, and so it is a particularly appropriate antimicrobial for use with zoonotic pathogens such as S. pseudintermedius Here, we demonstrate that not only is manuka honey highly potent against novel multidrug-resistant S. pseudintermedius isolates, it also acts synergistically with clinically relevant antibiotics. In addition, manuka honey modulates S. pseudintermedius virulence activity, even at subinhibitory concentrations. In a clinical setting, these attributes may assist in controlling infection, allowing a more rapid resolution and reducing antibiotic use.

SUBMITTER: Brown HL

PROVIDER: S-EPMC7531947 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Antibacterial and Antivirulence Activity of Manuka Honey against Genetically Diverse Staphylococcus pseudintermedius Strains.

Brown Helen L HL Metters Georgie G Hitchings Matthew D MD Wilkinson Thomas S TS Sousa Luis L Cooper Jenna J Dance Harry H Atterbury Robert J RJ Jenkins Rowena R

Applied and environmental microbiology 20201001 20

<i>Staphylococcus pseudintermedius</i> causes opportunistic infections in dogs. It also has significant zoonotic potential, with the emergence of multidrug resistance leading to difficulty treating both animal and human infections. Manuka honey has previously been reported to inhibit many bacterial pathogens, including methicillin-resistant <i>Staphylococcus aureus</i>, and is successfully utilized in both clinical and veterinary practice. Here, we evaluated the ability of manuka honey to inhibi ...[more]

PMID: 32801179

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Project description:Chronic wound infections are a major burden to both society and the health care industry. Bacterial biofilms are the major cause of chronic wound infections and are notoriously recalcitrant to treatments with antibiotics, making them difficult to eradicate. Thus, new approaches are required to combat biofilms in chronic wounds. One possible approach is to use drug combination therapies. Manuka honey has potent broad-spectrum antibacterial activity and has previously shown synergistic activity in combination with antibiotics against common wound pathogens, including Staphylococcus aureus. In addition, manuka honey exhibits anti-biofilm activity, thereby warranting the investigation of its potential as a combination therapy with antibiotics for the topical treatment of biofilm-related infections. Here we report the first use of MacSynergy II to investigate the response of established S. aureus (strain NCTC 8325) biofilms to treatment by combinations of Medihoney (medical grade manuka honey) and conventional antibiotics that are used for preventing or treating infections: rifampicin, oxacillin, fusidic acid, clindamycin, and gentamicin. Using checkerboard microdilution assays, viability assays and MacSynergy II analysis we show that the Medihoney-rifampicin combination was more effective than combinations using the other antibiotics against established staphylococcal biofilms. Medihoney and rifampicin were strongly synergistic in their ability to reduce both biofilm biomass and the viability of embedded S. aureus cells at a level that is likely to be significant in vivo. Other combinations of Medihoney and antibiotic produced an interesting array of effects: Medihoney-fusidic acid treatment showed minor synergistic activity, and Medihoney-clindamycin, -gentamicin, and -oxacillin combinations showed overall antagonistic effects when the honey was used at sub-inhibitory concentration, due to enhanced biofilm formation at these concentrations which could not be counteracted by the antibiotics. However, these combinations were not antagonistic when honey was used at the inhibitory concentration. Confocal scanning laser microscopy confirmed that different honey-antibiotic combination treatments could eradicate biofilms. Our results suggest that honey has potential as an adjunct treatment with rifampicin for chronic wounds infected with staphylococcal biofilms. We also show that MacSynergy II allows a comprehensive examination of the synergistic effects of honey-antibiotic combinations, and can help to identify doses for clinical use.

Project description:Skin infections caused by antibiotic resistant Staphylococcus aureus are a significant health problem worldwide; often associated with high treatment cost and mortality rate. Complex natural products like New Zealand (NZ) manuka honey have been revisited and studied extensively as an alternative to antibiotics due to their potent broad-spectrum antimicrobial activity, and the inability to isolate honey-resistant S. aureus. Previous studies showing synergistic effects between manuka-type honeys and antibiotics have been demonstrated against the growth of one methicillin-resistant S. aureus (MRSA) strain. We have previously demonstrated strong synergistic activity between NZ manuka-type honey and rifampicin against growth and biofilm formation of multiple S. arueus strains. Here, we have expanded our investigation using multiple S. aureus strains and four different antibiotics commonly used to treat S. aureus-related skin infections: rifampicin, oxacillin, gentamicin, and clindamycin. Using checkerboard microdilution and agar diffusion assays with S. aureus strains including clinical isolates and MRSA we demonstrate that manuka-type honey combined with these four antibiotics frequently produces a synergistic effect. In some cases when synergism was not observed, there was a significant enhancement in antibiotic susceptibility. Some strains that were highly resistant to an antibiotic when present alone become sensitive to clinically achievable concentrations when combined with honey. However, not all of the S. aureus strains tested responded in the same way to these combinational treatments. Our findings support the use of NZ manuka-type honeys in clinical treatment against S. aureus-related infections and extend their potential use as an antibiotic adjuvant in combinational therapy. Our data also suggest that manuka-type honeys may not work as antibiotic adjuvants for all strains of S. aureus, and this may help determine the mechanistic processes behind honey synergy.

Dataset Information

Antibacterial and Antivirulence Activity of Manuka Honey against Genetically Diverse Staphylococcus pseudintermedius Strains.

Publications

Antibacterial and Antivirulence Activity of Manuka Honey against Genetically Diverse Staphylococcus pseudintermedius Strains.

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