Tomatidine acts in synergy with aminoglycoside antibiotics against multiresistant Staphylococcus aureus and prevents virulence gene expression

Mitchell, Gabriel; Lafrance, Mylène; Boulanger, Simon; Séguin, David Lalonde; Guay, Isabelle; Gattuso, Mariza; Marsault, Éric; Bouarab, Kamal; Malouin, François

doi:10.1093/jac/dkr510

Cited by 90 publications

(86 citation statements)

References 42 publications

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“…Anti-infection strategies combining antibiotics with antivirulence and antiadhesion compounds could thus reduce the emergence of multiresistant pathogens (36,46,47). Investigation of antibiofilm molecules such as G2cps in relevant in vivo models (48) will allow evaluations of the therapeutic significance of controlling pathogen surface adhesion and colonization, while avoiding selection for new types of resistance in clinical and industrial situations.…”

Section: Discussionmentioning

confidence: 99%

Escherichia coli Resistance to Nonbiocidal Antibiofilm Polysaccharides Is Rare and Mediated by Multiple Mutations Leading to Surface Physicochemical Modifications

Travier

Rendueles

Ferrières

et al. 2013

Antimicrob Agents Chemother

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Antivirulence strategies targeting bacterial behavior, such as adhesion and biofilm formation, are expected to exert low selective pressure and have been proposed as alternatives to biocidal antibiotic treatments to avoid the rapid occurrence of bacterial resistance. Here, we tested this hypothesis using group 2 capsule polysaccharide (G2cps), a polysaccharidic molecule previously shown to impair bacterium-surface interactions, and we investigated the nature of bacterial resistance to a nonbiocidal antibiofilm strategy. We screened an Escherichia coli mutant library for an increased ability to form biofilm in the presence of G2cps, and we identified several mutants displaying partial but not total resistance to this antibiofilm polysaccharide. Our genetic analysis showed that partial resistance to G2cps results from multiple unrelated mutations leading to modifications in surface physicochemical properties that counteract the changes in ionic charge and Lewis base properties induced by G2cps. Moreover, some of the identified mutants harboring improved biofilm formation in the presence of G2cps were also partially resistant to other antibiofilm molecules. This study therefore shows that alterations of bacterial surface properties mediate only partial resistance to G2cps. It also experimentally validates the potential value of nonbiocidal antibiofilm strategies, since full resistance to antibiofilm compounds is rare and potentially unlikely to arise in clinical settings.

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Section: Discussionmentioning

confidence: 99%

Escherichia coli Resistance to Nonbiocidal Antibiofilm Polysaccharides Is Rare and Mediated by Multiple Mutations Leading to Surface Physicochemical Modifications

Travier

Rendueles

Ferrières

et al. 2013

Antimicrob Agents Chemother

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“…10,11 Recently, several research groups reported that staphyloxanthin is one of the important virulent factors of S. aureus. 12,13 Staphyloxanthin acts as an antioxidant with its numerous conjugated double bonds, which enable S. aureus to survive by detoxification of host-generated reactive oxgen species such as O 2 À , H 2 O 2 and HOCl. 14,15 Staphyloxanthin develops in the cell membrane of S. aureus and is associated with enhancing S. aureus survival and infection.…”

Section: Resultsmentioning

confidence: 99%

“…) 13. C-NMR (100 MHz, CD 3 OD) d: 166.1, 163.3, 135.6, 134.2, 129.7, 128.7, 128.5, 114.6, 112.9, 99.0, 58.8, 57.0, 56.5, 41.6, 39.9, 29.6, 19.6.…”

mentioning

confidence: 99%

Synthesis and biological activity of Citridone A and its derivatives

et al. 2014

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Citridone A (1), originally isolated as a potentiator of antifungal miconazole activity from a fungal culture broth, has a phenyl-R-furopyridone structure. Because of its unique ring structure, 11 derivatives were chemically synthesized and their biological activity was evaluated. Derivatives 17, 20 and 21 potentiated miconazole activity against Candida albicans. Furthermore, 1, 14, 20 and 21 were found to inhibit yellow pigment production in methicillin-resistant Staphylococcus aureus.

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“…Quantification of the δ-toxin reflects the agr activity of S. aureus (7, 8). δ-hemolysin is a 26-amino-acid peptide and heat-stabile protein produced by 97% of S. aureus strains.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Ferula assa-foetida L and Carum copticum Hydroalcoholic Extract on the Expression Levels of Staphylococcus aureus Genes Involved in Quorum Sensing

Jomehpour

Eslami

Khalili

2016

Jundishapur J Microbiol

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BackgroundQuorum sensing is a microbial cell-to-cell communication process. Quorum sensing bacteria produce and release extracellular messenger molecules called autoinducers. Gram-positive and Gram-negative, homoserine lactones, and oligopeptides are autoinducers used to communicate and regulate gene expression.ObjectivesThe goal of this study was to assess the impact of subinhibitory concentrations of Ferula assa-foetida l oleo-gum resin and Carum copticum fruit on the expression of tst and hld genes of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) strains.MethodsThis analytical study was performed using standard strains of MRSA (ATCC 33591) and MSSA (ATCC 29213). Suspensions of MRSA and MSSA bacteria were incubated at 37°C for 7 and 16 hours in the presence of ethanol extracts from F. assa-foetida and C. copticum. The expression of the hld and tst genes was then assessed using the real-time PCR protocol and SYBR Green Master Mix. The data analysis was carried out using the 2-ΔΔCT method.ResultsThe hld gene expression (RNAIII) of MRSA after 7 and 16 hours of exposure to the sMIC of the F. assa-foetida extract showed a fold change of -1 and 0.08, respectively, in comparison with controls. After 7 and 16 hours of exposure to the sMIC of the C. copticum extract, the fold change was -0.23 and -0.27, respectively. After exposure to the sMIC of the C. copticum extract for 16 hours, the fold change in the expression of the tst (TSST-1) MSSA gene was 0.37 lower than that of the control sample.ConclusionsThe results indicate that sMICs of ethanol extracts from F. assa-foetida and C. copticum can be used to control the expression of virulence genes in pathogenic bacteria, such as MRSA and MSSA.

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Tomatidine acts in synergy with aminoglycoside antibiotics against multiresistant Staphylococcus aureus and prevents virulence gene expression

Abstract: These results show that tomatidine is an aminoglycoside potentiator that also acts as an anti-virulence agent targeting both antibiotic-susceptible and antibiotic-resistant S. aureus.

Cited by 90 publications

References 42 publications

Escherichia coli Resistance to Nonbiocidal Antibiofilm Polysaccharides Is Rare and Mediated by Multiple Mutations Leading to Surface Physicochemical Modifications

Escherichia coli Resistance to Nonbiocidal Antibiofilm Polysaccharides Is Rare and Mediated by Multiple Mutations Leading to Surface Physicochemical Modifications

Synthesis and biological activity of Citridone A and its derivatives

The Effect of Ferula assa-foetida L and Carum copticum Hydroalcoholic Extract on the Expression Levels of Staphylococcus aureus Genes Involved in Quorum Sensing

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