Eradication and Sensitization of Methicillin Resistant Staphylococcus aureus to Methicillin with Bioactive Extracts of Berry Pomace

Abstract

The therapeutic roles of phenolic blueberry (Vaccinium corymbosum) and blackberry (Rubus fruticosus) pomace (commercial byproduct) extracts (BPE) and their mechanism of actions were evaluated against methicillin resistant Staphylococcus aureus (MRSA). Five major phenolic acids of BPE, e.g., protocatechuic, p. coumaric, vanillic, caffeic, and gallic acids, as well as crude BPE completely inhibited the growth of vegetative MRSA in vitro while BPE+methicillin significantly reduced MRSA biofilm formation on plastic surface. In addition, BPE restored the effectiveness of methicillin against MRSA by down-regulating the expression of methicillin resistance (mecA) and efflux pump (norA, norB, norC, mdeA, sdrM, and sepA) genes. Antibiogram with broth microdilution method showed that MIC of methicillin reduced from 512 μg/mL to 4 μg/mL when combined with only 200 μg Gallic Acid Equivalent (GAE)/mL of BPE. Significant reduction in MRSA adherence to and invasion into human skin keratinocyte Hek001 cells were also noticed in the presence of BPE. BPE induced anti-apoptosis and anti-autophagy pathways through overexpression of Bcl-2 gene and down-regulation of TRADD and Bax genes (inducers of apoptosis pathway) in Hek001 cells. In summary, novel and sustainable prophylactic therapy can be developed with BPE in combination with currently available antibiotics, especially methicillin, against skin and soft tissue infections with MRSA.

Characterization of Phenolic Acid Antimicrobial and Antioxidant Structure–Property Relationships

“…Staph. aureus [24] E. coli [10] Not effective against E. coli [22] Relatively ineffective [16] Syringic acid Some efficacy against E. coli [25] 1.3X trolox efficacy [16] Protocatechuic acid Methicillin-resistant Staph. aureus [24,28] E. coli [10,28]…”

“…aureus [26] E. coli [26] 6X trolox efficacy [16] Caffeic acid Methicillin-resistant Staph. aureus [24] E. coli [10] Scavenged 59% of H 2 O 2 [15] 4X trolox efficacy [16] Benzoic acid Not effective against Staph. aureus [11] Multidrug-resistant E. coli [11] N/A 4-hydroxy-benzoic acid Staph.…”

Linoleic Acids Overproducing Lactobacillus casei Limits Growth, Survival, and Virulence of Salmonella Typhimurium and Enterohaemorrhagic Escherichia coli

“…The Center for Disease Control and Prevention (CDC) estimated that in the United States alone, 48 million illnesses (approximately 1 in 6 Americans), more than 128 thousand hospitalizations, and thousands of deaths are caused by foodborne infections each year ( Hoffmann et al, 2012 ; Adams et al, 2015 , 2016 , 2017 ). The most predominant causative foodborne infectious agents, including Salmonella enterica serovar Typhimurium (ST) and EHEC, commonly colonize in farm animals’ guts, and during normal food production or processing, these pathogens often cross-contaminate meat products ( Peng et al, 2014 , 2016 , 2018b ; Salaheen et al, 2016b , 2017 ).…”

Antimicrobial and Antivirulence Impacts of Phenolics on Salmonella Enterica Serovar Typhimurium

“…Plant extracts are promising candidates because the diversity of bioactive compounds they contain are thought to exert multiple adverse actions over a given bacterium, reducing the risk of developing resistance [ 56 ]. However, understanding the mechanisms of action of the individual constituents of these extracts will allow for their use in a more guided and efficient manner, even allowing for the possibility of rescuing conventional antibiotics [ 57 , 58 ]. The antimicrobial efficiency of individual phenolic compounds is not as effective as that of leading antibiotics or to that of many raw plant extracts, but in the future may provide alternatives to infections considered as untreatable by antibiotics.…”