Synergistic antibacterial effects of herbal extracts and antibiotics on methicillin-resistant Staphylococcus aureus: A computational and experimental study

Abstract

Antibiotic resistant is a well-known threat to global health and methicillin-resistant Staphylococcus aureus is one of the most significant ones. These resistant bacteria kill thousands of people every year and therefore a new effective antimicrobial treatment is necessary. This study identified the herbs and their associated bioactive ingredients that can potential the effects of current antibiotics. These herbs have long history of human usage in China and have well-defined monograph in the Chinese Pharmacopeia. These indicate their relatively high clinical safety and may have a quicker drug development process than that of a new novel antibiotic. Based on the results of this study, the authors will perform further in vitro and animal studies, aiming to accumulate significant data for the application of clinical trial. AbstractAntibiotic resistance has become a serious global concern, and the discovery of antimicrobial herbal constituents may provide valuable solutions to overcome the problem. In this study, the effects of therapies combining antibiotics and four medicinal herbs on methicillinresistant Staphylococcus aureus (MRSA) were investigated. Specifically, the synergistic effects of Magnolia officinalis, Verbena officinalis, Momordica charantia, and Daphne genkwa in combination with oxacillin or gentamicin against methicillin-resistant (ATCC43300) and methicillin-susceptible (ATCC25923) S. aureus were examined. In vitro susceptibility and synergistic testing were performed to measure the minimum inhibitory concentration and fractional inhibitory concentration (FIC) index of the antibiotics and medicinal herbs against MRSA and methicillin-susceptible S. aureus. To identify the active constituents in producing these synergistic effects, in silico molecular docking was used to investigate the binding affinities of 139 constituents of the four herbs to the two common MRSA inhibitory targets, penicillin binding proteins 2a (PBP2a) and 4 (PBP4). The physicochemical and absorption, distribution, metabolism, and excretion properties and drug safety profiles of these compounds were also analyzed. D. genkwa extract potentiated the antibacterial effects of oxacillin against MRSA, as indicated by an FIC index value of 0.375. M. officinalis and V. officinalis produced partial synergistic effects when combined with oxacillin, whereas M. charantia was found to have no beneficial effects in inhibiting MRSA. Overall, tiliroside, pinoresinol, magnatriol B, and momorcharaside B were predicted to be PBP2a or PBP4 inhibitors with good drug-like properties. This study identifies compounds that deserve further investigation with the aim of developing therapeutic agents to modulate the effect of antibiotics on MRSA.

A Review on the Dietary Flavonoid Tiliroside

“…The outcomes showed that the addition of 64 μg/mL of tiliroside may lower the MIC of tested antibiotics by 2 (ofloxacin) to 128 (acriflavine) times (Falcão‐Silva, Silva, Souza, & Siqueira‐Junior, ). As was observed in computational studies, tiliroside can presumably also inhibit penicillin‐binding proteins 2a (PBP2a) and 4 (PBP4), produced by methicillin‐resistant S. aureus (Kuok et al., ) The drug resistance of various microorganisms was apparent from the beginning of antibiotic development. However, the disturbing and dangerous appearance of rising numbers of resistant bacteria has recently been noted (Fair & Tor, ).…”

Plant Secondary Metabolites in the Battle of Drugs and Drug-Resistant Bacteria: New Heroes or Worse Clones of Antibiotics?

“…For example, Staphylococcus aureus, one of the most dangerous human pathogens, causing a wide range of infections from mild skin diseases to life-threatening endocarditis [23,84]. The greatest problem is the methicillin-resistant (MRSA) S. aureus strain, which is the fastest-evolving pathogen in the last decade and one of the most common causes of multidrug-resistant infections with significant morbidity and mortality, especially in developing countries [85]. After identifying methicillin-resistant strains, vancomycin and quinolones antibiotics have been used as alternative drugs of choice in staphylococcal infections therapy [86].…”

Non-microbial Natural Products That Inhibit Drug-Resistant Staphylococcus aureus

“…Both PBP2a protein and mecA gene are emerging antimicrobial targets for therapeutics development [159,160]. Various type of natural products targeting mecA gene or PBP2a have also been reported, these compounds include curcumin [161], tiliroside, pinoresinol, magnatriol B, and momorcharaside B [151], Acalypha wilkesiana (evergreen shrub) extract [136], and Poncirus trifoliata extract [139]. In combination with antibiotics, several natural compounds have also reduced the expression of PBP2a.…”