The convergent evolution of influenza A virus: Implications, therapeutic strategies and what we need to know.

Influenza virus infection, more commonly known as the 'cold flu', is an etiological agent that gives rise to recurrent annual flu and many pandemics. Dated back to the 1918- Spanish Flu, the influenza infection has caused the loss of many human lives and significantly impacted the economy and daily lives. Influenza virus can be classified into four different genera: influenza A-D, with the former two, influenza A and B, relevant to humans. The capacity of antigenic drift and shift in Influenza A has given rise to many novel variants, rendering vaccines and antiviral therapies useless. In light of the emergence of a novel betacoronavirus, the SARS-CoV-2, unravelling the underpinning mechanisms that support the recurrent influenza epidemics and pandemics is essential. Given the symptom similarities between influenza and covid infection, it is crucial to reiterate what we know about the influenza infection. This review aims to describe the origin and evolution of influenza infection. Apart from that, the risk factors entail the implication of co-infections, especially regarding the COVID-19 pandemic is further discussed. In addition, antiviral strategies, including the potential of drug repositioning, are discussed in this context. The diagnostic approach is also critically discussed in an effort to understand better and prepare for upcoming variants and potential influenza pandemics in the future. Lastly, this review encapsulates the challenges in curbing the influenza spread and provides insights for future directions in influenza management.

Metabolic perturbations and key pathways associated with the bacteriostatic activity of Clitoria ternatea flower anthocyanin fraction against Escherichia coli.

Clitoria ternatea flowers are rich in anthocyanins and possess various biological activities. Specifically, the antibacterial mechanism of action of C. ternatea anthocyanins remains unknown and was investigated in Escherichia coli . A time-kill assay was used to assess the antibacterial activity and the metabolic perturbations in E. coli were investigated utilizing liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. Pathway analyses were carried out for metabolites showing ≥2-fold changes. The anthocyanin fraction remarkably reduced the growth of E. coli at 4 h by 95.8 and 99.9 % at minimum inhibitory concentration (MIC) and 2× MIC, respectively. The anthocyanin fraction (MIC) had a bacteriostatic effect and was shown to have perturbed glycerophospholipids (1-acyl-sn-glycero-3-phosphoethanolamine, phosphatidylglycerol, diacylglycerol and cardiolipin), amino acids (valine, tyrosine and isoleucine) and energy (ubiquinone and NAD) metabolites at 1 and 4 h. This study demonstrated significant metabolic perturbations of the glycerophospholipid, amino acid and energy metabolism, with these being the key pathways involved in the bacteriostatic activity of anthocyanins from C. ternatea, which may have promise as bacteriostatic agents for E. coli -related infections.

Anti-Amyloid ß Aggregation Activity and Cell Viability Effect of Betacyanins from Red Pitahaya (Hylocereus polyrhizus) for Alzheimer's Disease.

Betacyanin-rich extract from red beet (Beta vulgaris) was recently reported to inhibit amyloid ß (Aß) aggregation, a main pathological event in Alzheimer's disease. However, the anti-Aß aggregation effect of individual betacyanin isolates has not been reported before. This study investigated the anti-Aß aggregation activity and cytotoxicity of betacyanins from red pitahaya or red dragon fruit (Hylocereus polyrhizus). Betacyanin fraction (IC50 = 16.02 ± 1.15 µg/mL) and individual betacyanin isolates exhibited anti-Aß aggregation activity in a concentration-dependent manner using a thioflavin T fluorescence assay. The highest to lowest IC50 was in the order of betanin (426.30 ± 29.55 µM), phyllocactin (175.22 ± 1.52 µM), and hylocerenin (131.73 ± 5.58 µM), following a trend of increase in functional groups of carboxyl, hydroxyl, and/or carbonyl. Further, the betacyanin fraction of 135.78 µg/mL and below, which were concentrations with an anti-Aß aggregation effect, were validated as non-neurotoxic based on an in vitro cytotoxicity assay using human neuroblastoma (SH-SY5Y) cells. These findings highlight the potential neuroprotective activity of betacyanins for Alzheimer's disease.

Effect of hot water, ultrasound, microwave, and pectinase-assisted extraction of anthocyanins from black goji berry for food application.

Lycium ruthenicum, commonly known as black goji berry, is a rich anthocyanin source containing a high amount of monoacylated anthocyanins. This study investigates the effect of different extraction methods to extract anthocyanins from black goji berry for food application. Different hot water extraction conditions were applied to investigate the effect of specific substrate: solvent ratio (1:15 and 1:20 (w/v)), extraction time (30 and 60 min) and extraction temperature (40, 50 and 60 °C) on the extraction yield, total anthocyanin content (TAC) and the total phenolic content (TPC) of the anthocyanin extracts. Best hot water extraction conditions for obtaining an anthocyanin extract with high TAC (13.8 ± 1.14 mg CGE/g), TPC (69.7 ± 2.50 mg of GAE/g), and extraction yield (48.3 ± 3.25%) consuming less solvent, time and heat were substrate: solvent ratio of 1: 15 (w/v), extraction temperature of 50 °C, and extraction time of 30 min. The effect of pectinase, ultrasound, and microwave on hot water extraction of anthocyanins from black goji berry was investigated using the best conditions for hot water extraction. Pectinase-assisted extraction [1.5% (w/v) pectinase, substrate: solvent ratio of 1:15 (w/v) at 50 °C for 30 min] was the best extraction method to extract black goji berry anthocyanins demonstrating higher extraction yield, TAC, TPC, and the highest percentage of petunidin-3-O-(trans-p-coumaroyl)-rutinoside-5-O-glucoside.

Cannabis as antivirals.

Cannabis is a plant notorious for its psychoactive effect, but when used correctly, it provides a plethora of medicinal benefits. With more than 400 active compounds that have therapeutic properties, cannabis has been accepted widely as a medical treatment and for recreational purposes in several countries. The compounds exhibit various clinical benefits, which include, but are not limited to, anticancer, antimicrobial, and antioxidant properties. Among the vast range of compounds, multiple research papers have shown that cannabinoids, such as cannabidiol and delta-9-tetrahydrocannabinol, have antiviral effects. Recently, scientists found that both compounds can reduce severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral infection by downregulating ACE2 transcript levels and by exerting anti-inflammatory properties. These compounds also act as the SARS-CoV-2 main protease inhibitors that block viral replication. Apart from cannabinoids, terpenes in cannabis plants have also been widely explored for their antiviral properties. With particular emphasis on four different viruses, SARS-CoV-2, human immunodeficiency virus, hepatitis C virus, and herpes simplex virus-1, this review discussed the role of cannabis compounds in combating viral infections and the potential of both cannabinoids and terpenes as novel antiviral therapeutics.

Growth and survival of Bifidobacterium breve and Bifidobacterium longum in various sugar systems with fructooligosaccharide supplementation.

This study aims to investigate the effect of fructooligosaccharide (FOS) (0.5, 1, 2, 3, and 4%) supplementation on the growth and survival of Bifidobacterium breve and Bifidobacterium longum in glucose, fructose, lactose, and sucrose (2, 3, and 4%) systems with 24-h growth and 10-day survival assays at 37 °C. FOS supplementation showed a higher growth-promoting effect on B. longum than B. breve in various sugar systems. The highest percentage of increase in growth index, 78.5%, was observed with 4% sucrose supplemented with 0.5% FOS in B. longum. In comparison, the highest percentage increase in growth index, 5.6 and 6.6%, was observed in the presence of 2% glucose and 4% lactose supplemented with 0.5% FOS in B. breve. In survival assay, FOS supplementation (0.5-4%) in a 2% lactose system showed the highest positive effect on the cell viability of B. longum on day-10. As for B. breve, FOS supplementation (1 and 2%) in the 2% sucrose system showed the highest positive effect on the cell viability, followed by FOS supplementation (0.5, 3, and 4%) in 2% sucrose and FOS supplementation (3 and 4%) in 2% lactose on day-10. This study demonstrated that the efficacy of FOS supplementation was depended on its concentration, sugar system and its concentration, and Bifidobacterium strain. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05361-z.

Antioxidant, cytotoxic, and antibacterial activities of Clitoria ternatea flower extracts and anthocyanin-rich fraction.

Clitoria ternatea flower is a traditional medicinal herb that has been used as a natural food colourant. As there are limited studies on investigating the bioactivities of the anthocyanin-rich fraction of Clitoria ternatea flower, this study aimed to determine an efficient column chromatography method to obtain the anthocyanin-rich fraction from this flower and characterise its composition, antioxidant, antibacterial, and cytotoxic activities. Amberlite XAD-16 column chromatography was more efficient in enriching the total anthocyanin content (TAC) of the fraction with the highest TAC to total phenolic content (TPC) ratio of 1:6 than that using C18-OPN. A total of 11 ternatin anthocyanins were characterised in the anthocyanin-rich fraction by LC-MS analysis. The antioxidant activity of the anthocyanin-rich fraction was more potent in the chemical-based assay with an IC50 value of 0.86 ± 0.07 mg/mL using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay than cellular antioxidant assay using RAW 264.7 macrophages. In vitro cytotoxicity assay using human embryonic kidney HEK-293 cell line showed the anthocyanin-rich fraction to be more toxic than the crude extracts. The anthocyanin-rich fraction had more potent antibacterial activity than the crude extracts against Bacillus cereus, Bacillus subtilis, and Escherichia coli. The anthocyanin-rich fraction of C. ternatea has the potential to be used and developed as a functional food ingredient or nutraceutical agent.

Antimicrobial betalains.

Betalains are nitrogen-containing plant pigments that can be red-violet (betacyanins) or yellow-orange (betaxanthins), currently employed as natural colourants in the food and cosmetic sectors. Betalains exhibit antimicrobial activity against a broad spectrum of microbes including multidrug-resistant bacteria, as well as single-species and dual-species biofilm-producing bacteria, which is highly significant given the current antimicrobial resistance issue reported by The World Health Organization. Research demonstrating antiviral activity against dengue virus, in silico studies including SARS-CoV-2, and anti-fungal effects of betalains highlight the diversity of their antimicrobial properties. Though limited in vivo studies have been conducted, antimalarial and anti-infective activities of betacyanin have been observed in living infection models. Cellular mechanisms of antimicrobial activity of betalains are yet unknown; however existing research has laid the framework for a potentially novel antimicrobial agent. This review covers an overview of betalains as antimicrobial agents and discussions to fully exploit their potential as therapeutic agents to treat infectious diseases.

Antibiofilm properties of Clitoria ternatea flower anthocyanin-rich fraction towards Pseudomonas aeruginosa.

In Asia, Clitoria ternatea flowers are commonly used as a traditional medicinal herb and as a food colourant. Their bioactive compounds have anti-inflammatory, anti-microbial and anti-biofilm activities. Pseudomonas aeruginosa is one of the major pathogens that cause biofilm-associated infections resulting in an increase in antimicrobial resistance. Hence, the aim of this study was to investigate if the anti-biofilm properties of the anthocyanin-rich fraction of C. ternatea flowers were effective against P. aeruginosa . The effect of the anthocyanin-rich fraction of C. ternatea flowers on P. aeruginosa biofilms formed on a polystyrene surface was determined using the crystal violet assay and scanning electron microscopy (SEM). The anthocyanin-rich fraction reduced biofilm formation by four P. aeruginosa strains with a minimum biofilm inhibitory concentration value ranging between 0.625 and 5.0 mg ml-1. We further show that the biofilm-inhibiting activity of C. ternatea flowers is not due to the flavonols but is instead attributed to the anthocyanins, which had significant biofilm inhibitory activity (64.0±1.1 %) at 24 h in a time-response study. The anthocyanin-rich fraction also significantly reduced bacterial attachment on the polystyrene by 1.1 log c.f.u. cm-2 surface based on SEM analysis. Hence, anthocyanins from C. ternatea flowers have potential as an agent to decrease the risk of biofilm-associated infections.

Sources and relative stabilities of acylated and nonacylated anthocyanins in beverage systems.

Anthocyanins are considered as the largest group of water-soluble pigments found in the vacuole of plant cells, displaying range of colors from pink, orange, red, purple and blue. They belong to flavonoids, a polyphenolic subgroup. Application of anthocyanins in food systems as natural food colourants is limited due to the lack of stability under different environmental conditions such as light, pH, heat etc. Anthocyanins esterified with one or more acid groups are referred as acylated anthocyanins. Based on the presence or absence of acyl group, anthocyanins are categorized as acylated and nonacylated anthocyanins. Acylated anthocyanins are further classified as mono, di, tri, tetra acylated anthocyanins according to the number of acyl groups present in the anthocyanin. This review classifies common anthocyanin sources into non-acylated, mono-, di-, tri- and tetra-acylated anthocyanins based on the major anthocyanins present in these sources. The relative stabilities of these anthocyanins with respect to thermal, pH and photo stress in beverage systems are specifically discussed. Common anthocyanin sources such as elderberry, blackberry, and blackcurrant mainly contain nonacylated anthocyanins. Red radish, purple corn, black carrot also mainly contain mono acylated anthocyanins. Red cabbage and purple sweet potato have both mono and diacylated anthocyanins. Poly acylated anthocyanins show relatively higher stability compared with nonacylated and monoacylated anthocyanins. Several techniques such as addition of sweeteners, co-pigmentation and acylation techniques could enhance the stability of nonacylated anthocyanins. Flowers are main sources of polyacylated anthocyanins having higher stability, yet they have not been commercially exploited for their anthocyanins.

Opportunities for the marine carotenoid value chain from the perspective of fucoxanthin degradation.

Marine carotenoids, particularly fucoxanthin, are emerging in the food value chain and gaining traction for their role in delivering health benefits. Unfortunately, the very feature of fucoxanthin which confers its bioactivities also renders it unstable. It is imperative to have a better understanding on the mechanisms involved to mitigate undesirable losses. This paper presented a review on fucoxanthin bioactivities, stability, and opportunities along the value chain specifically during processing, storage, and transportation conditions. For bioactivities, fucoxanthin demonstrated antioxidant, anti-inflammatory, anti-cancer, anti-obese, antidiabetic as well as skin protective activities. Conditions such as low pH (pH 2 to 4), high temperature (beyond 100 °C), presence of light (light intensity of 6.9 to 42 µmol/m2/s) and continuous air exposure caused fucoxanthin instability which lead to its degradation. This review acts as an antecedent by providing insights and enabling informed decisions for managing unaccounted risks within the carotenoid value chains to minimize losses.

Fermentation of red pitahaya extracts using Lactobacillus spp. and Saccharomyces cerevisiae for reduction of sugar content and concentration of betacyanin content.

A study was conducted to concentrate the betacyanin in red pitahaya extracts by removing the coexisting sugars by fermentation. Four lactic acid bacteria (Lactobacillus acidophilus, L. casei, L. rhamnosus and L. plantarum) and a yeast species (Saccharomyces cerevisiae) were screened to determine their efficiency to reduce sugar content in red pitahaya extracts for concentration of their betacyanin content. A reduction of sugar content (19.8-56.4%) and increase in the yield of betacyanins were observed in all extracts as compared to the control, which was not innoculated with any microorganisms after 1 day of fermentation. The lowest total sugar content (26.40 g/L) was observed in extracts fermented by S. cerevisiae. Extracts fermented by S. cerevisiae also showed greater numbers of microbial cells (10.75 log CFU/mL) and a lower pH value (3.54) compared to those (6.89-8.48 log CFU/mL and pH 4.64-5.42) of the Lactobacillus spp. after 1 day of fermentation. An optimization step using response surface methodology (RSM) was then conducted using S. cerevisiae. Temperature, time and agitation speed were found to have a significant effect on the total sugar content and BC of concentrated betacyanins from red pitahaya, while the yield of betacyanins was significantly influenced by temperature and agitation speed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05116-2.

Current vaccine approaches and emerging strategies against herpes simplex virus (HSV).

Introduction: Vaccine development for the disease caused by the herpes simplex virus (HSV) has been challenging over the years and is always in dire need of novel approaches for prevention and cure. To date, the HSV disease remains incurable and challenging to prevent. The disease is extremely widespread due to its high infection rate, resulting in millions of infection cases worldwide.Areas covered: This review first explains the diverse forms of HSV-related disease presentations and reports past vaccine history for the disease. Next, this review examines current and novel HSV vaccine approaches being studied and tested for efficacy and safety as well as vaccines in clinical trial phases I to III. Modern approaches to vaccine design using bioinformatics are described. Finally, we discuss measures to enhance new vaccine development pipelines for HSV.Expert opinion: Modernized approaches using in silico analysis and bioinformatics are emerging methods that exhibit potential for producing vaccines with enhanced targets and formulations. Although not yet fully established for HSV disease, we describe current studies using these approaches for HSV vaccine design to shed light on these methods. In addition, we provide up-to-date requirements of immunogenicity, adjuvant selection, and routes of administration.

Extraction methods of butterfly pea (Clitoria ternatea) flower and biological activities of its phytochemicals.

Clitoria ternatea or commonly known as 'Butterfly pea' has been used traditionally in Ayurvedic medicine in which various parts of the plants are used to treat health issues such as indigestion, constipation, arthritis, skin diseases, liver and intestinal problems. The flowers of C. ternatea are used worldwide as ornamental flowers and traditionally used as a food colorant. This paper reviews the recent advances in the extraction and biological activities of phytochemicals from C. ternatea flowers. The application of maceration or ultrasound assisted extraction greatly increased the yield (16-247% of increase) of phytochemicals from C. ternatea flowers. Various phytochemicals such as kaempferol, quercetin and myricetin glycosides as well as anthocyanins have been isolated from C. ternatea flowers. Clitoria ternatea flower extracts were found to possess antimicrobial, antioxidant, anti-inflammatory, cytotoxic and antidiabetic activities which are beneficial to human health. Clitoria ternatea flower is a promising candidate for functional food applications owing to its wide range of pharmacotherapeutic properties as well as its safety and effectiveness.

Betacyanins from Hylocereus polyrhizus: pectinase-assisted extraction and application as a natural food colourant in ice cream.

The effect of solvent, substrate-to-solvent ratio and concentration of pectinase on the extraction of betacyanins from the pulp of red pitahaya (Hylocereus polyrhizus) was evaluated with respect to yield, betacyanin content (BC) and total sugar content. The application of betacyanins from red pitahaya in ice cream was then evaluated by comparison to a commercial colourant, E-162. Without the use of pectinase, the highest yields (9.11 ± 0.35%) of betacyanins were obtained using 95% ethanol at a substrate-to-solvent ratio of 1:1. With the use of pectinase at a concentration of 1.5%, the highest yield (17.11-17.45%) of betacyanins were obtained using water as a solvent at a substrate-to-solvent ratio of 1:1 and 1:2. Pectinase treatment (1.5-2.5%) using water as a solvent yielded betacyanins with the highest BC (126.47-130.83 g kg-1) and lowest total sugar content (57.85-59.74 g kg-1). The BC and total colour changes were similar in ice cream containing betacyanins from red pitahaya and E-162 throughout the 21-days of frozen storage at -18 °C. Betacyanins from red pitahaya or E-162 enhanced the antioxidant properties of ice cream. The sensory evaluation of ice cream containing betacyanins from red pitahaya showed a better colour acceptability than E-162.

Anthocyanins From Clitoria ternatea Flower: Biosynthesis, Extraction, Stability, Antioxidant Activity, and Applications.

Clitoria ternatea plant is commonly grown as an ornamental plant and possesses great medicinal value. Its flower is edible and also known as blue pea or butterfly pea flower. The unique feature of anthocyanins present in blue pea flowers is the high abundance of polyacylated anthocyanins known as ternatins. Ternatins are polyacylated derivatives of delphinidin 3,3',5'-triglucoside. This review covers the biosynthesis, extraction, stability, antioxidant activity, and applications of anthocyanins from Clitoria ternatea flower. Hot water extraction of dried or fresh petals of blue pea flower could be employed successfully to extract anthocyanins from blue pea flower for food application. Blue pea flower anthocyanins showed good thermal and storage stability, but less photostability. Blue pea flower anthocyanins also showed an intense blue colour in acidic pH between pH 3.2 to pH 5.2. Blue pea flower anthocyanin extracts demonstrate significant in vitro and cellular antioxidant activities. Blue pea flower anthocyanins could be used as a blue food colourant in acidic and neutral foods. The incorporation of blue pea flower anthocyanins in food increased the functional properties of food such as antioxidant and antimicrobial properties. Blue pea flower anthocyanins have also been used in intelligent packaging. A comparison of blue pea flower anthocyanins with two other natural blue colouring agents used in the food industry, spirulina or phycocyanin and genipin-derived pigments is also covered. Anthocyanins from blue pea flowers are promising natural blue food colouring agent.

Betacyanin-inhibited biofilm formation of co-culture of Staphylococcus aureus and Pseudomonas aeruginosa on different polymer surfaces.

Staphylococcus aureus and Pseudomonas aeruginosa are bacteria that cause biofilm-associated infections. The aim of this study was to determine the activity of combined betacyanin fractions from Amaranthus dubius (red spinach) and Hylocereus polyrhizus (red pitahaya) against biofilms formed by co-culture of S. aureus and P. aeruginosa on different polymer surfaces. Various formulations containing different concentrations of the betacyanin fractions were investigated for biofilm-inhibiting activity on polystyrene surfaces using crystal violet assay and scanning electron microscopy. A combination of each betacyanin fraction (0.625 mg mL-1) reduced biofilm formation of five S. aureus strains and four P. aeruginosa strains from optical density values of 1.24-3.84 and 1.25-3.52 to 0.81-2.63 and 0.80-1.71, respectively. These combined fractions also significantly inhibited dual-species biofilms by 2.30 and reduced 1.0-1.3 log CFU cm-2 bacterial attachment on polymer surfaces such as polyvinyl chloride, polyethylene, polypropylene and silicone rubber. This study demonstrated an increase in biofilm-inhibiting activity against biofilms formed by two species using combined fractions than that by using single fractions. Betacyanins found in different plants could collectively be used to potentially decrease the risk of biofilm-associated infections caused by these bacteria on hydrophobic polymers.

Antiviral activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against dengue virus type 2 (GenBank accession no. MH488959).

This study investigated the antiviral activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against dengue virus type 2 (DENV-2). The pulp of red pitahaya and the leaves of red spinach were extracted using methanol followed by sub-fractionation and Amberlite XAD16N column chromatography to obtain betacyanin fractions. The half maximum cytotoxicity concentration for betacyanin fractions from red pitahaya and red spinach on Vero cells were 4.346 and 2.287 mg ml-1, respectively. The half-maximal inhibitory concentration (IC50) of betacyanin fraction from red pitahaya was 125.8 µg ml-1 with selectivity index (SI) of 5.8. For betacyanin fraction from red spinach, the IC50 value was 14.62 µg ml-1 with SI of 28.51. Using the maximum non-toxic betacyanin concentration, direct virucidal effect against DENV-2 was obtained from betacyanin fraction from red pitahaya (IC50 of 126.70 µg ml-1; 95.0 % virus inhibition) and red spinach (IC50 value of 106.80 µg ml-1; 65.9 % of virus inhibition). Betacyanin fractions from red pitahaya and red spinach inhibited DENV-2 in vitro.

Betanin from beetroot enhanced survival of Caenorhabditis elegans infected with methicillin-resistant Staphylococcus aureus

@#Aims: Betanin is a red plant pigment belonging to the group called betalain. This present study aimed at investigating the effect betanin from beetroot (Beta vulgaris subsp. vulgaris) as a potential anti-infective agent against methicillinresistant Staphylococcus aureus (MRSA) using a Caenorhabditis elegans infection model. Methodology and results: The minimum inhibitory concentration of betanin against MRSA strain ATCC 33591 was determined to establish the non-inhibitory concentration. The minimum inhibitory concentration of betanin against MRSA was > 20 mg/mL. C. elegans were then infected with MRSA and treated with betanin at different concentrations (100, 200, 300 and 400 µg/mL). Betanin at 200 µg/mL significantly improved worm survival following infection whereby the mean time to death was extended about 76 h upon treatment. Intestinal colonization by MRSA of worms exposed to betanin extract was similar to non-betanin-treated infected worms. Conclusion, significance and impact of study: The enhanced survival of MRSA-infected worms upon betanin treatment was not a result of the activation of the host antimicrobial mechanism. Betanin from beetroot can be potentially used as a natural anti-infective agent as a mean to reduce antimicrobial resistance of S. aureus or used in combination with established antimicrobials to increase their effectiveness.