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Overuse or misuse of broad-spectrum antibiotics increases the risk of the emergence of antibiotic-resistant bacteria, which increases the possibility of antimicrobial-resistant (AMR) bacterial infections, and subsequently raises healthcare costs. The excessive use of broad-spectrum antibiotics has also been linked to increased death rates, whilst the benefits that they offer against antibiotic-resistant bacterial pathogens are minimal. Patients infected with antibiotic-resistant bacterial pathogens frequently receive inadequate antimicrobial therapies due to a lack of effective options than those with non-resistant infections, resulting in poor health outcomes and longer recovery times, especially among patients who are critically ill. Broad-spectrum antibiotics also disturb the gut microbiome, which is increasingly recognized as a regulator of immune health. This study offers insights into the use of targeted antimicrobial therapies for bacterial infections, focusing on strategies that mitigate the risk of antibiotic resistance and unwanted side effects associated with the use of broad-spectrum antibiotics. We focus on identifying the genotype and phenotype of bacterial pathogens and then using either nanoparticle-based, vaccine-based, bacteriophage-based, monoclonal antibody-based, and CRISPR-based targeted therapies to directly kill those pathogens and reduce collateral damage. Furthermore, the mechanisms of action of these targeted therapies and their advantages and disadvantages are discussed. [ABSTRACT FROM AUTHOR]

Background: Nigella sativa L., Anongessius latifolia (Roxb. ex DC.) Wall. ex Euill. and Perr. and shilajit have been used traditionally to treat numerous infectious diseases, including many caused by bacterial pathogens. However, extracts of these traditionally medicines have been poorly studied and are yet to be tested for the ability to inhibit the growth of bacterial triggers of multiple sclerosis and rheumatic fever. Materials and Methods: Antimicrobial activity of selected plant extracts was assessed using disc diffusion and liquid dilution minimum inhibitory concentration (MIC) assays against some bacterial triggers of multiple sclerosis and rheumatic fever. Interactions between the extracts and conventional antibiotics were studied and classified using the sum of the fractional inhibitory concentration (SFIC). The toxicity of the individual samples and the combinations was assessed using the artemia lethality assay (ALA) assay. Results: The methanolic A. latifolia extract displayed notable antibacterial activity against the bacterial triggers of multiple sclerosis (A. baylyi and P. aeruginosa), and rheumatic fever (S. pyogenes). Furthermore, combining the methanolic A. latifolia extract with tetracycline and chloramphenicol resulted in potentiation of the inhibitory activity against P. aeruginosa and S. pyogenes. None of the individual components (nor the combinations) were toxic in the ALA assay. Conclusion: The A. latifolia methanolic displayed clinically relevant antibacterial activity against A. baylyi, P. aeruginosa and S. pyogenes when tested alone. Furthermore, that extract also potentiated the activity of tetracycline and chloramphenicol against some bacteria. The lack of toxicity of the extracts and combinations indicates that these combinations may provide leads in the development of new therapies to prevent and treat the autoimmune diseases multiple sclerosis and rheumatic fever. [ABSTRACT FROM AUTHOR]

Background: The increased prevalence of antibiotic-resistant bacterial pathogens has substantially decreased the efficacy of some antibiotics and has rendered others completely ineffective. Widespread bacterial resistance to ß-lactam antibiotics (including resistance to the second-generation drug methicillin) is particularly concerning and new antibiotic therapies are urgently needed. Materials and Methods: The antibacterial activity of commercially sourced water-soluble Eucalyptus major and Melaleuca alternifolia leaf solutions was screened against ß-lactam resistant and sensitive bacterial strains of Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus using disc diffusion assays. The activity was quantified by broth microdilution minimum inhibitory concentration (MIC) assays. Toxicity was evaluated by testing Artemia nauplii mortality assays. Results: Methanolic and aqueous extracts prepared from Eucalyptus major and Melaleuca alternifolia leaves displayed noteworthy growth inhibitory activity against all of the bacteria tested, including against methicillin resistant Staphylococcus aureus MRSA and extended spectrum ß-lactamase (ESBL) strains of E. coli and K. pneumoniae. The methanolic E. major leaf extract had particularly good antibacterial activity (MICs=39-625 µg/mL) against all bacterial strains. Notably, this extract had similar potency against an ESBL strain of E. coli as against the corresponding antibiotic-sensitive strain (MICs=78 µg/mL against each) and was significantly more potent against an ESBL K. pneumoniae strain (MIC=39 µg/mL) than against the corresponding antibiotic sensitive strain (MIC=78 µg/mL). All extracts were non-toxic in the Artemia nauplii lethality assay (ALA), indicating their safety for topical use. Conclusion: The potency of the E. major and M. alternifolia extracts against multi-antibiotic resistant bacteria and their lack of toxicity highlight these species as potential targets for antibiotic drug development. Further phytochemical and mechanistic studies of these species are warranted. [ABSTRACT FROM AUTHOR]

Background: Nigella damascena L. (ND) seeds have been incorporated into traditional plant-based medicinal systems for millennia. However, there are conflicting reports on the antibacterial activities of the seed extracts, although phytochemicals known to possess antibacterial activity have been found in the seeds of this species. The toxicities of the extracts have not been studied previously. Aim: This work assesses the ability for aqueous and methanolic ND seed extracts to inhibit the growth of a panel of skin pathogens on agar and in broth, including methicillin-resistant Staphylococcus aureus (MRSA). Qualitative determinations of the phytochemical constituents of the extracts were performed, as well as their toxicity levels. Materials and Methods: Bacterial growth inhibition was evaluated using agar disc diffusion and liquid broth microdilution assays, whilst Artemia nauplii bioassays were used to screen toxicities. Qualitative phytochemical assays were conducted to assess the relative abundance of several important phytochemical compound classes. Results: No inhibition was observed on agar for either the aqueous or methanolic extracts against S. aureus, MRSA, S. epidermidis or S. pyogenes. This was concordant with the liquid microdilution broth assays, with the exception of the methanolic ND extract against S. pyogenes, which produced a minimum inhibitory concentration value of 481 µg/mL. Phenols, saponins, tannins and alkaloid were present in both extract types, while flavonoids could be detected in the methanolic extract only. Both extracts were deemed to be nontoxic in the Artemia nauplii assay. Conclusion: The ND methanolic extract possessed activity against S. pyogenes in liquid broth, but not on agar. The presence of flavonoids in this extract may be responsible for this activity. The extracts were inactive against S. aureus, MRSA and S. epidermidis in agar and broth assays, and were also nontoxic as adjudged by the Artemia nauplii brine shrimp assays. [ABSTRACT FROM AUTHOR]

Introduction: An increase in antibiotic resistance and a corresponding decrease in antimicrobial discovery have directed researchers towards alternative therapies, including plant-based medicines. However, synergistic combinations of plant extracts with conventional antibiotics may be a far more effective approach in overcoming resistance and potentiating the activity of antibiotics that are otherwise ineffective against resistant bacterial strains. Materials and Methods: The antibacterial activity of Taraxacum officinale (L.) Weber ex F.H. Wigg. root extracts was investigated by disc diffusion and quantified by liquid dilution and solid phase MIC assays against some bacterial triggers of autoimmune inflammatory diseases. The extracts were also combined with a range of conventional antibiotics and tested against various bacterial pathogens. The SFIC values obtained from these assays were used to determine the class of combinational effects. Toxicity was evaluated by Artemia nauplii mortality and HDF cytotoxicity assays. Results: Methanolic and ethyl acetate T. officinale root extracts showed good inhibitory activity against several microbial triggers of autoimmune inflammatory diseases, including P. mirabilis, P. vulgaris and A. baylyi. Of further interest, some combinations of the T. officinale root extracts and conventional antibiotics potentiated bacterial growth inhibition compared to the individual components alone. Six synergistic and seven additive interactions were noted. Additionally, two antagonistic interactions were evident, indicating that those combinations should be avoided. All extracts were nontoxic in the ALA and HDF assays, verifying their safety for therapeutic usage. Conclusion: Taraxacum officinale root extracts have potential as inhibitors of bacterial triggers of selected autoimmune inflammatory diseases. Furthermore, extract components may also potentiate the activity of three antibiotics that are relatively ineffective alone. Isolation and identification of these compounds may be beneficial in drug design against several bacteria, including the microbial triggers of rheumatoid arthritis and multiple sclerosis. [ABSTRACT FROM AUTHOR]

Introduction: Nanotechnology is promising for the development of new effective medicines. Silver nanoparticle preparations have been particularly well studied and a range of beneficial effects have been identified. Despite this, the sale of Colloidal silver (CS) preparations for therapeutic purposes has been banned by multiple regulatory authorities (including the FDA and TGA) on the basis of their perceived toxicity. This study evaluates the toxicity of electrolytically produced (CS) preparation, as well as some compounds used to produce CS by chemical synthesis. Materials and Methods: Toxicity of the CS preparation and the chemical toxins were evaluated using the Artemia nauplii toxicity assay. Additionally, the CS was tested for its protective effects against citrate and tannic acid-induced toxicity by screening combinations of CS and the toxins. Results: The CS preparation was nontoxic in the Artemia nauplii bioassay at all concentrations tested and did not induce mortality substantially above the seawater control at all concentrations ≤50 μg/mL. In contrast, citrate and tannic acid were strongly toxic, with LC50 values of 11.6 and 26.8 μg/mL respectively. Interestingly, co-incubation of varying concentrations of the CS preparation with 30 μg/mL of citrate resulted in protection against toxicity, with 50 μg/mL CS inhibiting ~65% of citrate-induced toxicity. In contrast, the CS preparation had no apparent effects on tannic acid-induced toxicity. Conclusion: The CS preparation tested in our study was nontoxic at all concentrations tested. Furthermore, the CS mitigated the toxic effects of citrate, but had no apparent effect on tannic acid-induced toxicity. Further studies are required to verify these findings in other toxicity models and to study the protective molecular mechanisms. [ABSTRACT FROM AUTHOR]

Background: Terminalia ferdinandiana Exell. is an endemic Australian plant with a high anti-oxidant capacity. Liquid solvent extractions of T. ferdinandiana leaves are strong inhibitors of the growth of numerous bacterial pathogens. Despite these promising therapeutic properties, methods for the rapid extraction of large quantities of T. ferdinandiana leaves are lacking. This study aimed to develop a rapid supercritical extraction method to produce extracts which retain therapeutic properties and phytochemistry characteristics. Materials and Methods: Terminalia ferdinandiana leaves were extracted by both solvent maceration extraction and Supercritical fluid extraction (SCE). The extracts were tested for the ability to inhibit bacterial growth using the disc diffusion assay. The antibacterial potency was further quantified using liquid dilution MIC assays. Toxicity was evaluated using an Artemia franciscana nauplii bioassay and GC-MS headspace analysis was used to evaluate phytochemical similarity between the extracts. Results: Terminalia ferdinandiana leaf SCE displayed strong bacterial growth inhibitory activity against bacterial triggers of autoimmune inflammatory diseases, with efficacies similar to the smaller laboratory scale methanolic liquid extractions. The growth inhibition of the ethyl acetate and methanolic solvent extracts and the SCE were particularly noteworthy against P. mirabilis (MICs = 128, 227 and 208μg/mL respectively) and A. baylyi (MICs = 452, 780 and 104 μg/mL respectively). GC-MS analysis of the berry SCE revealed similar terpenoid components and similar abundances to those in methanolic solvent leaf extraction. Furthermore, all liquid extracts and the SCE were non-toxic in the Artemia franciscana toxicity assay. Conclusion: The T. ferdinandiana SCE retained the tested therapeutic properties, was non-toxic and had similar phytochemical profiles as the smaller scale liquid solvent extractions. Thus, SCE is a viable method of rapidly extracting large masses of T. ferdinandiana leaves to produce quality extracts that retain therapeutic properties. [ABSTRACT FROM AUTHOR]

Background: Terminalia ferdinandiana Exell. fruit have been used by the First Australians as a nutritious food and as a medicine for thousands of years. The antibacterial properties of T. ferdinandiana fruit extracts are well reported. However, the therapeutic potential of plants growing in different locations and environmental conditions have not previously been compared. Aim: This study compares the antibacterial efficacy of fruit harvested from two distinct locations in Australia and correlates these activities with their physiochemical properties. Materials and Methods: The growth inhibitory activity of the T. ferdinandiana fruit extracts were evaluated using solid phase disc diffusion and liquid microdilution MIC assays. Artemia nauplii bioassays were used to screen and compare the extracts from both locations. Results: The T. ferdinandiana extracts prepared from fruits sourced from the two distinct regions of Australia inhibited the growth of the panel of bacteria screened, including a highly antibiotic MRSA strain. In general, the methanolic extracts were substantially better inhibitors of bacterial growth than the aqueous extracts, and extracts prepared using the Northern Territory (NT)-derived fruit were substantially more potent than the Western Australian (WA) fruit extracts. MICs substantially <1000 μg/mL were noted for the NT methanolic fruit extract against the reference S. aureus and MRSA bacterial strains respectively. The potency of this extract against the MRSA strain indicates that this extract may function via a distinct mechanism compared to the standard antibiotics tested. Interestingly, the greater antibacterial potency of the NT fruit extracts correlated to high ascorbic acid levels, indicating that the antibacterial mechanism may involve modulation of the redox state. All extracts were nontoxic in the Artemia nauplii toxicity assay, indicating their safety for therapeutic usage. Conclusion: The T. ferdinandiana fruit extracts prepared from both NT and WA each had noteworthy antibacterial activity, although greater activity was noted for the NT fruit extracts. This activity correlated with the antioxidant/ascorbic acid content of the extracts. All extracts were also nontoxic in the Artemia nauplii bioassay, although future studies using mammalian cell lines are required to confirm their safety for therapeutic use. [ABSTRACT FROM AUTHOR]

Introduction: Podocarpus latifolius (Thunb.) R.Br. ex Mirb. is a large tree that is native to southern Africa. This species has been used extensively for multiple therapeutic purposes across the southern part of the African continent. Despite this, P. latifolius leaf extracts have not been rigorously examined growth inhibitory properties against many bacteria, including the bacterial triggers of autoimmune inflammatory diseases. Materials and Methods: The antimicrobial activity of P. latifolia leaf solvent extractions was investigated by disc diffusion and growth time course assays against some bacterial triggers of rheumatoid arthritis and ankylosing spondylitis. The growth inhibitory activity was further quantified by MIC determination. Toxicity was determined using the Artemia franciscana nauplii bioassay. Results: Methanolic and aqueous P. latifolia leaf extracts were good inhibitors of P. mirabilis and K. pneumoniae. The inhibitory activity of both extracts was particularly noteworthy against the bacterial trigger of ankylosing spondylitis (K. pneumonia), with MICs of 343 and 557 µg/mL determined for the methanolic and aqueous extracts respectively. The extracts also displayed noteworthy activity against a bacterial trigger of rheumatoid arthritis (P. mirabilis), with MICs of 580 and 634 µg/mL respectively. The antibacterial activity of the methanolic and aqueous P. latifolia leaf extracts were further investigated by growth time course assays, which showed significant growth inhibition in cultures of P. mirabilis and K. pneumoniae within 1 hr of exposure. The extracts were determined to be nontoxic in the Artemia franciscana nauplii bioassay, indicating their safety for prophylactic use in preventing these autoimmune inflammatory diseases. Conclusion: The lack of toxicity of the P. latifolia leaf extracts and their growth inhibitory bioactivity against the bacterial triggers of rheumatoid arthritis and ankylosing spondylitis indicate their potential in the development of new therapies targeting the onset of these diseases. [ABSTRACT FROM AUTHOR]

Introduction: An increase in antibiotic resistance and a corresponding decrease in antimicrobial discovery have directed researchers towards alternative therapies, including plant-based medicines. However, synergistic combinations of plant extracts with conventional antibiotics may be a far more effective approach in overcoming resistance and potentiating the activity of antibiotics that are otherwise ineffective against resistant bacterial strains. Materials and Methods: The antibacterial activity of Taraxacum officinale (L.) Weber ex F.H. Wigg root extracts was investigated by disc diffusion assays and quantified by liquid dilution and solid phase MIC assays. The extracts were also combined with a range of conventional antibiotics and tested against gastrointestinal disease-causing bacteria. The ΣFIC values obtained from these assays were used to determine the class of combinational effects. Toxicity was evaluated by Artemia nauplii mortality and HDF cytotoxicity assays. Results: Methanolic, aqueous and ethyl acetate T. officinale root extracts showed good inhibitory activity against several gastrointestinal bacterial pathogens. The methanolic were particularly good inhibitors of S. sonneii and S. newport, with MIC values in the range 400-450 μg/mL, whilst the ethyl acetate extract was the most potent inhibitor of S. newport growth (MIC=128 μg/mL). Of further interest, some combinations of the T. officinale root extracts and conventional antibiotics potentiated bacterial growth inhibition compared to the individual components. Five synergistic and two additive interactions were noted. Interestingly, only a single antagonistic interaction was evident, indicating that nearly all combinations could be used without decreasing the antibacterial activity of the components. All extracts were nontoxic in the ALA and HDF assays. Conclusion: Taraxacum officinale root extracts have potential as inhibitors of bacterial gastrointestinal pathogens. Furthermore, extract components may also potentiate the activity of some antibiotics that are relatively ineffective alone. Isolation and identification of these compounds may be beneficial in drug design against several gastrointestinal bacterial pathogens. [ABSTRACT FROM AUTHOR]

The genus Terminalia contains some of the most widely used plants in traditional medicine. Many species possess antifungal, antibacterial, antiviral, antiprotozoal, analgesic, antidiarrheal, antioxidant, antimalarial, anticancer, and anti-inflammatory properties. Some species also have cardiovascular and wound-healing effects. Despite their myriad of traditional uses, relatively few studies have examined the medicinal properties and phytochemistry of most Australian Terminalia spp. The high tannin content of Terminalia spp. has been postulated to be a major contributor to the medicinal properties of this important genus. However, the complexities of tannins are generally believed to make them a poor choice for drug design. Therefore, much of the interest in Terminalia species has been for their nutraceutical and pharmacognostic value, and they remain under-explored in terms of drug discovery. Recent studies have identified many other important phytochemicals within Terminalia species apart from the tannins and have established that these compounds may contribute to their therapeutic bioactivities. Several Australian Terminalia species (particularly Terminalia carpentariae C.T. White, Terminalia catappa L., Terminalia ferdinandiana Exell and Terminalia grandiflora Benth) have received the most attention due to their reported high antioxidant contents. In contrast, other Australian Terminalia spp. have been relatively ignored. This review discusses recent studies into the phytochemistry, medicinal properties and the underlying therapeutic mechanisms of Australian Terminalia species to help direct future areas of research into this important genus. [ABSTRACT FROM AUTHOR]