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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]

Terminalia canescens DC. Radlk. (family: Combretaceae) is native to northern Australia. Species of the genus Terminalia are widely used as traditional medicines to treat diverse ailments, including bacterial infections. However, we were unable to find any studies that had examined the antimicrobial activity of T. canescens. In this study, T. canescens was screened against a panel of bacterial pathogens, including multi-antibiotic-resistant strains. Solvents with different polarities were used to extract different complements of phytochemicals from T. canescens leaves. Methanolic and aqueous extracts exhibited substantial antimicrobial activity against various pathogens, including those that are multidrug-resistant strains. When combined with some selected clinical antibiotics, some extracts potentiated the antibacterial inhibitory activity. This study identified two synergistic, eleven additive, eleven non-interactive and eight antagonistic interactions. The toxicities of the plant extracts were examined in the Artemia franciscana nauplii assay and were found to be non-toxic, except the aqueous extract, which showed toxicity. Metabolomic liquid chromatography–mass spectrometry (LC-MS) analyses highlighted and identified several flavonoids, including vitexin, quercetin, orientin and kaempferol, as well as the tannins ellagic acid and pyrogallol, which may contribute to the antibacterial activities observed herein. The possible mechanism of action of these extracts was further explored in this study. [ABSTRACT FROM AUTHOR]

Terminalia ferdinandiana Exell, Terminalia grandiflora Benth., Terminalia microcarpa Decne., and Terminalia muelleri Benth. (family: Combretaceae) belong to the genus Terminalia. Plants of this genus have been extensively used as traditional medicines to treat a variety of illnesses, including pathogen infections. However, we were unable to find any studies that have investigated the antibacterial activity of T. microcarpa. Similarly, whilst some preliminary studies have examined the antimicrobial properties of T. muelleri and T. grandiflora, they did not test the extracts against antibiotic-resistant pathogens. This study screens the antimicrobial activity of T. grandiflora, T. microcarpa, and T. muelleri and compares it to that of T. ferdinandiana extracts prepared from both the fruit and leaves against a range of pathogens, including multi-antibiotic-resistant strains. Solvents with varying polarities were used to extract different phytochemical constituents from the leaves of T. grandiflora, T. microcarpa, and T. muelleri and from the fruit and leaves of T. ferdinandiana. The aqueous and methanolic extracts each displayed significant antimicrobial activity when tested against the bacterial pathogens, including against the multidrug-resistant strains. When these extracts were tested in combination with selected antibiotics, some extracts potentiated the antimicrobial activity. This study identifies twelve synergistic, fifty-eight additive, and sixty non-interactive combinations, as well as thirty antagonistic effects. The extracts were evaluated for toxicity using the Artemia franciscana nauplii lethality assay (ALA) and were each classified as non-toxic, with the exception of the methanolic and aqueous T. ferdinandiana fruit extracts and the aqueous and ethyl acetate T. ferdinandiana leaf extracts. Metabolomic analysis using liquid chromatography–mass spectrometry (LC-MS) highlighted several flavonoids and tannins that may contribute to the antimicrobial activities reported herein. The potential antibacterial mechanism(s) of the T. ferdinandiana extracts are discussed in this study. [ABSTRACT FROM AUTHOR]

Terminalia petiolaris A. Cunn. Ex Benth. (genus: Terminalia, family: Combretaceae) is native to Australia. Terminalia spp. have traditionally been used to treat various ailments, including bacterial infections. Solvents of varying polarity were used to extract compounds from leaves of this species, and the extracts were tested against a panel of bacteria, including antibiotic-resistant strains. The methanolic and water extracts showed substantial inhibitory activity against several bacteria, including antibiotic-resistant strains in both disc diffusion and liquid dilution assays. Combining these extracts with selected conventional antibiotics enhanced the inhibition of bacterial growth for some combinations, while others showed no significant interaction. In total, two synergistic, twenty-five additive, twenty-three non-interactive and one antagonistic interaction were observed. The methanolic and ethyl acetate plant extracts were found to be non-toxic in Artemia franciscana nauplii toxicity assays. A liquid chromatography–mass spectrometry metabolomics analysis identified several flavonoid compounds, including miquelianin, trifolin and orientin, which might contribute to the observed activities. The potential modes of these active extracts are further discussed in this study. [ABSTRACT FROM AUTHOR]

The genus Eremophila (family Scrophulariaceae) consists of approximately 200 species that are widely distributed in the semi-arid and arid regions of Australia. Multiple Eremophila spp. are used as traditional medicines by the First Australians in the areas in which they grow. They are used for their antibacterial, antifungal, antiviral, antioxidant, anti-diabetic, anti-inflammatory, and cardiac properties. Many species of this genus are beneficial against several diseases and ailments. The antibacterial properties of the genus have been relatively well studied, with several important compounds identified and their mechanisms studied. In particular, Eremophila spp. are rich in terpenoids, and the antimicrobial bioactivities of many of these compounds have already been confirmed. The therapeutic properties of Eremophila spp. preparations and purified compounds have received substantially less attention, and much study is required to validate the traditional uses and to highlight species that warrant further investigation as drug leads. The aim of this study is to review and summarise the research into the medicinal properties, therapeutic mechanisms, and phytochemistry of Eremophila spp., with the aim of focussing future studies into the therapeutic potential of this important genus. [ABSTRACT FROM AUTHOR]