The discovery of penicillin nearly 90 years ago revolutionized the treatment of bacterial disease. Since that time, numerous other antibiotics have been discovered from bacteria and fungi, or developed by chemical synthesis and have become effective chemotherapeutic options. However, the misuse of antibiotics has lessened the efficacy of many commonly used antibiotics. The emergence of resistant strains of bacteria has seriously limited our ability to treat bacterial illness, and new antibiotics are desperately needed. Since the discovery of penicillin, most antibiotic development has focused on the discovery of new antibiotics derived from microbial sources, or on the synthesis of new compounds using existing antibiotic scaffolds to the detriment of other lines of discovery. Both of these methods have been fruitful. However, for a number of reasons discussed in this review, these strategies are unlikely to provide the same wealth of new antibiotics in the future. Indeed, the number of newly developed antibiotics has decreased dramatically in recent years. Instead, a reexamination of traditional medicines has become more common and has already provided several new antibiotics. Traditional medicine plants are likely to provide further new antibiotics in the future. However, the use of plant extracts or pure natural compounds in combination with conventional antibiotics may hold greater promise for rapidly providing affordable treatment options. Indeed, some combinational antibiotic therapies are already clinically available. This study reviews the recent literature on combinational antibiotic therapies to highlight their potential and to guide future research in this field.

The agricultural industry utilizes antibiotic growth promoters to promote livestock growth and health. However, the World Health Organization has raised concerns over the ongoing spread of antibiotic resistance transmission in the populace, leading to its subsequent ban in several countries, especially in the European Union. These restrictions have translated into an increase in pathogenic outbreaks in the agricultural industry, highlighting the need for an economically viable, non-toxic, and renewable alternative to antibiotics in livestock. Probiotics inhibit pathogen growth, promote a beneficial microbiota, regulate the immune response of its host, enhance feed conversion to nutrients, and form biofilms that block further infection. Commonly used lactic acid bacteria probiotics are vulnerable to the harsh conditions of the upper gastrointestinal system, leading to novel research using spore-forming bacteria from the genus Bacillus. However, the exact mechanisms behind Bacillus probiotics remain unexplored. This review tackles this issue, by reporting antimicrobial compounds produced from Bacillus strains, their proposed mechanisms of action, and any gaps in the mechanism studies of these compounds. Lastly, this paper explores omics approaches to clarify the mechanisms behind Bacillus probiotics.

Medicinal plant use plays an important role in the healthcare of many South Africans. Furthermore, in orthodox medicine, conventional antimicrobial agents are amongst themost commonly prescribed groups of drugs. Therefore, due to the prevalence of use of these two forms of healthcare, there is a high probability for their concurrent use. Thus, the aimof this study was to evaluate the interactive antimicrobial and toxicity profiles of six Southern African medicinal plants (Agathosma betulina, Aloe ferox, Artemisia afra, Lippia javanica, Pelargonium sidoides and Sutherlandia frutescens) when combined with seven conventional antimicrobials (ciprofloxacin, erythromycin, gentamicin, penicillin G, tetracycline, amphotericin B and nystatin). Antimicrobial activity was assessed using the minimum inhibitory concentration (MIC) assay against a range of pathogens and interactions were further classified using the sum of the fractional inhibitory concentration (SFIC). Notable synergistic or antagonistic interactions were studied at various ratios (isobolograms). The toxicity of the individual samples, aswell as the notable combinations, was assessed using the brine-shrimp lethality assay (BSLA) and the 3-(4,5 dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on the HEK-293 human cell line. Of the 420 antimicrobial: plant combinations studied, 14.29% showed synergistic interactions, 7.56% antagonistic, 35.71% additive and 42.44% indifferent interactions. Some notable synergistic interactions (ciprofloxacin with A. betulina and S. frutescens against Escherichia coli) and antagonistic interactions (ciprofloxacin with A. afra organic extract against Escherichia coli) were identified. None of the notable combinations were found to show toxicity in the BSLA or MTT assay. In conclusion, the majority of combinations were found to have no notable interaction, alleviating some concern related to the concurrent use of these two forms of healthcare.No Full Tex