Antibiotic failure has emerged as a critical global health concern, driven by a combination of factors including the stagnation in the discovery of new antibiotics, the widespread emergence of resistance mechanisms among clinical bacterial isolates, and the persistence of recurrent infections caused by tolerant and non-responsive bacterial populations. This review explores contemporary and innovative anti-infective strategies aimed at countering multidrug-resistant (MDR) and persistent bacterial pathogens. Key approaches discussed include the application of antimicrobial peptides, anti-virulence compounds, bacteriophage therapy, and the development of novel therapeutic molecules. Furthermore, this review highlights the strategic repurposing of existing FDA-approved drugs-such as anti-inflammatory, antipsychotic, anti-helminthic, anticancer agents, and statins-as alternative therapeutics. The integration of artificial intelligence in antimicrobial research is also addressed as a promising avenue to accelerate the identification of effective interventions against MDR infections.

Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate (ODHP) was extracted in a previous study from the culture broth of soil isolate Alcaligenes faecalis MT332429 and showed a promising antimycotic activity. This study was aimed to formulate ODHP loaded β-cyclodextrins (CD) nanosponge (NS) hydrogel (HG) to control skin fungal ailments since nanosponges augment the retention of tested agents in the skin. Box-Behnken design was used to produce the optimized NS formulation, where entrapment efficiency percent (EE%), polydispersity index (PDI), and particle size (PS) were assigned as dependent parameters, while the independent process parameters were polyvinyl alcohol % (w/v %), polymer-linker ratio, homogenization time, and speed. The carbopol 940 hydrogel was then created by incorporating the nanosponges. The hydrogel fit Higuchi’s kinetic release model the best, according to in vitro drug release. Stability and photodegradation studies revealed that the NS-HG remained stable under tested conditions. The formulation also showed higher in vitro antifungal activity against Candida albicans compared to the control fluconazole. In vivo study showed that ODHP-NS-HG increased survival rates, wound contraction, and healing of wound gap and inhibited the inflammation process compared to the other control groups. The histopathological examinations and Masson’s trichrome staining showed improved healing and higher records of collagen deposition. Moreover, the permeability of ODHP-NS-HG was higher through rats’ skin by 1.5-folds compared to the control isoconazole 1%. Therefore, based on these results, NS-HG formulation is a potential carrier for enhanced and improved topical delivery of ODHP. Our study is a pioneering research on the development of a formulation for ODHP produced naturally from soil bacteria. Key points: • Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate was successfully formulated as a nanosponge hydrogel and statistically optimized. • The new formula exhibited in vitro good stability, drug release, and higher antifungal activity against C. albicans as compared to the fluconazole. • Ex vivo showed enhanced skin permeability, and in vivo analysis showed high antifungal activity as evidenced by measurement of various biochemical parameters and histopathological examination.

Resistance to antifungal agents represents a major clinical challenge, leading to high morbidity and mortality rates, especially in immunocompromised patients. In this study, we screened soil bacterial isolates for the capability of producing metabolites with antifungal activities via the cross-streak and agar cup-plate methods. One isolate, coded S6, showed observable antifungal activity against Candida (C.) albicans ATCC 10231 and Aspergillus (A.) niger clinical isolate. This strain was identified using a combined approach of phenotypic and molecular techniques as Lysinibacillus sp. MK212927. The purified metabolite displayed fungicidal activity, reserved its activity in a relatively wide range of temperatures (up to 60 °C) and pH values (6–7.8) and was stable in the presence of various enzymes and detergents. As compared to fluconazole, miconazole and Lamisil, the minimum inhibitory concentration of the metabolite that showed 90% inhibition of the growth (MIC₉₀) was equivalent to that of Lamisil, half of miconazole and one fourth of fluconazole. Using different spectroscopic techniques such as FTIR, UV spectroscopy, 1D NMR and 2D NMR techniques, the purified metabolite was identified as terbinafine, an allylamine antifungal agent. It is deemed necessary to note that this is the first report of terbinafine production by Lysinibacillus sp. MK212927, a fast-growing microbial source, with relatively high yield and that is subject to potential optimization for industrial production capabilities.

Fungal infections currently pose a real threat to human lives. In the current study, soil bacterial isolates were screened for the production of antifungal compounds to combat human fungal pathogens. Notably, the bacterial F1 isolate exhibited antimycotic action towards the Candida albicans ATCC 10231 and Aspergillus niger clinical isolates. By employing phenotypic and molecular techniques, we identified the F1 isolate as the Bacillus toyonensis isolate OQ071612. The purified extract showed stability within a pH range of 6–7 and at temperatures of up to 50 °C. It demonstrated potential antifungal activity in the presence of various surfactants, detergents, and enzymes. The purified extract was identified as 6-methoxy-1H-Indole-2-carboxylic acid using advanced spectroscopic techniques. To optimize the antifungal metabolite production, we utilized response surface methodology (RSM) with a face-centered central composite design, considering nutritional and environmental variables. The optimal conditions were as follows: starch (5 g/L), peptone (5 g/L), agitation rate of 150 rpm, pH 6, and 40 °C temperature. A confirmatory experiment validated the accuracy of the optimization process, resulting in an approximately 3.49-fold increase in production. This is the first documented report on the production and characterization of 6-methoxy-1H-Indole-2-carboxylic acid (MICA) antifungal metabolite from Bacillus toyonensis.

Antimicrobial resistance (AMR) and foodborne infections represent significant public health concerns, with food products serving as potential vehicles for the transmission of pathogenic and antimicrobial-resistant microorganisms. In this study, a total of 133 food samples, including vegetables, dairy products, meats, seafood, ready-to-eat foods, and beverages, were collected and analyzed. Microbiological investigation revealed microbial growth in 128 samples, yielding 128 bacterial and fungal microorganisms. Among the identified microorganisms, Escherichia coli (20.3%), Staphylococcus aureus (20.3%), Salmonella spp. (14.8%), and Bacillus cereus (11.7%) were the most prevalent taxa. Fungal isolates accounted for 14.9% of the identified microorganisms and included Penicillium spp., Candida spp., Aspergillus spp., and unidentified yeasts. Microbial identification was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), which achieved species-level identification for 125 microorganisms (97.7%), while three microorganisms (2.3%) yielded low-confidence identifications. Antimicrobial susceptibility testing demonstrated variable resistance patterns among the recovered microorganisms, with higher resistance frequencies generally observed among Gram-negative bacteria. Multidrug-resistant (MDR) phenotypes were detected among several isolates, particularly Escherichia coli and Pseudomonas aeruginosa, with additional MDR patterns observed in Enterobacter cloacae complex and Staphylococcus aureus. This study provides updated region-specific data on the diversity and antimicrobial resistance profiles of foodborne microorganisms recovered from different food categories in Egypt. The findings underscore the importance of continuous surveillance of foodborne pathogens and antimicrobial resistance to support food safety monitoring, risk assessment, and public health interventions.