Plant byproducts and waste present enormous environmental challenges and an opportunity for valorization and industrial application. Due to consumer demands for natural compounds, the evident paucity of novel antimicrobial agents against foodborne pathogens, and the urgent need to improve the arsenal against infectious diseases and antimicrobial resistance (AMR), plant byproduct compounds have attracted significant research interest. Emerging research highlighted their promising antimicrobial activity, yet the inhibitory mechanisms remain largely unexplored. Therefore, this review summarizes the overall research on the antimicrobial activity and inhibitory mechanisms of plant byproduct compounds. A total of 315 natural antimicrobials from plant byproducts, totaling 1338 minimum inhibitory concentrations (MIC) (in μg/mL) against a broad spectrum of bacteria, were identified, and a particular emphasis was given to compounds with high or good antimicrobial activity (typically <100 μg/mL MIC). Moreover, the antimicrobial mechanisms, particularly against bacterial pathogens, were discussed in-depth, summarizing the latest research on using natural compounds to combat pathogenic microorganisms and AMR. Furthermore, safety concerns, relevant legislation, consumer perspective, and current gaps in the valorization of plant byproducts-derived compounds were comprehensively discussed. This comprehensive review covering up-to-date information on antimicrobial activity and mechanisms represents a powerful tool for screening and selecting the most promising plant byproduct compounds and sources for developing novel antimicrobial agents.

Inhibitory mechanisms of promising antimicrobials from plant byproducts: A review.

The growing trend of antibiotic-resistant microorganisms and concerns about the use of synthetic antimicrobials are giving rise to new challenges in modern-day society. It is worth noting that an alarming quantity of approximately 1.3 billion tons of food is regrettably wasted on an annual basis due to the detrimental effects of microbial degradation. Plant-derived extracts (PDEs) encompass a diverse array of bioactives, including phytochemicals, crude extracts, and essential oils, that are meticulously extracted from various botanical sources. These PDEs exhibit promising attributes that position them as viable alternatives to conventional antibiotics and preservatives of synthetic origin. This phenomenon can be explained by their innate capacity to hinder the growth of numerous bacteria. The aim of this review is to provide a thorough summary of the existing research on the use of PDEs as natural antibacterial agents. This article provides a summary of their fundamental mechanisms of action as well as an exploration of their practical applications within the food industry. This review encompasses their application in the production of fortified products, their implementation in active food packaging, and the development of innovative encapsulated systems. Research on the antibacterial and in vitro synergistic effects of PDEs has received greater attention recently. The applications of PDEs are limited due to their susceptibility to oxidation and chemical instability, as well as their reduced ability to withstand environmental factors such as oxygen, light, and temperature. However, additional investigations are still necessary to determine and understand the effectiveness of PDEs as natural antimicrobial agents. 

A comprehensive insight into plant-derived extracts/bioactives: Exploring their antimicrobial mechanisms and potential for high-performance food applications

In recent years, antibiotic therapy has encountered significant challenges due to the rapid emergence of multidrug resistance among bacteria responsible for life‐threatening illnesses, creating uncertainty about the future management of infectious diseases. The escalation of antimicrobial resistance in the post‐COVID era compared to the pre‐COVID era has raised global concern. The prevalence of nosocomial‐related infections, especially outbreaks of drug‐resistant strains of Staphylococcus aureus, have been reported worldwide, with India being a notable hotspot for such occurrences. Various virulence factors and mutations characterize nosocomial infections involving S. aureus. The lack of proper alternative treatments leading to increased drug resistance emphasizes the need to investigate and examine recent research to combat future pandemics. In the current genomics era, the application of advanced technologies such as next‐generation sequencing (NGS), machine learning (ML), and quantum computing (QC) for genomic analysis and resistance prediction has significantly increased the pace of diagnosing drug‐resistant pathogens and insights into genetic intricacies. Despite prompt diagnosis, the elimination of drug‐resistant infections remains unattainable in the absence of effective alternative therapies. Researchers are exploring various alternative therapeutic approaches, including phage therapy, antimicrobial peptides, photodynamic therapy, vaccines, host‐directed therapies, and more. The proposed review mainly focuses on the resistance journey of S. aureus over the past decade, detailing its resistance mechanisms, prevalence in the subcontinent, innovations in rapid diagnosis of the drug‐resistant strains, including the applicants of NGS and ML application along with QC, it helps to design alternative novel therapeutics approaches against S. aureus infection.

Emerging strategies and therapeutic innovations for combating drug resistance in Staphylococcus aureus strains: A comprehensive review.

Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires a One Health approach including Antifungal Stewardship (AFS). This study aimed to comprehensively review global studies published on fungal infections and AFR and to recommend solutions to address this growing problem. Materials and Methods: This was a narrative review that was conducted using published papers on fungal infections, AFR, and AFS between January 1961 and March 2024. The literature was searched using PubMed, Google Scholar, Web of Science, and EMBASE. Results: This found that there has been an increase in fungal infections globally, especially among immunocompromised patients. Due to this increase in fungal infections, there has been a proportionate increase in the use of antifungal agents to prevent and treat fungal infections. This increased use of antifungal agents has worsened the problem of AFR contributing to increased morbidity and mortality. Globally, fungal infections have contributed to 150 million infections annually and 1.7 million deaths per year. By the year 2023, over 3.8 million people died from fungal infections. Addressing AFR remains a challenge because the treatment of antifungal-resistant infections is difficult. Finally, the treatment of fungal infections is a global challenge exacerbated by the limited number of antifungal agents to treat invasive fungal infections. Conclusion: The results of this study indicated that fungal infections and AFR are prevalent across humans, animals, agriculture, and the environment. Addressing this problem requires the provision of solutions such as improving the awareness of AFR, conducting further research on the discovery of new antifungal agents, and implementing AFS programs. If this global problem is not addressed, the morbidity and mortality associated with AFR will continue to rise in the future. 

Global Burden of Fungal Infections and Antifungal Resistance from 1961 to 2024: Findings and Future Implications

Shigella infection is a public health problem responsible for approximately 700,000 deaths annually. The management of this disease is impaired by the emergence of multidrug-resistant Shigella species, highlighting the urgent need to search for alternative treatment options. In this regard, investigating medicinal plants traditionally used for the treatment of dysentery, diarrheal infections, and/or associated symptoms in endemic regions might provide an opportunity to identify phytochemicals that could be further used as a basis for the development of future anti-shigella drug candidates. This study was designed to investigate the anti-shigella and antioxidant-based ethnopharmacological potency of some Cameroonian medicinal plants with an emphasis on pharmacokinetic properties of the identified chemical pharmacophore. Briefly, plant species were selected and collected based on their ethnopharmacological uses and information reported in the literature. Crude aqueous, ethanolic, methanolic, and hydroethanolic (30:70, v/v) extracts from these plants were prepared and then screened for their anti-Shigella activity against four Shigella strains and cytotoxicity against Vero and Raw cell lines using microdilution and resazurin-based methods, respectively. The antioxidant activities of potent extracts were evaluated using DPPH, ABTS, NO, and FRAP scavenging assays. The chemical profile of potent extracts was performed using the UHPLC-LIT-MS/MS and the pharmacokinetic properties, druglikeness, and likely molecular targets of the chemical scaffolds identified were predicted using SwissADME and SwissTargetPredictor. Thirty-nine (39) plants belonging to 26 plant families were harvested. Out of the 228 extracts tested, 18 extracts originating from 6 plants (15.38 %) were active (MICs 250–1000 μg/mL) and nontoxic toward Vero (CC50 129.25–684.55 μg/mL) and Raw cell lines (CC50 336.20 to >1000 μg/mL). Six potent extracts from the two plants exhibited moderate to potent DPPH (SC50 8.870–54.410 μg/mL), ABTS (SC50 12.020–27.36 μg/mL), and NO (SC50 0.02–195.85 μg/mL) scavenging activities. Later, these extracts showed interesting ferric iron-reducing power (1.28–12.14 μg equivalent NH2OH/g of extract). The shortest onset of action time (4 and 6 h) observed following inhibition kinetics studies was observed with extracts BFSHE, PMSE, and PMSM. The UHPLC-LIT-MS/MS and some databases (Mass Spectral Library (NIST 14), Human Metabolome Database (HMD), MassBank, SuperNatural 3.0, The Food Database (FooDB), and Chemical Entities of Biological Interest (ChEBI)) allowed the annotation of 18 and 17 metabolites in the extracts from stem bark of P. macrophylla and B. ferruginea respectively. Pharmacokinetic prediction of these chemicals showed that compound 6 (4,6a-bis(Hydroxymethyl)-9a-methyl-3-oxo-1a,1b,3,5,6,6a,7a,9a-octahydrobis (oxireno)[2′,3':5,6; 2″,3'':9,10]cyclodeca[1,2-b]furan-5-yl methacrylate), compound 8 (Corynoxeine), and compounds 35 (Stachybotrydial acetate) demonstrated acceptable druglike and pharmacokinetic properties and might act through inhibition of kinase, transferase, protease, oxidoreductase, and family AG protein-linked receptors. The findings from this investigation demonstrated that Cameroonian medicinal plants are suitable reservoirs of anti-Shigella and antioxidant agents with good drug candidate properties. 

Anti-Shigella and antioxidant-based screening of some Cameroonian medicinal plants, UHPLC-LIT-MS/MS fingerprints, and prediction of pharmacokinetic and drug-likeness properties of identified chemicals.

Antimicrobial resistance (AMR) occurs when microbes no longer respond to any pharmacological agents, rendering the conventional antimicrobial agents ineffective. AMR has been classified as one of the top 10 life-threatening global health problems needed multilevel attention and global cooperation to attain the Sustainable Development Goals (SDGs) according to the World Health Organization (WHO), making the discovery of a new and effective antimicrobial agent a priority. The recommended treatments for drug-resistant microbes are available but limited. Furthermore, the transformation of microbes over time increases the risk of developing drug resistance. Hence, plant metabolites such as terpenes, phenolic compounds and alkaloids are widely studied due to their antibacterial, antiviral, antifungal and antiparasitic effects. Plant-derived antimicrobials are preferred due to their desirable efficacy and safety profile. Plant metabolites work by targeting microbial cell membranes, interfering with the synthesis of microbial DNA/RNA/enzymes and disrupting quorum sensing and efflux pump expression. They also work synergistically with conventional antibiotics to enhance antimicrobial effects. Accordingly, this review aims to identify currently available pharmacological therapies against microbes and AMR, as well as to discuss the importance of plant and secondary metabolites as a possible solution for AMR together with their mechanisms of action. All the information was obtained from government databases, WHO websites, PubMed, Springer, Google Scholar and Science Direct. Based on the information obtained, AMR is regarded as a significant warning to global healthcare. Plant derivatives such as secondary metabolites may be considered as potential therapeutic targets to mitigate the non-ending AMR.

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Review on Plant-Based Management in Combating Antimicrobial Resistance - Mechanistic Perspective

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Review on Plant-Based Management in Combating Antimicrobial Resistance - Mechanistic Perspective