Proof-of-Concept Preclinical Use of <i>Drosophila melanogaster</i> in the Initial Screening of Immunomodulators

Drug discovery is a complex process, and the use of a comprehensive approach is deemed necessary to discover new chemical entities with novel mechanisms of action. This research was carried out to determine whether Drosophila melanogaster can serve as an appropriate model organism in the initial screening of drug candidates with immunomodulatory activities. To test this, we performed phenotypic assay and molecular analysis to investigate the immunomodulatory activities of aspirin, dexamethasone, curcumin, and epigallocatechin gallate (EGCG), that have been reported to yield such effects in the mammalian model system. In vivo survival analysis demonstrated that all drugs/compounds were relatively safe at the tested concentrations. In the infection assay, curcumin and EGCG showed a protective signature to bacterial infection in flies lacking Toll-mediated immune responses. Furthermore, dexamethasone and aspirin, drugs with immunosuppressive activity, could improve the survival of PGRP-LBΔ mutant flies with hyperactivated immune system. These phenotypes were supported by RT-qPCR-based molecular analysis, revealing that drugs/compounds used in this study could modulate the expression level of genes related to the immune system. In conclusion, while curcumin and EGCG could promote the improvement of fly survival against infection, aspirin and dexamethasone were able to suppress overactivation of immune responses in D. melanogaster. These results are in line with the ones observed in the mammalian model system, further emphasizing the notion that flies would serve as a prospective model organism in the initial screening of drug candidates for their immunomodulatory activities prior to further checking in the mammalian animal models. In the end, this will reduce the use of mammalian animal models for preliminary experiments in an effort to discover/repurpose drugs with immunomodulatory activity

Pharmaceutical approaches on antimicrobial resistance: prospects and challenges

The rapid increase in pathogenic microorganisms with antimicrobial resistant profiles has become a significant public health problem globally. The management of this issue using conventional antimicrobial preparations frequently results in an increase in pathogen resistance and a shortage of effective antimicrobials for future use against the same pathogens. In this review, we discuss the emergence of AMR and argue for the importance of addressing this issue by discovering novel synthetic or naturally occurring antibacterial compounds and providing insights into the application of various drug delivery approaches, delivered through numerous routes, in comparison with conventional delivery systems. In addition, we discuss the effectiveness of these delivery systems in different types of infectious diseases associated with antimicrobial resistance. Finally, future considerations in the development of highly effective antimicrobial delivery systems to combat antimicrobial resistance are presented

Progress and Challenges in Antimicrobial Resistance and Bacterial Vaccines

In recent decades, pathogens have continued to strike humans in the form of newly emerging or re-emerging infectious diseases, opportunistic infectious diseases, and infections caused by drug-resistant microbes. In response, humans have developed modern platform technologies that can produce effective vaccines to prevent pathogens from causing infectious diseases. Vaccines against antimicrobial-resistant organisms could prevent or minimize life-threatening infections, thus lowering healthcare costs. These pharmaceutical products could also reduce antibiotic use, lowering the risk of antimicrobial resistance (AMR) emergence. Furthermore, once a population has received enough vaccines, indirect protection via herd immunity can help to prevent the spread of resistant strains. In this sense, antibiotics would be unnecessary once the burden of pathogen-associated illnesses is reduced. Based on such a notion, bacterial vaccines would be an excellent and applicable solution to fight AMR. In this review, we highlight our current understanding of AMR, the role of bacterial vaccines in preventing AMR, and discuss the potential of bacterial vaccines and their pitfalls in managing infectious diseases