Molecular Pathogens 2024, Vol.15, No.2, 50-60 http://microbescipublisher.com/index.php/mp 56 used in agriculture, medicine, and industrial applications, demonstrating their versatility and effectiveness in responding to environmental stimuli (Figure 3) (Angles et al., 2022). Additionally, insect symbionts have been identified as valuable sources of biotechnological applications, including the control of agricultural pests and vectors of human diseases. The manipulation of these symbionts or their associations with hosts can lead to innovative solutions for pest and disease management (Berasategui et al., 2015). Figure 3 MBSs for clinical applications (Adopted from Angles et al., 2022) Image capton: (A, B) MBSs can be used to deliver a range of bio-compounds to different organs and tissues for diverse bacterial therapies. (C) The intestinal lumen is an attractive target for the delivery of non-replicative attenuated bacteria as vaccines (left-most panel, bio compounds (middle panel) and to test for the presence of diseases using available biomarkers (right-most panel). (D) Strategies used to treat tumorigenic tissues with MBSs, including the delivery of RNAs, drugs, and immune stimulants. MBBs are used for targeted delivery of shRNAs and siRNAs to tumors as a mean to knock down drug-resistance genes (top panel); MBBs can also be used as a direct biomanufacturing machinery for synthesis of antitumorigenic compounds (middle panel) or even for the delivery of agonists that will induce the development of an immunity response against the tumor (lower panel). (E) Timeline for major medical applications (Adopted from Angles et al., 2022) Angles et al. (2022) found that microbial-based systems (MBSs) offer significant potential for clinical applications by delivering various bio-compounds to targeted organs and tissues. These systems can be utilized to protect tissue-specific microbiota, inhibit tumor growth, combat pathogenic microorganisms, and deliver safe bacterial vaccines, therapeutics, and nutraceuticals. Specifically, the intestinal lumen is a promising target for the delivery of non-replicative attenuated bacteria as vaccines and biocompounds, as well as for biosensors to detect disease markers. MBSs can treat tumorigenic tissues by delivering RNAs, drugs, and immune stimulants, thus knocking down drug-resistance genes, synthesizing antitumorigenic compounds, and inducing immunity responses against tumors. The development timeline highlights significant milestones, such as the use of auxotrophic probiotics to deliver interleukin 10 in 2003, bacterial vaccine vectors in 2010, attenuated bacterial oral vaccines in 2017, and SimCells for targeted anti-tumor compound delivery in 2020. 7 Future Directions 7.1 Research and development needs The future of microbial predators in disease management hinges on addressing several key research and development needs. One primary area is the comprehensive understanding of microbial predator-prey dynamics within the human microbiome. The reintroduction of bacterial predators to restore gut microbiota diversity, as suggested by Mosca (2016), requires extensive research to identify the specific predators that can thrive and effectively control pathogenic populations without disrupting beneficial microbes. Additionally, the safety and efficacy of predatory bacteria in vivo, as demonstrated in the reduction of Klebsiella pneumoniae burden in rat lungs (Shatzkes et al., 2016), need further validation across different pathogens and host systems. Moreover, the development of novel antimicrobial compounds and biocontrol strategies, as highlighted in Mantravadi et al.
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