Molecular Pathogens 2024, Vol.15, No.4, 170-178 http://microbescipublisher.com/index.php/mp 174 4.2.2 In vivo studies: animal models demonstrating pathogen clearance In vivo studies have provided promising results regarding the safety and efficacy of predatory bacteria. For example, the intravenous administration of Bdellovibrio bacteriovorus in rats demonstrated that these bacteria are non-toxic and do not cause adverse histopathological effects. Although an initial increase in pro-inflammatory cytokines was observed, levels returned to baseline within 18 hours, indicating a transient immune response (Shatzkes et al., 2017). However, while predatory bacteria were able to reduce bacterial burden in the lungs, they were less effective in systemic infections, such as those caused byKlebsiella pneumoniae in the bloodstream. 4.3 Therapeutic applications and clinical potential 4.3.1 Potential use in human infectious diseases The potential use of predatory bacteria in treating human infectious diseases is gaining traction. Studies have shown that these bacteria are non-pathogenic to human cells and can effectively target and kill multidrug-resistant pathogens (Gupta et al., 2016; Mitchell et al., 2020). This positions predatory bacteria as a promising alternative or adjunct to traditional antibiotics, especially in cases where conventional treatments fail due to resistance. 4.3.2 Applications in biofilm-related infections Biofilm-related infections pose a significant challenge due to their resistance to antibiotics. Predatory bacteria have shown potential in disrupting biofilms and reducing bacterial load within these structures. By penetrating and consuming the bacteria within biofilms, predatory bacteria could offer a novel approach to treating these persistent infections (Madhusoodanan, 2019). 4.4 Synergistic effects with traditional antibiotics Combining predatory bacteria with traditional antibiotics could enhance the overall effectiveness of treatment. This synergistic approach may help in reducing bacterial resistance and improving patient outcomes. Studies suggest that while predatory bacteria alone are effective, their combination with antibiotics could provide a more comprehensive strategy to combat multidrug-resistant infections (Tyson and Sockett, 2017; Liu et al., 2024). 5 Challenges and Limitations 5.1 Resistance development by prey organisms One of the primary concerns with the use of predatory bacteria as a therapeutic tool is the potential for prey organisms to develop resistance. Although predatory bacteria like Bdellovibrio bacteriovorus have co-evolved with their prey, making it difficult for pathogens to resist through simple mutations, the possibility of resistance development cannot be entirely ruled out. Predatory bacteria encode diverse predatory enzymes that are hard for pathogens to resist by simple mutation (Negus et al., 2017). However, the rapid appearance of mutations that confer resistance to other antibacterial agents, such as colicins, suggests that similar mechanisms could potentially arise against predatory bacteria (Upatissa et al., 2023). Therefore, continuous monitoring and research are essential to understand and mitigate the risk of resistance development. 5.2 Environmental factors affecting predatory efficacy The efficacy of predatory bacteria can be significantly influenced by environmental factors. For instance, the presence of certain nutrients, pH levels, and temperature can affect the predatory activity of Bdellovibrio bacteriovorus. Studies have shown that predatory bacteria are effective in vitro, but their performance in vivo can vary due to the complex interactions within a host's body (Shatzkes et al., 2016). Mathematical models have been used to predict the dynamics of predator-prey systems under various environmental conditions, highlighting the importance of understanding these factors to optimize the use of predatory bacteria. Therefore, further research is needed to identify and control environmental variables that could impact the effectiveness of predatory bacteria in different settings. 5.3 Regulatory and safety concerns for clinical applications The introduction of live predatory bacteria as a therapeutic agent raises several regulatory and safety concerns. Although studies have demonstrated that predatory bacteria are non-toxic and non-immunogenic in rodent models
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