Molecular Pathogens 2024, Vol.15, No.4, 170-178 http://microbescipublisher.com/index.php/mp 176 human phagocytic cells without affecting host cell viability, suggesting a potential for safe therapeutic use. Additionally, predatory bacteria have been found to be non-toxic and non-immunogenic in human cell lines and animal models, further supporting their safety profile. Importantly, these bacteria have shown efficacy in reducing bacterial burdens in vivo, as evidenced by their ability to protect mice from lethal bacterial challenges and reduce Klebsiella pneumoniae burden in rat lungs. While the current findings are encouraging, several areas require further investigation to fully realize the therapeutic potential of predatory bacteria. Detailed molecular studies are needed to understand the predatory mechanisms and the sequential release of enzymes during the predatory cycle. This knowledge will be crucial for optimizing the use of predatory bacteria as therapeutic agents. Investigating the interactions between predatory bacteria and host immune cells will provide insights into their persistence, immune evasion, and potential immunomodulatory effects. Long-term studies on the genetic stability of predatory bacteria are essential to ensure that they do not acquire pathogenic traits through horizontal gene transfer. Rigorous clinical trials are necessary to evaluate the safety, efficacy, and optimal dosing regimens of predatory bacteria in human subjects. Expanding the range of pathogens tested, including those with different resistance mechanisms, will help establish the broad-spectrum efficacy of predatory bacteria. The potential of predatory bacteria as therapeutic agents represents a novel and promising approach to combating antibiotic-resistant infections. Their unique mode of action, which involves the direct predation and elimination of pathogenic bacteria, offers a complementary strategy to traditional antibiotics. The ability of predatory bacteria to reduce bacterial burdens in vivo without causing significant adverse effects highlights their potential as "living antibiotics". However, the transition from experimental models to clinical application will require comprehensive research to address safety, efficacy, and regulatory challenges. If these hurdles can be overcome, predatory bacteria could become a valuable addition to the arsenal against antibiotic-resistant pathogens, offering hope in the fight against one of the most pressing global health threats of our time. Acknowledgments I would like to express my gratitude to the reviewers for their valuable feedback, which helped improve the manuscript. Conflict of Interest Disclosure The author affirms that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Bukowska-Faniband E., Andersson T., and Lood R., 2020, Studies on Bd0934 and Bd3507, two secreted nucleases fromBdellovibrio bacteriovorus, reveal sequential release of nucleases during the predatory cycle, Journal of Bacteriology, 202(18): 1-14. https://doi.org/10.1128/JB.00150-20 Cavallo F., Jordana L., Friedrich A., Glasner C., and Dijl J., 2021, Bdellovibrio bacteriovorus: a potential ‘living antibiotic’ to control bacterial pathogens, Critical Reviews in Microbiology, 47: 630-646. https://doi.org/10.1080/1040841X.2021.1908956 Duncan M., Gillette R., Maglasang M., Corn E., Tai A., Lazinski D., Shanks R., Kadouri D., and Camilli A., 2019, High-throughput analysis of gene function in the bacterial predator Bdellovibrio bacteriovorus, mBio, 10(3): 1-12. https://doi.org/10.1128/mBio.01040-19 Feng S., Tan C., Constancias F., Kohli G., Cohen Y., and Rice S., 2017, Predation by Bdellovibrio bacteriovorus significantly reduces viability and alters the microbial community composition of activated sludge flocs and granules, FEMS Microbiology Ecology, 93(4): fix020. https://doi.org/10.1093/femsec/fix020 Findlay J., Flick-Smith H., Keyser E., Cooper I., Williamson E., and Oyston P., 2019, Predatory bacteria can protect SKH-1 mice from a lethal plague challenge, Scientific Reports, 9: 7225. https://doi.org/10.1038/s41598-019-43467-1 Gupta S., Tang C., Tran M., and Kadouri D.,2016, Effect of predatory bacteria on human cell lines, PLoS ONE, 11(8): e0161242. https://doi.org/10.1371/journal.pone.0161242 Hetta H., Ramadan Y., Al-Harbi A., Ahmed E., Battah B., Ellah N., Zanetti S., abd Donadu M., 2023, Nanotechnology as a promising approach to combat multidrug resistant bacteria: a comprehensive review and future perspectives, Biomedicines, 11(2): 413. https://doi.org/10.3390/biomedicines11020413
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