• Smart Probiotic-NanoAntibiotic Systems: Innovative Strategies for Combating Multidrug-Resistant Pathogens
  • Shiva Ahmadi Pour Sereshkeh,1 Ali Mohammadi,2,*
    1. IraPh.D. student of Microbiology, Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran.n
    2. Associate Professor of Microbiology, Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran.


  • Introduction: Antimicrobial resistance (AMR) has become an alarming global health crisis, undermining the efficacy of conventional antibiotics and complicating the treatment of infectious diseases. Multidrug-resistant (MDR) pathogens have developed sophisticated mechanisms to evade antimicrobial agents, leading to increased morbidity, mortality, and healthcare costs. Traditional antimicrobial therapies often lack specificity, inadvertently disrupting beneficial microbiota and contributing to further resistance. Novel approaches are urgently needed to enhance treatment precision and efficacy. Recent advances in nanotechnology and genetic engineering, particularly CRISPR-Cas systems, offer promising solutions. Engineered probiotic bacteria loaded with nanocarriers constitute an innovative strategy—using live bacteria as delivery vehicles for targeted nanoantibiotics, aiming to identify and eradicate resistant bacteria precisely within the host. This integrated approach could revolutionize infection management by improving specificity, reducing side effects, and limiting resistance development.
  • Methods: This review analyzed over 50 peer-reviewed articles published from 2018 to 2024, focusing on engineered probiotic systems, nanoantibiotics, and CRISPR-based detection. Data from experimental and preclinical studies were examined, emphasizing detection accuracy, delivery efficiency, stability, safety profiles, and technological innovations. Particular interest was given to studies integrating nanocarriers with gene-editing tools to achieve targeted antimicrobial action.
  • Results: The reviewed literature highlights that genetically engineered probiotics equipped with CRISPR-Cas components can identify resistant bacteria with success rates exceeding 95%. These systems detect pathogen-specific genetic markers rapidly and accurately, facilitating targeted drug delivery. Nanoantibiotics encapsulated within nanocarriers are subsequently released in a controlled manner, precisely at infection sites. Such targeted delivery significantly reduces bacterial load while preserving beneficial microbiota, thereby minimizing side effects and off-target impacts. Preclinical studies demonstrate promising efficacy in laboratory conditions, including enhanced bacterial clearance and resistance suppression. However, several challenges remain—such as maintaining probiotic viability within the host, ensuring long-term safety of nanocarriers, and achieving scalable production. Overcoming these issues through ongoing technological innovation is essential for future clinical translation.
  • Conclusion: Emerging smart probiotic-nanoantibiotic systems hold transformative potential for combating MDR pathogens. Their ability to swiftly detect, specifically target, and eradicate resistant bacteria could markedly improve infection outcomes while minimizing collateral damage to the host’s microbiome. Although significant progress has been made, further research is necessary to optimize system stability, ensure safe long-term application, and meet regulatory standards. Addressing these hurdles will facilitate clinical adoption and provide an effective tool against the escalating threat of antimicrobial resistance. The integration of nanotechnology and gene editing presents an exciting frontier, promising more personalized, precise, and sustainable antimicrobial therapies. Continued multidisciplinary efforts and rigorous validation are crucial to realizing the full potential of these innovative platforms and tackling the global antimicrobial resistance crisis effectively.
  • Keywords: Engineered probiotics, nanoantibiotics, multidrug-resistant pathogens, CRISPR-Cas, targeted drug des