Live Bacterial Chemistry in Biomedicine
Background Introduction
The application of live bacteria in the biomedical field has garnered significant attention in recent years. Traditionally, bacteria were viewed as pathogens that needed to be eradicated. However, with the advancement of modern bacteriology, there has been a growing recognition of the complex symbiotic relationship between bacteria and the human body, as well as their unique potential in therapy, diagnosis, and drug delivery. Although chemical engineering offers innovative ideas to enhance biosafety and improve treatment outcomes, the comprehensive application of live bacteria in precision medicine still faces significant challenges. In particular, the fate of live bacteria after entering the human body, the complexity of their biological processes, and the diversity of individualized treatments are pressing issues that need to be addressed. Additionally, the introduction of artificial intelligence (AI) and machine learning (ML) technologies provides new possibilities for designing and predicting the interactions between live bacteria and the human body.
Source of the Paper
The paper, titled “Live Bacterial Chemistry in Biomedicine”, was co-authored by Senfeng Zhao, Qian Chen, Qimanguli Saiding, and others from the Center for Nanomedicine at Brigham and Women’s Hospital, Harvard Medical School. It was published on April 4, 2025, in the journal Chem, with the DOI 10.1016/j.chempr.2025.102436.
Main Content of the Paper
1. Programmability of Live Bacterial Chemistry
The paper first summarizes the programmability of live bacterial chemistry and its applications in biomedicine. The surface structures and chemical compositions of live bacteria are the primary sites for their interaction with the external environment, making them the main targets for chemical engineering modifications. The authors discuss in detail the applications of non-covalent and covalent interactions in live bacterial surface chemistry, including electrostatic interactions, hydrogen bonding, and hydrophobic interactions. While these methods are simple and flexible, they lack specificity. In contrast, covalent interactions (such as NHS ester coupling reactions and imidoester reactions) offer higher stability and selectivity, albeit requiring more complex reaction conditions.
2. Live Bacterial Gene Chemistry
Advances in genetic engineering have opened new avenues for the application of live bacteria in biomedicine. The paper introduces biological and physical gene engineering methods, such as the CRISPR-Cas system, transcription activator-like effector nucleases (TALENs), and zinc-finger nucleases (ZFNs). Additionally, chemical methods like base editing and epigenetic modifications provide new perspectives for gene programming. Base editing technology enables precise modification of genetic information through chemical conversion of base pairs, while epigenetic modifications alter gene expression patterns through methylation and phosphorothioate modifications.
3. Other Chemical Modifications of Live Bacteria
Beyond surface and gene chemistry, the paper also discusses intracellular gelation-mediated “cyborg bacteria.” By introducing small molecules or polymer monomers into the bacterial cytoplasm and forming a hydrogel matrix within the cells, the physical rigidity of bacteria can be enhanced, inhibiting their division ability and thereby reducing safety risks in vivo. These “cyborg” bacteria retain the ability to secrete functional metabolites, offering new possibilities for biomedical applications.
4. Application of AI and Machine Learning
The paper highlights that AI and ML technologies have the potential to revolutionize the design of chemically engineered bacteria and provide substantial progress in the development of live bacterial therapies. By analyzing large datasets of bacterial proteins, gene sequences, and more, AI and ML can more reasonably predict new chemical modification strategies and improve the accuracy and efficiency of modifications. Furthermore, AI frameworks can help analyze patient-specific data, intelligently customizing the functions and behaviors of live bacteria for personalized precision medicine.
5. Applications of Live Bacteria in Biomedicine
The paper summarizes the physical, chemical, and biological properties endowed by chemical engineering modifications to live bacteria and their main applications in cancer therapy, oral disease treatment, tissue regeneration, intestinal disease treatment, brain disease treatment, antibacterial applications, inflammatory disease treatment, disease diagnosis, kidney disease treatment, and acute and chronic poisoning. For example, by modifying nanomaterials onto the surface of live bacteria, biohybrid systems responsive to external physical stimuli can be constructed, enabling in vivo control of biomedical functions. Additionally, chemical modifications can enhance the intestinal colonization ability of live bacteria, improving treatment efficacy.
Significance and Value of the Paper
This paper systematically summarizes the latest advancements in live bacterial chemistry and its applications in biomedicine, providing important theoretical support and technical guidance for the future clinical transformation of live bacterial therapies. Through chemical engineering modifications, live bacteria can not only enhance their biomedical functions but also improve their safety and stability in vivo. Moreover, the introduction of AI and ML technologies offers new possibilities for personalized treatments using live bacteria. Although the application of live bacteria in biomedicine still faces numerous challenges, its prospects are undoubtedly bright, paving the way for innovative therapeutic approaches in the future.
Highlights Summary
- Programmability: The paper details the programmability of live bacterial surface and gene chemistry, offering new insights into the biomedical applications of non-covalent and covalent interactions.
- Gene Editing: The introduction of base editing and epigenetic modification technologies provides precise tools for live bacterial gene programming.
- Cyborg Bacteria: Intracellular gelation-mediated “cyborg bacteria” offer new solutions for the safety and functionality of live bacteria.
- AI and ML Applications: The use of AI and ML technologies enables personalized treatments and precision medicine with live bacteria.
- Broad Application Prospects: Chemically engineered live bacteria demonstrate immense potential in various fields, including cancer therapy and intestinal disease treatment.
This paper not only provides comprehensive theoretical support for the application of live bacteria in biomedicine but also points the way for future research and clinical transformation.