Engineering the gut microbiome

Bai, Xuekun; Huang, Ziyu; Duraj-Thatte, Anna; Ebert, Matthias; Lau, Raphaela Iris; Burgermeister, Elke; Xue, Le; Scott, Benjamin M. T.; Li, Guoxin; Zuo, Tao

doi:10.1038/s44222-023-00072-2

Cited by 13 publications

(7 citation statements)

References 189 publications

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“…Therefore, exploiting coatings capable of responding to various pathological microenvironments in vivo is highly desirable for developing intelligent surfacefunctionalized bacterial bioagents. Finally, given that bacteria have been linked to metabolic, autoimmune, and infectious diseases, 16 functionalized bacteria can be broadly explored for application in treating diverse diseases. Of note, the pathogenesis of diverse diseases and the role of bacteria in these diseases need to be further clarified to accurately determine what cargoes are superior for corresponding surface functionalization.…”

Section: Discussionmentioning

confidence: 99%

“…Although optical and photoacoustic imaging techniques have been used to assess the dynamic distribution of administered bacteria, ,, the development of more sensitive methods to count the real-time number of bacteria in target sites is necessary. Third, in comparison to genetic engineering that enables bacteria to produce therapeutic molecules in a controlled manner, , the shedding of codeposited cargoes mainly depends on bacterial reproduction. Therefore, exploiting coatings capable of responding to various pathological microenvironments in vivo is highly desirable for developing intelligent surface-functionalized bacterial bioagents.…”

Section: Discussionmentioning

confidence: 99%

“…The early prevailing paradigm for developing bacterial therapeutics focuses on the use of genetic attenuations to improve safety, while attenuated strains often show limited therapeutic efficacy, particularly in cancer patients. , Moving forward, the methods capable of integrating inherent properties of bacteria with a variety of functional payloads provide an opportunity to improve the efficacy of bacterial therapeutics . Despite these achievements, genetic engineering and synthetic biology tools can manipulate only comparatively few strains, such as Escherichia coli and Lactobacillus , and there are no versatile tools currently available for modifying different strains …”

Section: Introductionmentioning

confidence: 99%

“…15 Despite these achievements, genetic engineering and synthetic biology tools can manipulate only comparatively few strains, such as Escherichia coli and Lactobacillus, and there are no versatile tools currently available for modifying different strains. 16 Recent breakthroughs in the surface modification of bacteria have opened a new chapter in functionalizing bacteria via chemical methods. Since cornerstone work in 2007, 17 polydopamine has been discovered to be a highly adaptable surface functionalization strategy for a wide range of inorganic and organic materials.…”

Section: Introductionmentioning

confidence: 99%

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Dopamine Polymerization-Mediated Surface Functionalization toward Advanced Bacterial Therapeutics

Wang,

Liu

2024

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: Bacteria-based therapy has spotlighted an unprecedented potential in treating a range of diseases, given that bacteria can be used as both drug vehicles and therapeutic agents. However, the use of bacteria for disease treatment often suffers from unsatisfactory outcomes, due largely to their suboptimal bioavailability, dose-dependent toxicity, and low targeting colonization.In the past few years, substantial efforts have been devoted to tackling these difficulties, among which methods capable of integrating bacteria with multiple functions have been extensively pursued. Different from conventional genetic engineering and modern synthetic bioengineering, surface modification of bacteria has emerged as a simple yet flexible strategy to introduce different functional motifs. Polydopamine, which can be easily formed via in situ dopamine oxidation and self-polymerization, is an appealing biomimetic polymer that has been widely applied for interfacial modification and functionalization. By virtue of its catechol groups, polydopamine can be efficiently codeposited with a multitude of functional elements on diverse surfaces.In this Account, we summarize the recent advances from our group with a focus on the interfacial polymerization-mediated functionalization of bacteria for advanced microbial therapy. First, we present the optimized strategy for bacterial surface modification under cytocompatible conditions by in situ dopamine polymerization. Taking advantage of the hydrogen bonding, π−π stacking, Michael addition, and Schiff base reaction with polydopamine, diverse functional small molecules and macromolecules are facilely codeposited onto the bacterial surface. Namely, monomodal, dual-modal, and multimodal surface modification of bacteria can be achieved by dopamine self-deposition, codeposition with a unitary composition, and codeposition with a set of multiple components, respectively. Second, we outline the regulation of bacterial functions by surface modification. The formed polydopamine surface endows bacteria with the ability to resist in vivo insults, such as gastrointestinal tract stressors and immune clearance, resulting in greatly improved bioavailability. Integration with specific ligands or therapeutic components enables the modified bacteria to increase targeting accumulation and colonization at lesion sites or play synergistic effects in disease treatment. Bacteria codeposited with different bioactive moieties, such as protein antigens, antibodies, and immunoadjuvants, are even able to actively interact with the host, particularly to elicit immune responses by either suppressing immune overactivation to promote the reversion of pathological inflammations or provoking protective innate and/or adaptive immunity to inhibit pathogenic invaders. Third, we highlight the applications of surface-modified bacteria as multifunctional living therapeutics in disease treatment, especially alleviating inflammatory bowel diseases via oral delivery and intervening in di...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dopamine Polymerization-Mediated Surface Functionalization toward Advanced Bacterial Therapeutics

Wang,

Liu

2024

Acc. Chem. Res.

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“…The microbiota has a profound impact on human health and these communities are implicated in many pathological states. This impact has created growing interest in methods that can manipulate the human host-microbiota system to combat disease( 1 – 4 ). One approach is to use engineering biology techniques to construct engineered live biotherapeutic products (eLBPs)( 5 ).…”

Section: Introductionmentioning

confidence: 99%

An antimicrobial peptide expression platform for targeting pathogenic bacterial species

Rutter,

Dekker,

Clare

et al. 2023

Preprint

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Bacteriocins are antimicrobial peptides that are naturally produced by many bacteria. They hold great potential in the fight against antibiotic resistant bacteria, including ESKAPE pathogens. However, they often have low stabilityin vivoand therefore, may not be effective when administered orally. Engineered live biotherapeutic products (eLBPs) that secrete bacteriocins can be created to deliver bacteriocins directly at the site of infection. Here we develop a modular bacteriocin secretion platform that can be used to express and secrete multiple bacteriocins from non-pathogenicEscherichia colihost strains. As a proof of concept we create Enterocin A and Enterocin B secreting strains that show strong antimicrobial activity againstEnterococcus faecalisandEnterococcus faecium, and characterise this activity in both solid culture and liquid co-culture. We then develop a Lokta-Volterra model that can be used to capture the interactions of these competitor strains. We show that simultaneous exposure to EntA and EntB can increase the level ofEnterococcuskilling and delay the development of resistance. Our system has the potential to be used as an eLBP to secrete additional bacteriocins for the targeted killing of other pathogenic bacteria.

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Recent advances on emerging nanomaterials for diagnosis and treatment of inflammatory bowel disease

Fu,

Xu,

Chen

et al. 2023

Journal of Controlled Release

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Engineering the gut microbiome

Cited by 13 publications

References 189 publications

Dopamine Polymerization-Mediated Surface Functionalization toward Advanced Bacterial Therapeutics

Dopamine Polymerization-Mediated Surface Functionalization toward Advanced Bacterial Therapeutics

An antimicrobial peptide expression platform for targeting pathogenic bacterial species

Recent advances on emerging nanomaterials for diagnosis and treatment of inflammatory bowel disease

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