Antibiotic Algae by Chemical Surface Engineering

Kerschgens, Isabel P.; Gademann, Karl

doi:10.1002/cbic.201700553

Cited by 19 publications

(19 citation statements)

References 47 publications

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“…It was previously demonstrated that the exposure of the microalgae to high concentration of antibiotic induces the loss of flagella. [60] As growth was not impaired, we hypothesize that loss of flagella function could be the explanation for the reduced phototaxis response of microalgae modified with 0.04 mM of antibiotics in our experiments.…”

Section: Figurementioning

confidence: 80%

“…[58] Additionally, the negatively charged C. reinhardtii cell wall was used for the modification of interacting surfaces by electrostatic interactions. For example, the coating of the microalgae surface was achieved with chitosan, [27] 4-hydroxyproline (4-HP)-rich polypeptides, [59,60] or magnetic microbeads. [61] Covalent attachment of artificial metalloenzymes [57] and antibiotics [62] were recently reported by our group.…”

Section: Figurementioning

confidence: 99%

“…This approach demonstrated high labeling efficacy and prevented the undesired loss of the cargo during its delivery to the target, which was previously observed for biohybrids modified by non-covalent interactions. [27,60] Moreover, our system can still be potentially functionalized with magnetic nanoparticles to extrinsically manipulate the organism by magnetic control. The attachment can be conducted via electrostatic interactions between negatively charged C. reinhardtii cell wall and positively charged magnetic microbeads.…”

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confidence: 99%

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Biohybrid Microswimmers Against Bacterial Infections

Shchelik

Molino

Gademann

2021

Preprint

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Biohybrid microswimmers exploit the natural abilities of motile microorganisms e.g. in releasing cargo on-demand with high spatial and temporal control. However, using such engineered swarms to deliver antibiotics addressing bacterial infections has not yet been realized. In the present study, a design strategy for biohybrid microswimmers is reported, which features the covalent attachment of antibiotics to the motile green algae Chlamydomonas reinhardtii via a photo-cleavable linker. The surface engineering of the algae does not rely on genetic manipulations, proceeds with high efficiency, does not impair the viability or phototactic ability of microalgae, and allows for caging of the antibiotic on the surface for subsequent release via external stimuli. Two different antibiotic classes have been separately utilized, which result in activity against both gram-positive and gram-negative strains. Guiding the biohybrid microswimmers by an external beacon, and on-demand delivery of the drugs by light with high spatial and temporal control, allowed for strong inhibition of bacterial growth in vivo. This efficient strategy could potentially allow for the selective treatment of bacterial infections by engineered algal microrobots with high precision in space and time. Overall, this work presents an operationally simple production of biohybrid microswimmers loaded with antibiotic cargo to combat bacterial infections precisely delivered in three-dimensional space.

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Section: Figurementioning

confidence: 80%

Section: Figurementioning

confidence: 99%

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confidence: 99%

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Biohybrid Microswimmers Against Bacterial Infections

Shchelik

Molino

Gademann

2021

Preprint

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“… 205 This living functionalized algae carrier was chosen as it is biodegradable 206 and does not trigger immune response in mice, 207 and chemical engineering of the surface had been demonstrated previously. 208 The algae were functionalized using the well-established DBCO handle, allowing for copper-free azide–alkyne cycloaddition. Vancomycin was modified at the C-terminus via the installation of a PEG spacer containing the photocleavable o -nitrobenzyl moiety and a terminal azide handle.…”

Section: Recent Developments In Semisynthetic Glycopeptide Antibioticsmentioning

confidence: 99%

Recent Advances in the Development of Semisynthetic Glycopeptide Antibiotics: 2014–2022

2022

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The accelerated appearance of drug-resistant bacteria poses an ever-growing threat to modern medicine’s capacity to fight infectious diseases. Gram-positive species such as methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae continue to contribute significantly to the global burden of antimicrobial resistance. For decades, the treatment of serious Gram-positive infections relied upon the glycopeptide family of antibiotics, typified by vancomycin, as a last line of defense. With the emergence of vancomycin resistance, the semisynthetic glycopeptides telavancin, dalbavancin, and oritavancin were developed. The clinical use of these compounds is somewhat limited due to toxicity concerns and their unusual pharmacokinetics, highlighting the importance of developing next-generation semisynthetic glycopeptides with enhanced antibacterial activities and improved safety profiles. This Review provides an updated overview of recent advancements made in the development of novel semisynthetic glycopeptides, spanning the period from 2014 to today. A wide range of approaches are covered, encompassing innovative strategies that have delivered semisynthetic glycopeptides with potent activities against Gram-positive bacteria, including drug-resistant strains. We also address recent efforts aimed at developing targeted therapies and advances made in extending the activity of the glycopeptides toward Gram-negative organisms.

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“…Applying this method, selective incorporation of azide moieties on the surface of tumor cells both in vitro and in vivo could be achieved. [35] In the context of our research program on surface engineering with new-to-nature catalyst systems, [36] antibiotics, [37,38] proteins, [39] to biohybrid microswimmers, [40] we became interested in antibody recruiting to cell surfaces.…”

Section: Introductionmentioning

confidence: 99%

Antibody Recognition of Cancer Cells via Glycan Surface Engineering

Szponarski

Gademann

2022

ChemBioChem

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Stimulation of the body's immune system toward tumor cells is now well recognized as a promising strategy in cancer therapy. Just behind cell therapy and monoclonal antibodies, small molecule-based strategies are receiving growing attention as alternatives to direct immune response against tumor cells. However, the development of small-molecule approaches to modulate the balance between stimulatory immune factors and suppressive factors in a targeted way remains a challenge. Here, we report the cell surface functionalization of LS174T cancer cells with an abiotic hapten to recruit antibodies to the cell surface. Metabolic glycoengineering followed by covalent reaction with the hapten results in antibody recognition of the target cells. Microscopy and flow cytometry studies provide compelling evidence that metabolic glycoengineering and small molecule stimulators can be combined to direct antibody recognition.

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Antibiotic Algae by Chemical Surface Engineering

Cited by 19 publications

References 47 publications

Biohybrid Microswimmers Against Bacterial Infections

Biohybrid Microswimmers Against Bacterial Infections

Recent Advances in the Development of Semisynthetic Glycopeptide Antibiotics: 2014–2022

Antibody Recognition of Cancer Cells via Glycan Surface Engineering

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