bims-mricoa 2023-01-22 papers

Issue of 2023–01–22
six papers selected by
Merve Yavuz, Bilkent University

Small. 2023 Jan 20. e2206136

Applications of Bacteria Decorated with Synthetic DNA Constructs.

Pragati K Prasad, Leila Motiei, David Margulies.

The advent of DNA nanotechnology has revolutionized the way DNA has been perceived. Rather than considering it as the genetic material alone, DNA has emerged as a versatile synthetic scaffold that can be used to create a variety of molecular architectures. Modifying such self-assembled structures with bio-molecular recognition elements has further expanded the scope of DNA nanotechnology, opening up avenues for using synthetic DNA assemblies to sense or regulate biological molecules. Recent advancements in this field have lead to the creation of DNA structures that can be used to modify bacterial cell surfaces and endow the bacteria with new properties. This mini-review focuses on the ways by which synthetic modification of bacterial cell surfaces with DNA constructs can expand the natural functions of bacteria, enabling their potential use in various fields such as material engineering, bio-sensing, and therapy. The challenges and prospects for future advancements in this field are also discussed.

Keywords: DNA nanotechnology; cell surface engineering; cell-based theranostics; living materials

DOI: https://doi.org/10.1002/smll.202206136

Cells. 2023 Jan 14. pii: 315. [Epub ahead of print]12(2):

Gradient Magnetic Field Accelerates Division of E. coli Nissle 1917.

Svitlana Gorobets, Oksana Gorobets, Iryna Sharai, Tatyana Polyakova, Vitalii Zablotskii.

Cell-cycle progression is regulated by numerous intricate endogenous mechanisms, among which intracellular forces and protein motors are central players. Although it seems unlikely that it is possible to speed up this molecular machinery by applying tiny external forces to the cell, we show that magnetic forcing of magnetosensitive bacteria reduces the duration of the mitotic phase. In such bacteria, the coupling of the cell cycle to the splitting of chains of biogenic magnetic nanoparticles (BMNs) provides a biological realization of such forcing. Using a static gradient magnetic field of a special spatial configuration, in probiotic bacteria E. coli Nissle 1917, we shortened the duration of the mitotic phase and thereby accelerated cell division. Thus, focused magnetic gradient forces exerted on the BMN chains allowed us to intervene in the processes of division and growth of bacteria. The proposed magnetic-based cell division regulation strategy can improve the efficiency of microbial cell factories and medical applications of magnetosensitive bacteria.

Keywords: bacterial division; biomagnetic effects; intracellular forces; magnetic field; mitosis

DOI: https://doi.org/10.3390/cells12020315

Methods Mol Biol. 2023 ;2617 201-208

Refolding of Proteins Expressed as Inclusion Bodies in E. coli.

Rashmi Sharma, Anupa Anupa, Anurag S Rathore.

Microbial-based biotherapeutics that are produced in Escherichia coli (E. coli) can be generated intracellularly in the form of inclusion bodies (IBs) or in soluble active form in periplasmic space or extracellularly. Overexpression of these biotherapeutics in E. coli leads to formation of insoluble aggregates called inclusion bodies. These IBs contain misfolded and inactive form of proteins which need to be refolded to obtain a functionally active form of proteins. Here, we discuss refolding of E. coli-based recombinant human granulocyte colony-stimulating factor (GCSF), expressed as IBs, and highlight some of the key features associated with the refolding kinetic reaction.

Keywords: Chemical additives; E. coli; GCSF; Inclusion bodies; Protein refolding; Recombinant proteins

DOI: https://doi.org/10.1007/978-1-0716-2930-7_14

Mater Today Bio. 2023 Feb;18 100543

Advances in Escherichia coli Nissle 1917 as a customizable drug delivery system for disease treatment and diagnosis strategies.

Haojie Chen, Pengyu Lei, Hao Ji, Qinsi Yang, Bo Peng, Jiahui Ma, Yimeng Fang, Linkai Qu, Hua Li, Wei Wu, Libo Jin, Da Sun.

With the in-depth and comprehensive study of bacteria and their related ecosystems in the human body, bacterial-based drug delivery system has become an emerging biomimetic platform that can retain the innate biological functions. Benefiting from its good biocompatibility and ideal targeting ability as a biological carrier, Escherichia coli Nissle 1917 (ECN) has been focused on the treatment strategies of inflammatory bowel disease and tumor. The advantage of a bacterial carrier is that it can express exogenous protein while also acting as a natural capsule by releasing drug slowly as a result of its own colonization impact. In order to survive in harsh environments such as the digestive tract and tumor microenvironment, ECN can be modified or genetically engineered to enhance its function and host adaptability. The adoption of ECN carries or expresses drugs which are essential for accurate diagnosis and treatment. This review briefly describes the properties of ECN, the relationship between ECN and inflammation and tumor, and the strategy of using surface modification and genetic engineering to modify ECN as a delivery carrier for disease treatment.

Keywords: Drug delivery system; E. coli Nissle 1917; Genetic engineering; Surface modification

DOI: https://doi.org/10.1016/j.mtbio.2023.100543

Commun Biol. 2023 Jan 17. 6(1): 60

Tumor-specific intracellular delivery: peptide-guided transport of a catalytic toxin.

Curtis A Allred, Claire Gormley, Indu Venugopal, Shunzi Li, Michael J McGuire, Kathlynn C Brown.

There continues to be a need for cancer-specific ligands that can deliver a wide variety of therapeutic cargos. Ligands demonstrating both tumor-specificity and the ability to mediate efficient cellular uptake of a therapeutic are critical to expand targeted therapies. We previously reported the selection of a peptide from a peptide library using a non-small cell lung cancer (NSCLC) cell line as the target. Here we optimize our lead peptide by a series of chemical modifications including truncations, N-terminal capping, and changes in valency. The resultant 10 amino acid peptide has an affinity of <40 nM on four different NSCLC cell lines as a monomer and is stable in human serum for >48 h. The peptide rapidly internalizes upon cell binding and traffics to the lysosome. The peptide homes to a tumor in an animal model and is retained up to 72 h. Importantly, we demonstrate that the peptide can deliver the cytotoxic protein saporin specifically to cancer cells in vitro and in vivo, resulting in an effective anticancer agent.

DOI: https://doi.org/10.1038/s42003-022-04385-7