bims-mricoa 2022-03-06 papers

Issue of 2022‒03‒06
five papers selected by
Merve Yavuz
Bilkent University

Adv Mater. 2022 Mar 03. e2201326

Xinyue Liu, Maria Eugenia Inda, Yong Lai, Timothy K Lu, Xuanhe Zhao.

Living biological systems, ranging from single cells to whole organisms, can sense, process information, and actuate in response to changing environmental conditions. Inspired by living biological systems, engineered living cells and non-living matrices are brought together, which gives rise to the technology of engineered living materials. By designing the functionalities of living cells and the structures of non-living matrices, engineered living materials can be created to detect variability in the surrounding environment and to adjust their functions accordingly, thereby enabling applications in health monitoring, disease treatment, and environmental remediation. Hydrogels, a class of soft, wet, and biocompatible materials, have been widely used as matrices for engineered living cells, leading to the nascent field of engineered living hydrogels. Here, we discuss the interactions between hydrogel matrices and engineered living cells, focusing on how hydrogels influence cell behaviours and how cells affect hydrogel properties. We also discuss the interactions between engineered living hydrogels and their environments, and how these interactions enable versatile applications. Finally, we highlight current challenges facing the field of engineered living hydrogels for their applications in clinical and environmental settings. This article is protected by copyright. All rights reserved.

Keywords: engineered living hydrogels; microbe-material interaction; real-world applications; synthetic biology

DOI: https://doi.org/10.1002/adma.202201326

Genes Dis. 2022 Mar;9(2): 334-346

Ferroptosis: An emerging therapeutic opportunity for cancer.

Liyuan Wang, Xiaoguang Chen, Chunhong Yan.

Ferroptosis, a new form of non-apoptotic, regulated cell death characterized by iron dependency and lipid peroxidation, is involved in many pathological conditions such as neurodegenerative diseases, heart ischemia/reperfusion injury, acute renal failure, and cancer. While metabolic dysfunctions can lead to excessive lipid peroxidation culminating in ferroptotic cell death, glutathione peroxidase 4 (GPX4) resides in the center of a network that functions to prevent lipid hydroperoxides from accumulation, thereby suppressing ferroptosis. Indeed, RSL3 and other small-molecule GPX4 inhibitors can induce ferroptosis in not only cultured cancer cells but also tumor xenografts implanted in mice. Similarly, erastin and other system Xc- inhibitors can deplete intracellular glutathione required for GPX4 function, leading to lipid peroxidation and ferroptosis. As therapy-resistant cancer cells are sensitive to GPX4-targeted therapeutic regimens, the agents capable of inducing ferroptosis hold great promises to improve current cancer therapy. This review will outline the molecular basis of ferroptosis, but focus on the strategies and the agents developed in recent years for therapeutic induction of ferroptosis. The potentials of these ferroptosis-inducing agents, which include system Xc- inhibitors, GPX4 inhibitors, and iron-based nanoparticles, in cancer therapy will be subsequently discussed.

Keywords: Cancer therapy; Erastin; Ferroptosis; GPX4; Lipid peroxidation; Nanomedicine; RSL3; System Xc-

DOI: https://doi.org/10.1016/j.gendis.2020.09.005

Biotechnol Adv. 2022 Feb 27. pii: S0734-9750(22)00028-3. [Epub ahead of print] 107932

Bacterial biofilms as platforms engineered for diverse applications.

Zhong Li, Xinyu Wang, Jie Wang, Xinyi Yuan, Xiaoyu Jiang, Yanyi Wang, Chao Zhong, Dake Xu, Tingyue Gu, Fuhui Wang.

Historically, biofilms have been perceived as problematic or detrimental. However, biofilms possess favorable traits such as self-regeneration, sustainability, scalability, and tunability, which make them candidates for diverse applications. Traditional applications of biofilms, such as environmental remediation, bioleaching, microbial fuel cells, and corrosion protection, are often built on the basis of wild-type or metabolically engineered strains. In this review, we further comment on the design strategies for multiple innovative applications of living functional biofilms. With the integration of signaling pathways, engineering of metabolic pathways and modification of extracellular polymeric substances, living functional biofilms have been constructed by researchers through various strategies. Functional biofilms for diverse applications, including catalysis, electric conduction, bioremediation, and medical therapy have been demonstrated in the literature. The mechanical properties of biofilms can be tuned through genetic editing, metal ion curing and synthetic gene circuits, etc. In addition, the improvement of 3D printing to use bioinks has also achieved significant progresses in fabricating living functional biofilms with specific structures. In the future, the combination of synthetic biology and techniques from other disciplines will lead to practical large-scale applications of biofilms.

Keywords: 3D printing; Biofilms; Living functional biofilms; Mechanical property; Synthetic biology

DOI: https://doi.org/10.1016/j.biotechadv.2022.107932

Trends Pharmacol Sci. 2022 Feb 26. pii: S0165-6147(22)00026-8. [Epub ahead of print]

Emerging strategies for engineering Escherichia coli Nissle 1917-based therapeutics.

Jason P Lynch, Lisa Goers, Cammie F Lesser.

Engineered microbes are rapidly being developed for the delivery of therapeutic modalities to sites of disease. Escherichia coli Nissle 1917 (EcN), a genetically tractable probiotic with a well-established human safety record, is emerging as a favored chassis. Here, we summarize the latest progress in rationally engineered variants of EcN for the treatment of infectious diseases, metabolic disorders, and inflammatory bowel diseases (IBDs) when administered orally, as well as cancers when injected directly into tumors or the systemic circulation. We also discuss emerging studies that raise potential safety concerns regarding these EcN-based strains as therapeutics due to their secretion of a genotoxic colibactin that can promote the formation of DNA double-stranded breaks in mammalian DNA.

Keywords: Escherichia coli Nissle 1917; bioengineering; colibactin; microbial therapeutics; synthetic biology

DOI: https://doi.org/10.1016/j.tips.2022.02.002

Front Cell Infect Microbiol. 2022 ;12 825856

Therapeutic Antibodies Against Shiga Toxins: Trends and Perspectives.

Izabella de Macedo Henrique, Flavia Sacerdoti, Raissa Lozzardo Ferreira, Camila Henrique, Maria Marta Amaral, Roxane Maria Fontes Piazza, Daniela Luz.

Shiga toxins (Stx) are AB5-type toxins, composed of five B subunits which bind to Gb3 host cell receptors and an active A subunit, whose action on the ribosome leads to protein synthesis suppression. The two Stx types (Stx1 and Stx2) and their subtypes can be produced by Shiga toxin-producing Escherichia coli strains and some Shigella spp. These bacteria colonize the colon and induce diarrhea that may progress to hemorrhagic colitis and in the most severe cases, to hemolytic uremic syndrome, which could lead to death. Since the use of antibiotics in these infections is a topic of great controversy, the treatment remains supportive and there are no specific therapies to ameliorate the course. Therefore, there is an open window for Stx neutralization employing antibodies, which are versatile molecules. Indeed, polyclonal, monoclonal, and recombinant antibodies have been raised and tested in vitro and in vivo assays, showing differences in their neutralizing ability against deleterious effects of Stx. These molecules are in different phases of development for which we decide to present herein an updated report of these antibody molecules, their source, advantages, and disadvantages of the promising ones, as well as the challenges faced until reaching their applicability.

Keywords: Shiga toxin-producing E. coli; Stx toxins; antibodies; therapy; trends

DOI: https://doi.org/10.3389/fcimb.2022.825856