scholarly journals Synthetic Biology – Friend or Foe? What Kind of Threats Should We Expect?

2021 ◽  
Vol 5 (2) ◽  
pp. 103-122
Keyword(s):  
Synthetic Biology ◽  
Science Fiction ◽  
Pathogenic Bacteria ◽  
Human Microbiome ◽  
Toxic Chemicals ◽  
Pathway Engineering ◽  
Zinc Finger Nucleases ◽  
Biological Warfare ◽  
Dual Use ◽  
Human Immune System

Synthetic biology is a newly emerging branch of dual-use technology. It is a combination of biology and different branches of engineering. The aim of this article is to show the main technological methods of synthetic biology and to give specific examples of its use to create new types of biological agents and methods of biological warfare, previously unthinkable and presented only in science fiction. Basic tools and techniques of synthetic biology are: DNA synthesis and DNA sequencing; «chassis», i.e. host system harboring the genetic toolbox for expression of the desired genes, delivered by suitable vectors, of the engineered biological pathway; engineering of transcription systems that do not deplete the resources of the cell (synthetic promotors and transcription factors); genome modification tools (CRISPR/Cas9 nuclease, zinc finger nucleases, TALE nucleases, meganucleases); computer-aided tools (involved in basic structural design and synthesis; in network design; in prediction of behavior/function/response). Synthetic biology has already demonstrared its capabilities in re-creating known pathogenic viruses and pathogenic bacteria; in making existing pathogenic bacteria and viruses more dangerous for humans; in creating new pathogens; in manufacturing toxic chemicals or biochemicals by exploiting natural and artificial metabolic pathways; in making toxic chemicals and biochemicals via in situ synthesis; in modifying the human microbiome; in modifying the human immune system; in modifying the human genome (through addition, deletion, or modification of genes or through epigenetic changes that modify gene expression and can pass from parent to child during reproduction and thus spread a genetic change through the population over time). The article discusses in detail the possibilities of synthetic biology for the development of new means of biological warfare. The author believes that it is necessary not only to constantly monitor these new dual-use biotechnologies, but also to improve traditional and scientific methods of their monitoring.

scholarly journals Identification of an N-acetylneuraminic acid-presenting bacteria isolated from a human microbiome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhen Han ◽  
Peter S. Thuy-Boun ◽  
Wayne Pfeiffer ◽  
Vincent F. Vartabedian ◽  
Ali Torkamani ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Human Microbiome ◽  
Host Immunity ◽  
Rrna Gene ◽  
Metabolic Labeling ◽  
Selective Labeling ◽  
Fecal Microbiome ◽  
Acetylneuraminic Acid ◽  
Intestinal Mucus ◽  
Microbial Systems

AbstractN-Acetylneuraminic acid is the most abundant sialic acid (SA) in humans and is expressed as the terminal sugar on intestinal mucus glycans. Several pathogenic bacteria harvest and display host SA on their own surfaces to evade Siglec-mediated host immunity. While previous studies have identified bacterial enzymes associated with SA catabolism, no reported methods permit the selective labeling, tracking, and quantitation of SA-presenting microbes within complex multi-microbial systems. We combined metabolic labeling, click chemistry, 16S rRNA gene, and whole-genome sequencing to track and identify SA-presenting microbes from a cultured human fecal microbiome. We isolated a new strain of Escherichia coli that incorporates SA onto its own surface and encodes for the nanT, neuA, and neuS genes necessary for harvesting and presenting SA. Our method is applicable to the identification of SA-presenting bacteria from human, animal, and environmental microbiomes, as well as providing an entry point for the investigation of surface-expressed SA-associated structures.

scholarly journals Cross-kingdom inhibition of bacterial virulence and communication by probiotic yeast metabolites

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Orit Malka ◽  
Dorin Kalson ◽  
Karin Yaniv ◽  
Reut Shafir ◽  
Manikandan Rajendran ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Gut Microbiome ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Molecular Mechanisms ◽  
Human Microbiome ◽  
Cell Communication ◽  
Probiotic Yeast ◽  
Gut Pathogen ◽  
Cell Cell

Abstract Background Probiotic milk-fermented microorganism mixtures (e.g., yogurt, kefir) are perceived as contributing to human health, and possibly capable of protecting against bacterial infections. Co-existence of probiotic microorganisms are likely maintained via complex biomolecular mechanisms, secreted metabolites mediating cell-cell communication, and other yet-unknown biochemical pathways. In particular, deciphering molecular mechanisms by which probiotic microorganisms inhibit proliferation of pathogenic bacteria would be highly important for understanding both the potential benefits of probiotic foods as well as maintenance of healthy gut microbiome. Results The microbiome of a unique milk-fermented microorganism mixture was determined, revealing a predominance of the fungus Kluyveromyces marxianus. We further identified a new fungus-secreted metabolite—tryptophol acetate—which inhibits bacterial communication and virulence. We discovered that tryptophol acetate blocks quorum sensing (QS) of several Gram-negative bacteria, particularly Vibrio cholerae, a prominent gut pathogen. Notably, this is the first report of tryptophol acetate production by a yeast and role of the molecule as a signaling agent. Furthermore, mechanisms underscoring the anti-QS and anti-virulence activities of tryptophol acetate were elucidated, specifically down- or upregulation of distinct genes associated with V. cholerae QS and virulence pathways. Conclusions This study illuminates a yet-unrecognized mechanism for cross-kingdom inhibition of pathogenic bacteria cell-cell communication in a probiotic microorganism mixture. A newly identified fungus-secreted molecule—tryptophol acetate—was shown to disrupt quorum sensing pathways of the human gut pathogen V. cholerae. Cross-kingdom interference in quorum sensing may play important roles in enabling microorganism co-existence in multi-population environments, such as probiotic foods and the gut microbiome. This discovery may account for anti-virulence properties of the human microbiome and could aid elucidating health benefits of probiotic products against bacterially associated diseases.

scholarly journals COVID-19 Lockdowns May Reduce Resistance Genes Diversity in the Human Microbiome and the Need for Antibiotics

2021 ◽  
Vol 22 (13) ◽  
pp. 6891
Author(s):  
João S. Rebelo ◽  
Célia P. F. Domingues ◽  
Francisco Dionisio ◽  
Manuel C. Gomes ◽  
Ana Botelho ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Human Microbiome ◽  
Antibiotic Resistance Genes ◽  
Public Health Problem ◽  
Small World ◽  
Physical Contact ◽  
Hygiene Measures

Recently, much attention has been paid to the COVID-19 pandemic. Yet bacterial resistance to antibiotics remains a serious and unresolved public health problem that kills hundreds of thousands of people annually, being an insidious and silent pandemic. To contain the spreading of the SARS-CoV-2 virus, populations confined and tightened hygiene measures. We performed this study with computer simulations and by using mobility data of mobile phones from Google in the region of Lisbon, Portugal, comprising 3.7 million people during two different lockdown periods, scenarios of 40 and 60% mobility reduction. In the simulations, we assumed that the network of physical contact between people is that of a small world and computed the antibiotic resistance in human microbiomes after 180 days in the simulation. Our simulations show that reducing human contacts drives a reduction in the diversity of antibiotic resistance genes in human microbiomes. Kruskal–Wallis and Dunn’s pairwise tests show very strong evidence (p < 0.000, adjusted using the Bonferroni correction) of a difference between the four confinement regimes. The proportion of variability in the ranked dependent variable accounted for by the confinement variable was η2 = 0.148, indicating a large effect of confinement on the diversity of antibiotic resistance. We have shown that confinement and hygienic measures, in addition to reducing the spread of pathogenic bacteria in a human network, also reduce resistance and the need to use antibiotics.

scholarly journals Walls talk: Microbial biogeography of homes spanning urbanization

2016 ◽  
Vol 2 (2) ◽  
pp. e1501061 ◽  
Author(s):  
Jean F. Ruiz-Calderon ◽  
Humberto Cavallin ◽  
Se Jin Song ◽  
Atila Novoselac ◽  
Luis R. Pericchi ◽  
...  
Keyword(s):  
Architectural Design ◽  
Human Microbiome ◽  
Outdoor Environment ◽  
Human Immune System ◽  
Developmental Exposure ◽  
Immune Development ◽  
Indoor Space ◽  
Microbial Biogeography ◽  
Microbiome Diversity ◽  
Outdoor Environments

Westernization has propelled changes in urbanization and architecture, altering our exposure to the outdoor environment from that experienced during most of human evolution. These changes might affect the developmental exposure of infants to bacteria, immune development, and human microbiome diversity. Contemporary urban humans spend most of their time indoors, and little is known about the microbes associated with different designs of the built environment and their interaction with the human immune system. This study addresses the associations between architectural design and the microbial biogeography of households across a gradient of urbanization in South America. Urbanization was associated with households’ increased isolation from outdoor environments, with additional indoor space isolation by walls. Microbes from house walls and floors segregate by location, and urban indoor walls contain human bacterial markers of space use. Urbanized spaces uniquely increase the content of human-associated microbes—which could increase transmission of potential pathogens—and decrease exposure to the environmental microbes with which humans have coevolved.

scholarly journals Endotoxin, Capsule, and Bacterial Attachment Contribute to Neisseria meningitidis Resistance to the Human Antimicrobial Peptide LL-37

2009 ◽  
Vol 191 (12) ◽  
pp. 3861-3868 ◽  
Author(s):  
Allison Jones ◽  
Miriam Geörg ◽  
Lisa Maudsdotter ◽  
Ann-Beth Jonsson
Keyword(s):  
Antimicrobial Peptide ◽  
Neisseria Meningitidis ◽  
Pathogenic Bacteria ◽  
Wild Type Strain ◽  
Bacterial Attachment ◽  
Bacterial Membrane ◽  
Wild Type ◽  
Human Immune System ◽  
Sublethal Doses ◽  
Human Immune

ABSTRACT Pathogenic bacteria have evolved numerous mechanisms to evade the human immune system and have developed widespread resistance to traditional antibiotics. We studied the human pathogen Neisseria meningitidis and present evidence of novel mechanisms of resistance to the human antimicrobial peptide LL-37. We found that bacteria attached to host epithelial cells are resistant to 10 μM LL-37 whereas bacteria in solution or attached to plastic are killed, indicating that the cell microenvironment protects bacteria. The bacterial endotoxin lipooligosaccharide and the polysaccharide capsule contribute to LL-37 resistance, probably by preventing LL-37 from reaching the bacterial membrane, as more LL-37 reaches the bacterial membrane on both lipooligosaccharide-deficient and capsule-deficient mutants whereas both mutants are also more susceptible to LL-37 killing than the wild-type strain. N. meningitidis bacteria respond to sublethal doses of LL-37 and upregulate two of their capsule genes, siaC and siaD, which further results in upregulation of capsule biosynthesis.

scholarly journals Enhanced guide-RNA Design and Targeting Analysis for Precise CRISPR Genome Editing of Single and Consortia of Industrially Relevant and Non-Model Organisms

2017 ◽  
Author(s):  
Brian J. Mendoza ◽  
Cong T. Trinh
Keyword(s):  
Metabolic Engineering ◽  
Synthetic Biology ◽  
Genome Editing ◽  
Population Analysis ◽  
Strain Engineering ◽  
Pathway Engineering ◽  
Model Organisms ◽  
Guide Rna ◽  
Novel Applications ◽  
Rna Design

AbstractMotivationGenetic diversity of non-model organisms offers a repertoire of unique phenotypic features for exploration and cultivation for synthetic biology and metabolic engineering applications. To realize this enormous potential, it is critical to have an efficient genome editing tool for rapid strain engineering of these organisms to perform novel programmed functions.ResultsTo accommodate the use of CRISPR/Cas systems for genome editing across organisms, we have developed a novel method, named CASPER (CRISPR Associated Software for Pathway Engineering and Research), for identifying on- and off-targets with enhanced predictability coupled with an analysis of non-unique (repeated) targets to assist in editing any organism with various endonucleases. Utilizing CASPER, we demonstrated a modest 2.4% and significant 30.2% improvement (F-test, p<0.05) over the conventional methods for predicting on- and off-target activities, respectively. Further we used CASPER to develop novel applications in genome editing: multitargeting analysis (i.e. simultaneous multiple-site modification on a target genome with a sole guide-RNA (gRNA) requirement) and multispecies population analysis (i.e. gRNA design for genome editing across a consortium of organisms). Our analysis on a selection of industrially relevant organisms revealed a number of non-unique target sites associated with genes and transposable elements that can be used as potential sites for multitargeting. The analysis also identified shared and unshared targets that enable genome editing of single or multiple genomes in a consortium of interest. We envision CASPER as a useful platform to enhance the precise CRISPR genome editing for metabolic engineering and synthetic biology applications.

scholarly journals Opportunities, Challenges, and Future Considerations for Top-Down Governance for Biosecurity and Synthetic Biology

2021 ◽  
pp. 37-58
Author(s):  
R. Alexander Hamilton ◽  
Ruth Mampuys ◽  
S. E. Galaitsi ◽  
Aengus Collins ◽  
Ivan Istomin ◽  
...  
Keyword(s):  
Synthetic Biology ◽  
Genetic Engineering ◽  
Dna Sequencing ◽  
Environmental Sustainability ◽  
Gene Editing ◽  
Dual Use ◽  
Top Down ◽  
Modern Biology ◽  
The Creation

AbstractSynthetic biology promises to make biology easier to engineer (Endy 2005), enabling more people in less formal research settings to participate in modern biology. Leveraging advances in DNA sequencing and synthesis technologies, genetic assembly methods based on standard biological parts (e.g. BioBricks), and increasingly precise gene-editing tools (e.g. CRISPR), synthetic biology is helping increase the reliability of and accessibility to genetic engineering. Although potentially enabling tremendous opportunities for the advancement of the global bioeconomy, opening new avenues for the creation of health, wealth and environmental sustainability, the possibility of a more ‘democratic’ (widely accessible) bioengineering capability could equally yield new opportunities for accidental, unintended or deliberate misuse. Consequently, synthetic biology represents a quintessential ‘dual-use’ biotechnology – a technology with the capacity to enable significant benefits and risks (NRC 2004).

scholarly journals Anabiosis and the Liminal Geographies of De/extinction

2020 ◽  
Vol 12 (1) ◽  
pp. 321-345
Author(s):  
Adam Searle
Keyword(s):  
Synthetic Biology ◽  
Science Fiction ◽  
Genetic Material ◽  
Turn Of The Millennium ◽  
Suspended Animation ◽  
Work In Progress ◽  
Iberian Ibex ◽  
Dead State ◽  
Recent Developments ◽  
Woolly Mammoth

Abstract The spectacle of de-extinction is often forward facing at the interface of science fiction and speculative fact, haunted by extinction’s pasts. Missing from this discourse, however, is a robust theorization of de-extinction in the present. This article presents recent developments in the emergent fields of resurrection biology and liminality to conceptualize the anabiotic (not living nor dead) state of de/extinction. Through two stories, this article explores the epistemological perturbation caused by the suspended animation of genetic material. Contrasting the genomic stories of the bucardo, a now extinct subspecies of Iberian ibex whose genome was preserved before the turn of the millennium, and the woolly mammoth, whose genome is still a work in progress, the author poses questions concerning the existential authenticity of this genomic anabiosis. They serve as archetypal illustrations of salvaged and synthesized anabiotic creatures. De/extinction is presented as a liminal state of being, both living and dead, both fact and fiction, a realm that we have growing access to through the proliferation of synthetic biology and cryopreservation. The article concludes through a presentation of anabiotic geographies, postulating on the changing biocultural significances we attach to organisms both extinct and extant, and considering their implications for the contemporary extinction crisis.

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