Articles of the Month 2020
Archive of previous entries
Human breastmilk contains complex sugars known as human milk oligosaccharides (HMOs) that do not provide energy but instead improve the health of breastfed infants by preventing infections, promoting the growth of healthy gut bacteria, and supporting normal development. HMOs are not present in typical formula products so bottle-fed infants miss out on these benefits. In October's paper of the month, Parschat et al. describe a new way to produce 2'-fucosyllactose (the most abundant HMO) by bacterial fermentation, starting from sucrose. Although this HMO has been produced by fermentation before, the process required lactose, which is more expensive to source. The new method involves the introduction of a metabolic pathway for 2'-fucosyllactose and can easily be adapted to produce other HMOs. In the future, this could allow the development of formula products that provide a balanced selection of HMOs.
Article details: Parschat K et al. (2020) High-titer de novo biosynthesis of the predominant human milk oligosaccharide 2'-fucosyllactose from sucrose in Escherichia coli. ACS Synth Biol 9 (10) 2784–2796.
Image shows the main HMOs in human breastmilk (mothers with the more common secretor phenotype) with the size of the circles representing proportional content (2'-FL = 2'-fucosyllactose). Left column = neutral, right column = charged. Top row = fucosylated, bottom row = non-fucosylated. Major components are named and empty circles represent minor unnamed components.
Image credit: TRM Ltd.
Limestone and marble structures are highly vulnerable to weathering, which is caused by a combination of acid rain and pollution, the latter resulting in the formation of unsightly black crust. One promising rejuvenation strategy is the use of microbes that precipitate calcium carbonate, replacing the material lost by corrosion. In September’s article of the month, Andreolli et al. show that bacteria isolated from the black crusts on stone monuments can be enriched by cultivation in medium containing polycyclic aromatic hydrocarbons and used for the consolidation of damaged stone by applying them in a gel layer, which encourages the formation of a natural biofilm. Calcified bacterial cells were shown to fill the pores in the stone and increase the calcium carbonate content by more than 100%. This could facilitate the restoration of damaged stone buildings and monuments without resorting to modern construction materials.
Article details: Andreolli M et al. (2020) Bacteria from black crusts on stone monuments can precipitate CaCO3 allowing the development of a new bio-consolidation protocol for ornamental stone. Intl Biodet Biodeg 153, 105031.
Image is a stone gargoyle on the Neues Rathaus (Marienplatz, Munich, Germany) showing acid rain damage and black crust formation.
COVID-19 has placed extreme pressure on healthcare systems around the world, leading to shortages of ventilators, personal protective equipment and intensive care beds. One of the issues facing governments trying to deal with the pandemic is that a permanent state of preparedness would be wasteful, with equipment, personnel and facilities standing idle most of the time. This would be especially challenging for reagents with a limited shelf life, such as testing kits. August's article of the month is a correspondence article in Nature Biotechnology, coauthored by Steven Webb (Global Institute for Food Security), Richard Twyman (TRM Ltd) and Maurice Moloney (AgritecKnowledge LLC). The authors argue that the pandemic response can be addressed by using agricultural technology as an emergency resource. The technology routinely used for crop breeding, seed testing and disease monitoring in agriculture is very similar to that used for medical diagnostics and tracing. With appropriate training, agtech laboratories already accustomed to handling hundreds of samples per day could switch to medical tests in a future pandemic scenario.
Article details: Webb SR, Twyman RM & Moloney M (2020) Agtech infrastructure for pandemic preparedness. Nature Biotechnol 38, 1025–1027.
Image shows a nasopharyngeal swab test.
Image credit: Nature Biotechnology
Checkpoint inhibitor therapy is a type of cancer treatment that blocks the ability of tumors to suppress the immune system. If successful, checkpoint inhibitors allow the immune system to produce active T cells that attack and destroy the tumor. However, this approach only works if the tumor expresses checkpoint regulators such as CTLA4, PD-1 or PD-L1. In July's article of the month, Wang & Steinmetz show that the injection of Cowpea mosaic virus into tumors increases the expression of checkpoint regulators and therefore makes checkpoint inhibitor therapy more successful. They prolonged the survival of three mouse cancer models, as well as protecting them against subsequent tumors. In the future, plant viruses could be tested for their ability to stimulate the tumor environment and thus enhance checkpoint inhibitor therapy in humans.
Article details: Wang C & Steinmetz NF (2020) A combination of Cowpea mosaic virus and immune checkpoint therapy synergistically improves therapeutic efficacy in three tumor models. Adv Funct Mater 30 (27) 2002299.
Image shows a cancer drug target trapped in an inactive state by a small-molecule inhibitor
Image credit: NCI/Sriram Subramaniam.
Parasitoid wasps lay their eggs in or on other insects, providing a source of food for the developing larvae. Some allow the host insect to continue developing, but others, known as idiobionts, arrest the development of the host and sabotage its immune system. It is not clear how this is achieved. In June's article of the month, Özbek et al. show that the parasitoid wasp Pimpla turionellae takes control of host gene expression, switching off genes related to two important developmental hormones as well as those involved in host immunity and defense responses. The reprogramming of host gene expression is controlled epigenetically, by disrupting normal DNA methylation, histone acetylation and miRNA expression. Parasitoid wasps therefore appear to promote the survival of their offspring by hijacking the key mechanisms of gene regulation in the host to interfere with immunity and development.
Article details: Özbek R et al. (2020) Reprograming of epigenetic mechanisms controlling host insect immunity and development in response to egg-laying by a parasitoid wasp. Proc Biol Sci 287 (1928) 20200704.
Image shows an adult parasitoid wasp of the species Pimpla turionellae.
Image credit: Gail Hampshire (CC BY-SA 2.0).
Plant viruses can be developed as vaccines by engineering them to display proteins or peptides from other viruses responsible for diseases in humans. This is advantageous for several reasons: plant viruses are safe because they do not replicate in humans, they are effective because they induce a strong immune response, and they are easy to produce in large quantities using plants. But plant viruses can also be engineered to carry human peptides that induce immunotolerance, and the resulting therapeutic vaccines can be used to treat autoimmune disorders. In May's article of the month, Zampieri et al. show how plant viruses carrying major autoantigens associated with type 1 diabetes and rheumatoid arthritis can induce immunotolerance in mice. Vaccination completely prevented the onset of diabetes and reduced the severity of arthritis symptoms. The peptides were carried by different plant viruses that triggered different but overlapping immunotolerance mechanisms. These results could lead to clinical tests in humans and ultimately to new treatments for autoimmune disorders.
Article details: Zampieri R et al. (2020) Prevention and treatment of autoimmune diseases with plant virus nanoparticles. Sci Adv 6 (19) eaaz0295.
Image shows computer models of Cowpea mosaic virus, one of the two viruses used in this study to carry human autoantigens.
Image credit: Thomas Splettstoesser (CC BY-SA 3.0)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for the current COVID-19 pandemic. There is a massive international effort underway to develop diagnostic reagents, vaccines and antiviral drugs in a bid to slow down the spread of the disease and save lives. One part of that international effort involves the plant science research community, uniting researchers and commercial enterprises from around the world to achieve the rapid supply of protein antigens and antibodies for diagnostic kits, and scalable production systems for the emergency manufacturing of vaccines and antiviral drugs. In April's article of the month, Capell et al. discuss some of the ways in which plants are being used in the fight against COVID-19 and how they might be used in the future against this and other pandemics.
Article details: Capell T et al. (2020) Potential applications of plant biotechnology against SARS-CoV-2. Trends Plant Sci 25 (7) 635–643.
Image shows the structure of SARS-CoV-2.
Image credit: CDC/Alissa Eckert/Dan Higgins.
Insects have conquered many environments and are particularly adept at overcoming microbial pathogens, making them useful resources for the discovery of new antibiotics. The comparative analysis of diverse insect taxa has shown that different groups have favored the expansion and contraction of different gene families encoding antimicrobial peptides, reflecting the unique challenges in their environment. In our article of the month for March, Shelomi et al. investigate the profile of antimicrobial peptides produced by stick insects by comprehensive RNA sequencing in specimens of Peruphasma schultei injected with microbial cocktails to induce a strong immune response. This revealed the induction of many different types of antimicrobial peptide, including multiple cysteine-rich peptides expressed at very high levels and a uniquely high number of lipopolysaccharide-binding protein sequences. The analysis of diverse insects representing a variety of habitats will help to increase the number of candidate antibiotics for further analysis.
Article details: Shelomi M et al. (2020) The unique antimicrobial peptide repertoire of stick insects. Dev Comp Immunol 103, 103471.
The primary component of most fungal cell walls is chitin, a natural polymer also found in the shells of crustaceans and insects. The human immune system recognizes chitin and can therefore repel most fungal pathogens. Some fungi produce enzymes known as chitin deacetylases that convert their cell wall chitin into a modified form known as chitosan, but incomplete conversion leads to the production of chitosan structures with multiple acetyl groups that still alert the immune system. In February's article of the month, Hembach et al. show how the aggressive fungal pathogen Cryptococcus neoformans has solved this problem by producing a deacetylase known as Cda4 that prefers chitosan as a substrate, thereby removing even more of the acetyl groups and forming a version of chitosan that is no longer perceived as a danger signal. The identification of this key enzyme provides a target for the development of new drugs to prevent cryptococcosis.
Article details: Hembach L et al. (2020) Unique subsite specificity and potential natural function of a chitosan deacetylase from the human pathogen Cryptococcus neoformans. Proc Natl Acad Sci USA 117 (7) 3551–3559.
Image shows encapsulated cells of the yeast Cryptococcus neoformans.
Image credit: CDC/Dr Leanor Haley.
Natural enzymes are usually optimized for industrial applications by introducing mutations that improve properties such as stability, substrate selection or catalytic turnover. Enzyme libraries can be combined with activity assays to screen large numbers of variants, and this is sufficient to screen all possible individual mutations at all sites. However, combinations of two or more mutations increase the number of potential variants far beyond current screening capabilities, and some kind of rational selection must be implemented to identify promising candidates. In January's article of the month, Ostafe et al. use machine learning to find the optimal combination of five independent mutations in the enzyme glucose oxidase, leading to an enzyme variant that remains active across a broad pH range and shows greater specificity for two different mediators. Machine learning can therefore be used to predict structure–activity relationships and streamline the optimization of enzymes by directed evolution.
Article details: Ostafe R et al. (2020) One‐shot optimization of multiple enzyme parameters: Tailoring glucose oxidase for pH and electron mediators. Biotechnol Bioeng 117 (1) 17–29.