Engineering of receptor-binding proteins in bacteriophages and phage tail-like bacteriocins

2019 ◽  
Vol 47 (1) ◽  
pp. 449-460 ◽  
Author(s):  
Dorien Dams ◽  
Lone Brøndsted ◽  
Zuzanna Drulis-Kawa ◽  
Yves Briers

AbstractBacteriophages and phage tail-like bacteriocins (PTLBs) rely on receptor-binding proteins (RBPs) located in tail fibers or spikes for an initial and specific interaction with susceptible bacteria. Bacteriophages kill bacteria through a lytic, replicative cycle, whereas PTLBs kill the target through membrane depolarization in a single hit mechanism. Extensive efforts in the engineering of RBPs of both phages and PTLBs have been undertaken to obtain a greater understanding of the structural organization of RBPs. In addition, a major goal of engineering RBPs of phages and PTLBs is the production of antibacterials with a customized spectrum. Swapping of the RBP of phages and PTLBs results in a shift in activity spectrum in accordance with the spectrum of the new RBP. The engineering of strictly virulent phages with new RBPs required significant technical advances in the past decades, whereas the engineering of RBPs of PTLBs relied on the traditional molecular techniques used for the manipulation of bacteria and was thus relatively straightforward. While phages and PTLBs share their potential for specificity tuning, specific features of phages such as their lytic killing mechanism, their self-replicative nature and thus different pharmacokinetics and their potential to co-evolve are clear differentiators compared with PTLBs in terms of their antibacterial use.

Author(s):  
Sascha R. A. Alles ◽  
Anne-Marie Malfait ◽  
Richard J. Miller

Pain is not a simple phenomenon and, beyond its conscious perception, involves circuitry that allows the brain to provide an affective context for nociception, which can influence mood and memory. In the past decade, neurobiological techniques have been developed that allow investigators to elucidate the importance of particular groups of neurons in different aspects of the pain response, something that may have important translational implications for the development of novel therapies. Chemo- and optogenetics represent two of the most important technical advances of recent times for gaining understanding of physiological circuitry underlying complex behaviors. The use of these techniques for teasing out the role of neurons and glia in nociceptive pathways is a rapidly growing area of research. The major findings of studies focused on understanding circuitry involved in different aspects of nociception and pain are highlighted in this article. In addition, attention is drawn to the possibility of modification of chemo- and optogenetic techniques for use as potential therapies for treatment of chronic pain disorders in human patients.


Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 512
Author(s):  
Celine Jacobs ◽  
Lore Lapeire

Soft tissue sarcomas are a group of rare mesenchymal tumors with more than 70 subtypes described. Treatment of these subtypes in an advanced setting is mainly according to a one-size-fits-all strategy indicating a high unmet need of new and more targeted therapeutic options in order to optimize survival. The introduction of advanced molecular techniques in cancer has led to better diagnostics and identification of new therapeutic targets, leading to more personalized treatment and improved prognosis for several cancer types. In sarcoma, a likewise evolution is seen, albeit at a slower pace. This manuscript describes how in the past years advanced molecular profiling in soft tissue sarcomas was able to identify specific and often pathognomonic aberrations, deferring standard sarcoma treatment in favor of more targeted treatment from an oncologist’s point of view.


Aorta ◽  
2021 ◽  
Author(s):  
Igor Vendramin ◽  
Uberto Bortolotti ◽  
Davide Nunzio De Manna ◽  
Andrea Lechiancole ◽  
Sandro Sponga ◽  
...  

AbstractSimultaneous replacement of the ascending aorta and aortic valve has always been a challenging procedure. Introduction of composite conduits, through various ingenious procedures and their modifications, has changed the outlook of patients with aortic valve disease and ascending aorta pathology. In the past 70 years, progress of surgical techniques and prosthetic materials has allowed such patients to undergo radical procedures providing excellent early and long-term results in both young and elderly patients. This article aims to review the most important technical advances in the treatment of aortic valve disease and ascending aorta aneurysms recognizing the important contributions in this field.


2019 ◽  
Vol 5 ◽  
Author(s):  
Oana Teodora Moldovan ◽  
Rannveig Øvrevik Skoglund ◽  
Horia Leonard Banciu ◽  
Alexandra Dinu Cucoș ◽  
Erika Andrea Levei ◽  
...  

In the past 100 years, a decreasing rainfall trend has been recorded on Romanian territory, a trend that continues today. Therefore, realistic estimation of the groundwater resources is crucial, especially for the rural communities lacking the economic power to use alternative sources of drinking water. The groundwater sources used by rural communities in Romania generally originate directly from caves, wells or springs with no proper evaluation of the water quality. Groundwater is exposed to different pollutants, as bats' guano in caves, fertilizers in agricultural areas or livestock (cattle, sheep, goats, etc.) farms on the surface. On the other hand, the water extracted directly from inside the caves is affecting groundwater ecosystems, highly vulnerable to any human impact and neglected by European legislation so far. The project aims to monitor, during two consecutive years, groundwater sources with different degrees of above- and underground pollution, from different regions of Romania. To achieve the goals of the project, a multidisciplinary monitoring strategy that will include measurements of hydrological, physico-chemical and biological (microbiology and aquatic invertebrates’ assessment) parameters alongside the quantification of radon and stable isotopes, rainfall or possible inflows of water. The specific outcomes of this project are: i) to test, develop and validate a new, more rapid and efficient method for monitoring and risk assessment of groundwater sources – and not only – by using molecular techniques, and propose this method to the water agencies in Romania; ii) to propose for Romanian authorities to implement a harmonized coherent methodology to measure radon concentration in water, as a consequence of EURATOM Directive; and iii) to educate local communities that are using groundwater as source for drinking water and raise young people’s awareness on the benefits of ecosystem services provided by the groundwater.


2001 ◽  
Vol 114 (10) ◽  
pp. 1797-1798
Author(s):  
K. Plant

Essential Molecular Biology, Vol. 1, 2nd edn edited by T. A. Brown Oxford University Press (2000) 240 pages. ISBN 0–19-963642-7 pound29.95 I have heard it said (though not to my face) that practical molecular biology is somewhat akin to cookery, and I have to admit (though not to my fellow Molecular Biologists) that there is an element of truth in this. Of course, our ovens are cooler, and our pie dishes smaller, but often it is a case of mixing ingredients in the right proportions and baking at 37 degrees C for an hour. In this book Brown becomes the Delia Smith of molecular biology, starting with how to boil an egg, before proceeding to more complex recipes. It is utterly and unashamedly aimed at the complete novice. As more and more branches of biology use molecular techniques, and as a constant flow of graduates take up the yoke of research, there will always be a demand for this type of manual. Of course, it is possible to find variants of a lot of these methods on the Internet, but, as these often include only the protocol, the complete novice is probably better off with a specifically designed manual. Another option is to go for the kit approach, but, in the same way as opening a tin of beans doesn't make you a chef, I whole heartedly agree with Brown when he says, ‘do not get the idea that using kits is the same as being a molecular biologist.’ In most branches of biology a bit of genuine molecular expertise can only enhance one's future job prospects! One of the things I liked about this book is its no-nonsense style, particularly those chapters written by the Editor. There is plenty of sound advice, not just on the molecular techniques but on how to be a good scientist in general. Although the advice starts with the basics, it isn't patronising to those experienced in other fields. One piece of advice that particularly tickled me was that, if your hand is too unsteady to load a gel, you should give up caffeine; I'm not sure whether the pain would be worth the gain! The first chapter deals with all the basic issues, from planning (not just how to do it, but is it worthy of your time, which is something we should all think about occasionally) to safety (which nasties you'll be using, what precautions to take, with internet sites referenced to fill in the details) and what equipment you'll need to run the experiments. In a nutshell, the rest of the book deals with microbiology for molecular biologists and molecular biology for everyone else. This includes DNA and RNA isolation, electrophoresis and cloning (generating, propagating and identifying recombinant DNA molecules, not the Dolly-the-sheep variety). There is a second volume to the set, which (based on the contents of the first edition) should cover making and screening libraries, the polymerase chain reaction, sequencing and gene expression studies. Bear in mind that to get very far you will need to buy the second volume, which is not yet published. It has been more than a decade since the first edition of this well-known and respected manual was published; so one would think its first update is about due. However, compared with the first edition, most chapters have very few changes. This is probably in the nature of such a basic manual - for example, good microbial practice doesn't change much. Only a couple of chapters have been extensively rewritten; those describing DNA extraction now include more recent resin-based methods. So to the crux of the matter: would I recommend buying it? Well, if you're a complete novice with little backup, I definitely think it is worth investing in a decent manual, and this one does have a nice comfortable feel to it. If you've already got a copy of the previous edition and are wondering whether to upgrade, I would say that the few improvements in these very basic techniques do not really make it worth spending the pound30 that this volume costs. That said, I rather suspect that the second volume, which deals with more complex techniques, will show far more technical advances and should complete your progression from culinary incompetence to cordon bleu.


2019 ◽  
Vol 40 (1) ◽  
pp. 122-130
Author(s):  
Gary G Martin ◽  
Zain Natha ◽  
Nicola Henderson ◽  
Sabi Bang ◽  
Hope Hendry ◽  
...  

Abstract It has become a common expectation for an animal’s guts to be a site for bacterial symbiosis, which may play a role in influencing various aspects of physiology including digestion and immune responses. The presence of a microbiome in the digestive tracts of crustaceans has been demonstrated in the past using molecular techniques and has encouraged manipulations including probiotics to enhance growth rates in cultured species. We suggest, however, that bacteria are restricted to the lumen of the gut and separated from the epithelium by the peritrophic matrix, which prevents their establishment as a permanent component of the gut. The peritrophic matrix, found in most arthropods, is a chitinous sheet containing accessory molecules, and is continuously formed by delamination from the epithelium of the midgut such that the actual surface is constantly being cleaned. The lifted layer then surrounds ingested materials, including microbes, in an impenetrable wrapper compartmentalizing digestive and immune functions. The ectoperitrophic space, lying between the peritrophic matrix and the epithelium, was examined in six species representatives of six groups of crustaceans (Branchiopoda, Amphipoda, Copepoda, and Decapoda) for the presence of microbes using light and transmission electron microscopy as well as fluorescent probes for bacteria. The results suggest that a microbiome is lacking in several common groups of crustaceans.


2017 ◽  
Vol 32 ◽  
pp. 76-84 ◽  
Author(s):  
Zhuoying Liu ◽  
Ting Xiao ◽  
Xiaoyu Peng ◽  
Guangdi Li ◽  
Fang Hu

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