Time-Fractal Modulation—Possible Modulation Effects in Human Therapy

‘Prime-editing’ proposes to replace traditional programmable nucleases (CRISPR-Cas9) using a catalytically impaired Cas9 (dCas9) connected to a engineered reverse transcriptase, and a guide RNA encoding both the target site and the desired change. With just a ‘nick’ on one strand, it is hypothe- sized, the negative, uncontrollable effects arising from double-strand DNA breaks (DSBs) - translocations, complex proteins, integrations and p53 activation - will be eliminated. However, sequencing data pro- vided (Accid:PRJNA565979) reveal plasmid integration, indicating that DSBs occur. Also, looking at only 16 off-targets is inadequate to assert that Prime-editing is more precise. Integration of plasmid occurs in all three versions (PE1/2/3). Interestingly, dCas9 which is known to be toxic in E. coli and yeast, is shown to have residual endonuclease activity. This also affects studies that use dCas9, like base- editors and de/methylations systems. Previous work using hRad51–Cas9 nickases also show significant integration in on-targets, as well as off-target integration [1]. Thus, we show that cellular response to nicking involves DSBs, and subsequent plasmid/Cas9 integration. This is an unacceptable outcome for any in vivo application in human therapy.

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Tackling Pristinamycin IIB Problems: Synthetic Studies toward Some Fluorinated Analogs

Chemistry Proceedings ◽

10.3390/ecsoc-24-08388 ◽

2020 ◽

Vol 3 (1) ◽

pp. 107

Author(s):

Assia Chebieb ◽

Chewki Ziani-Cherif

Keyword(s):

Chemical Structure ◽

Wittig Reaction ◽

Antimicrobial Agents ◽

Synthetic Approach ◽

Solubility In Water ◽

Fluorinated Analogs ◽

Human Therapy ◽

Primary Structures ◽

Synthetic Studies

Streptogramins are potent antibiotics against numerous highly resistant pathogens and therefore are used in last-resort human therapy. These antibiotics are formed of both A- and B-group compounds named pristinamycins that differ in their basic primary structures. Although pristinamycin IIB is among the most interesting antibiotics in this family, it presents numerous problems related to its chemical structure, such as instability at most pH levels, weak solubility in water, and resistance by bacteria. As a response to the need for developing new antimicrobial agents, we have designed a new analog of pristinamycin IIB, based most importantly on the introduction of fluorine atoms. We conjectured indeed that the introduced modifications may solve the above-mentioned problems exhibited by pristinamycin IIB. Our multistep synthetic approach relies on few key reactions, namely a Wittig reaction, a Grubbs reaction, and dihydroxy, -difluoro API (Advanced Pharmaceutical Intermediate) synthesis

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Antibiotic resistance of bacteria isolated from Pagellus erythrinus microplastics and public health

European Journal of Public Health ◽

10.1093/eurpub/ckaa166.253 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

P Laganà ◽

E Fazio ◽

N Spanò ◽

M Bonsignore

Keyword(s):

Antibiotic Resistance ◽

Petri Dish ◽

Anthropogenic Pollution ◽

Normal Structure ◽

Multidrug Resistant ◽

Morphological Properties ◽

Marine Environments ◽

Pagellus Erythrinus ◽

Human Therapy ◽

The Moment

Abstract Microplastics (MPs) are widespread in the aquatic environmental due to anthropogenic pollution and are ingested indifferently by fishes that confuse them with food. In aquatic environment, mechanical stress, UV radiations, chemical and biological actions cause a constant degradation and breakdown of plastic objects into smaller fragments. Mediterranean Sea is characterized by the highest densities of plastics in the world being a closed basin with a complex hydrodynamics. The aim of this work is to evidence the occurrence of microbial adhesions on MPs found in edible Pagellus erythrinus (Linnaeus, 1758) bought in local Sicilian supermarkets and therefore highlight the potential role of microplastics in conveying antibiotic resistance by ingestion of food by humans. The composition and structural-morphological properties of MPs found in the excised gastrointestinal tract (GIT) and gills are identified using different techniques. In particular, microparticles of different nature (plastics, organic components, cellulose-based materials) have been determined following specific Raman signals on a large spectral range (300-3500 cm-1). The Pagellus was dissected, open longitudinally, within a sterile glass Petri dish. The components deemed exogenous to the normal structure of the gills and GIT were collected. Optical microscopy images showed that both the GIT and the gill of Pagellus erythrinus contain MPs of different colors (black, dark blu) and mainly with a fibrous shape. At the moment, microbial assays show the adhesion of Citrobacter and E. coli in some fibers extracted by gills while Vibrio spp was mainly detected in the fibers present in GIT. Bacterial isolates were screened for susceptibility to antibiotics using the Kirby-Bauer test, choosing the molecules most used in human therapy. The results obtained suggest that plastics may contribute to the spread of multiple antibiotic resistance in marine environments underline the relevance of future studies on this topic. Key messages Plastics can serve as vectors for the spread of multiple resistances to antibiotics across marine environments. Further studies on possible vehicles of multidrug-resistant germs carried by food of various kinds are desirable.

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