Month: May 2020

The draft genome of Staphylococcus warneri TRPF4, a bacteriocin producer with potent activity against the causative agent of Legionnaires’ Disease

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In this work, we present the draft genome sequence of Staphylococcus warneri strain TRPF4 consisting of 2,634,550 bp with a G + C content of 32.4%. The genome sequence includes 2466 protein-coding genes, 11 rRNAs and 62 tRNAs, in 33 contigs. Applying the Rapid Annotation using Subsystem Technology (RAST) a total of 1322 protein-coding genes were assigned to 393 subsystems.

Also, a set of 1286 protein-coding genes with designated functions were assigned to 21 categories in the Cluster of Orthologous Groups (COG) database.

Further analysis of BAGEL3 software demonstrated that the TRPF4 genome contains two gene clusters responsible for the synthesis of three bacteriocins, one warnericin RK and two delta-lysins. Besides, a novel delta-lysin of 3.48 kDa was identified for the first time.

The three predicted bacteriocins were chemically synthesized and screened for the antimicrobial activity against a range of pathogens, exhibiting a potent and specific antimicrobial activity counter to L. pneumophila, with minimum inhibitory concentrations (MIC) ranging from 1.9 to 7.8 µg mL-1.

The draft genome of Staphylococcus warneri TRPF4, a bacteriocin producer with potent activity against the causative agent of Legionnaires' Disease
The draft genome of Staphylococcus warneri TRPF4, a bacteriocin producer with potent activity against the causative agent of Legionnaires’ Disease

These results indicate that the strain TRPF4 can produce bacteriocins with anti-Legionella activity. This was verified by the extracting the bacteriocins from the fermentation broth and testing against L. pneumophila. Additionally, the strain TRPF4 exhibited no cytotoxicity in mammalian cell lines.

In summary, the genomic sequences and in vitro assays demonstrated the potential application of bacteriocins from S. warneri TRPF4 as a scaffold for further development of drugs against L. pneumophila, the causative agent of Legionnaires’ Disease.

by- later florida

Copy number alterations (CNAs) play an important role in molding the genomes of breast cancers and have been shown to be clinically useful for prognostic and therapeutic purposes. However, our knowledge of intra-tumoral genetic heterogeneity of this important class of somatic alterations is limited.

Here, using single-cell sequencing, we comprehensively map out the facets of copy number alteration heterogeneity in a cohort of breast cancer tumors. Ou/var/www/html/elife/12-05-2020/backup/r analyses reveal: genetic heterogeneity of non-tumor cells (i.e. stroma) within the tumor mass; the extent to which copy number heterogeneity impacts breast cancer genomes and the importance of both the genomic location and dosage of sub-clonal events;

the pervasive nature of genetic heterogeneity of chromosomal amplifications; and the association of copy number heterogeneity with clinical and biological parameters such as polyploidy and estrogen receptor negative status.

Our data highlight the power of single-cell genomics in dissecting, in its many forms, intra-tumoral genetic heterogeneity of CNAs, the magnitude with which CNA heterogeneity affects the genomes of breast cancers, and the potential importance of CNA heterogeneity in phenomena such as therapeutic resistance and disease relapse.

Gene Silencing in the Liver Fluke Fasciola hepatica: RNA Interference

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The chronic infection with the liver fluke of the genus Fasciola spp. is the most prevalent foodborne trematodiasis, affecting at least one-fourth of the world livestock grazing in areas where the parasite is present. Moreover, fascioliasis is considered a major zoonosis mainly in rural areas of central South America, Northern Africa, and Central Asia.

Increasing evidences of resistance against triclabendazole may compromise its use as drug of choice; thus, novel control strategies are desperately needed.

Functional genomic approaches play a key role in the validation and characterization of new targets for drug and vaccine development. So far, RNA interference has been the only gene silencing approach successfully employed in liver flukes of the genus Fasciola spp. Herein, we describe a detailed step-by-step protocol to perform gene silencing mediated by RNAi in Fasciola hepatica.

Gene Silencing in the Liver Fluke Fasciola hepatica: RNA Interference
Gene Silencing in the Liver Fluke Fasciola hepatica: RNA Interference

Introduction Although bibliometric analyses have been performed in the past on cancer and genomics, little is known about the most frequently cited articles specifically related to cancer epigenetics.

Therefore, the purpose of this study is to use citation count to identify those papers in the scientific literature that have made key contributions in the field of cancer epigenetics and identify key driving forces behind future investigations. Materials and methods The Thomas Reuters Web of Science services was queried for the years 1980-2018 without language restrictions.

Articles were sorted in descending order of the number of times they were cited in the Web of Science database by other studies, and all titles and abstracts were screened to identify the research areas of the top 100 articles. The number of citations per year was calculated.

Results We identified the 100 most-cited articles on cancer epigenetics, which collectively had been cited 147,083 times at the time of this writing. The top-cited article was cited 7,124 times, with an average of 375 citations per year since publication.

In the period 1980-2018, the most prolific years were the years 2006 and 2010, producing nine articles, respectively. Twenty-eight unique journals contributed to the 100 articles, with the Nature journal contributing most of the articles (n=22).

The most common country of article origin was the United States of America (n=78), followed by Germany (n=4), Switzerland (n=4), Japan (n=3), Spain (n=2), and United Kingdom (n=2). Conclusions In this study, the 100 most-cited articles in cancer epigenetics were examined, and the contributions from various authors, specialties, and countries were identified.

Cancer epigenetics is a rapidly growing scientific field impacting translational research in cancer screening, diagnosis, classification, prognosis, and targeted treatments. Recognition of important historical contributions to this field may guide future investigations.

Salmon immunological defense and interplay with the modulatory capabilities of its ectoparasite Lepeophtheirus salmonis.

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The salmon louse Lepeophtheirus salmonis (Lsal) is an ectoparasitic copepod that exerts immunomodulatory and physiological effects on its host Atlantic salmon.

Over 30 years of research on louse biology, control, host responses and the host-parasite relationship has provided a plethora of information on the intricacies of host resistance and parasite adaptation.

Salmon immunological defense and interplay with the modulatory capabilities of its ectoparasite Lepeophtheirus salmonis.
Salmon immunological defense and interplay with the modulatory capabilities of its ectoparasite Lepeophtheirus salmonis.

Atlantic salmon exhibit temporal and spatial impairment of the immune system and wound healing ability during infection. This immunosuppression may render Atlantic salmon less tolerant to stress and other confounders associated with current management strategies. Contrasting susceptibility of salmonid hosts exists and early pro-inflammatory Th1 type responses are associated with resistance.

Rapid cellular responses to larvae appear to tip the balance of the host-parasite relationship in favour of the host, preventing severe immune-physiological impacts of the more invasive adults.

Immunological, transcriptomic, genomic and proteomic evidence suggests pathological impacts occur in susceptible hosts through modulation of host immunity and physiology via pharmacologically active molecules. Co-evolutionary and farming selection pressures may have incurred preference of Atlantic salmon as a host for Lsal reflected in their interactome.

Here we review host-parasite interactions at the primary attachment/feeding site, and the complex life-stage dependent molecular mechanisms employed to subvert host physiology and immune responses.