Genomic characterization of genes encoding histone acetylation modulator proteins identifies therapeutic targets for cancer treatment

Cyanobacteria are one of the dominant autotrophs in tropical freshwater communities, yet phages infecting them remain poorly characterized. Here we present the characterization of cyanophage S-SRP02, isolated from a tropical freshwater lake in Singapore, which infects Synechococcus sp. Strain SR-C1 isolated from the same lake. S-SRP02 represents a new evolutionary lineage of cyanophage. Out of 47 open reading frames (ORFs), only 20 ORFs share homology with genes encoding proteins of known function. There is lack of auxiliary metabolic genes which was commonly found as core genes in marine cyanopodoviruses. S-SRP02 also harbors unique structural genes highly divergent from other cultured phages. Phylogenetic analysis and viral proteomic tree further demonstrate the divergence of S-SRP02 from other sequenced phage isolates. Nonetheless, S-SRP02 shares synteny with phage genes of uncultured phages obtained from the Mediterranean Sea deep chlorophyll maximum fosmids, indicating the ecological importance of S-SRP02 and its related viruses. This is further supported by metagenomic mapping of environmental viral metagenomic reads onto the S-SRP02 genome.

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Faculty Opinions recommendation of Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725812637.793510046 ◽

2015 ◽

Author(s):

Matthias Preusser

Keyword(s):

Brain Metastases ◽

Therapeutic Targets ◽

Genomic Characterization ◽

Branched Evolution

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Comprehensive genomic characterization of hepatocellular carcinoma to reveal novel therapeutic targets.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.e15643 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. e15643-e15643

Author(s):

Yuewei Zhang ◽

Yan Ding

Keyword(s):

Hepatocellular Carcinoma ◽

Therapeutic Targets ◽

Genomic Characterization ◽

Novel Therapeutic

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Rhabdomyosarcoma, Ewing Sarcoma, and Other Round Cell Sarcomas

Journal of Clinical Oncology ◽

10.1200/jco.2017.74.7402 ◽

2018 ◽

Vol 36 (2) ◽

pp. 168-179 ◽

Cited By ~ 38

Author(s):

Alberto S. Pappo ◽

Uta Dirksen

Keyword(s):

Ewing Sarcoma ◽

Therapeutic Targets ◽

Genomic Rearrangements ◽

Round Cell ◽

Tumor Subtypes ◽

Specific Tumor ◽

Genomic Characterization ◽

Round Cell Tumors ◽

Made In

Several recent advances have been made in the diagnosis and therapy of malignant small round cell tumors that affect children, particularly in rhabdomyosarcoma, Ewing sarcoma, and other round cell sarcomas. These advances have provided new insights into the pathologic, histologic, and genomic characterization of specific tumor subtypes, which has led to the identification of novel therapeutic targets and improved stratification of risk. This has, in turn, led to improved efficacy in clinical trials of new drug combinations, thereby increasing the survival of patients with newly diagnosed and refractory or recurrent round cell sarcomas. Here, we review the progress that has been made using genomics to identify novel pathologic genomic rearrangements, as well as therapeutic targets. We also describe how clinical and molecular factors have helped refine risk stratification and therapies that have led to improved clinical outcomes in patients with round cell sarcomas.

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Biochemical and Genomic Characterization of the Cypermethrin-Degrading and Biosurfactant-Producing Bacterial Strains Isolated from Marine Sediments of the Chilean Northern Patagonia

Marine Drugs ◽

10.3390/md18050252 ◽

2020 ◽

Vol 18 (5) ◽

pp. 252 ◽

Cited By ~ 2

Author(s):

Patricia Aguila-Torres ◽

Jonathan Maldonado ◽

Alexis Gaete ◽

Jaime Figueroa ◽

Alex González ◽

...

Keyword(s):

Marine Sediments ◽

Enrichment Culture ◽

Extreme Environments ◽

Environmental Damage ◽

Bacterial Strains ◽

Culture Techniques ◽

Northern Patagonia ◽

Genes Encoding ◽

Genomic Characterization

Pesticides cause severe environmental damage to marine ecosystems. In the last ten years, cypermethrin has been extensively used as an antiparasitic pesticide in the salmon farming industry located in Northern Patagonia. The objective of this study was the biochemical and genomic characterization of cypermethrin-degrading and biosurfactant-producing bacterial strains isolated from cypermethrin-contaminated marine sediment samples collected in southern Chile (MS). Eleven strains were isolated by cypermethrin enrichment culture techniques and were identified by 16S rDNA gene sequencing analyses. The highest growth rate on cypermethrin was observed in four isolates (MS13, MS15a, MS16, and MS19) that also exhibited high levels of biosurfactant production. Genome sequence analyses of these isolates revealed the presence of genes encoding components of bacterial secondary metabolism, and the enzymes esterase, pyrethroid hydrolase, and laccase, which have been associated with different biodegradation pathways of cypermethrin. These novel cypermethrin-degrading and biosurfactant-producing bacterial isolates have a biotechnological potential for biodegradation of cypermethrin-contaminated marine sediments, and their genomes contribute to the understanding of microbial lifestyles in these extreme environments.

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Isolation of New Stenotrophomonas Bacteriophages and Genomic Characterization of Temperate Phage S1

Applied and Environmental Microbiology ◽

10.1128/aem.01709-08 ◽

2008 ◽

Vol 74 (24) ◽

pp. 7552-7560 ◽

Cited By ~ 21

Author(s):

Pilar García ◽

Cristina Monjardín ◽

Rebeca Martín ◽

Carmen Madera ◽

Nora Soberón ◽

...

Keyword(s):

Burst Size ◽

Gene Clusters ◽

Open Reading Frames ◽

Virus Particles ◽

Bacterial Titer ◽

Genes Encoding ◽

Replication Gene ◽

Genomic Characterization ◽

Phosphoadenosine Phosphosulfate

ABSTRACT Twenty-two phages that infect Stenotrophomonas species were isolated through sewage enrichment and prophage induction. Of them, S1, S3, and S4 were selected due to their wide host ranges compared to those of the other phages. S1 and S4 are temperate siphoviruses, while S3 is a virulent myovirus. The genomes of S3 and S4, about 33 and 200 kb, were resistant to restriction digestion. The lytic cycles lasted 30 min for S3 and about 75 min for S1 and S4. The burst size for S3 was 100 virions/cell, while S1 and S4 produced about 75 virus particles/cell. The frequency of bacteriophage-insensitive host mutants, calculated by dividing the number of surviving colonies by the bacterial titer of a parallel, uninfected culture, ranged between 10−5 and 10−6 for S3 and 10−3 and 10−4 for S1 and S4. The 40,287-bp genome of S1 contains 48 open reading frames (ORFs) and 12-bp 5′ protruding cohesive ends. By using a combination of bioinformatics and experimental evidence, functions were ascribed to 21 ORFs. The morphogenetic and lysis modules are well-conserved, but no lysis-lysogeny switch or DNA replication gene clusters were recognized. Two major clusters of genes with respect to transcriptional orientation were observed. Interspersed among them were lysogenic conversion genes encoding phosphoadenosine phosphosulfate reductase and GspM, a protein involved in the general secretion system II. The attP site of S1 may be located within a gene that presents over 75% homology to a Stenotrophomonas chromosomal determinant.

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In-Depth Genomic Characterization of a Meropenem-nonsusceptible Pseudomonas otitidis Strain Contaminating Chicken Carcass

Acta Scientiae Veterinariae ◽

10.22456/1679-9216.103176 ◽

2020 ◽

Vol 48 ◽

Author(s):

Tatiana Regina Vieira ◽

Gustavo Enck Sambrano ◽

Núbia Michelle Vieira da Silva ◽

Priscylla Carvalho Vasconcelos ◽

Esther Ferraza Cavinatto de Oliveira ◽

...

Keyword(s):

Public Health ◽

Antimicrobial Resistance ◽

Resistant Bacteria ◽

Beta Lactamase ◽

Food Animal ◽

Chicken Carcass ◽

Pseudomonas Species ◽

Genes Encoding ◽

Genomic Characterization

Background: The indiscriminate use of antibiotics in food-animal production has a major impact on public health, particularly in terms of contributing to the emergence and dissemination of antimicrobial resistant bacteria in the food-animal production chain. Although Pseudomonas species are recognized as important spoilage organisms in foodstuff, they are also known as opportunistic pathogens associated with hospital-acquired infections. Furthermore, Pseudomonas can play a role as potential reservoirs of antimicrobial resistance genes, which may be horizontally transferred to other bacteria. Considering that cephalosporins (3rd and higher generations) and carbapenems are critically important beta-lactam antimicrobials in human medicine, this study reports the occurrence and genomic characterization of a meropenem-nonsusceptible Pseudomonas otitidis strain recovered from a chicken carcass in Brazil.Materials, Methods & Results: During the years 2018-2019, 72 frozen chicken carcasses were purchased on the retail market from different regions in Brazil. Aliquots from individual carcass rinses were screened for Extended Spectrum Beta-lactamase (ESBL)-producing bacteria in MacConkey agar supplemented with 1mg.L-1 cefotaxime. Phenotypically resistant isolates were further tested for resistance to other antimicrobials and confirmed as ESBL-producers by means of disk-diffusion method using Müller-Hinton agar. Only one meropenen-nonsusceptible isolate was detected and submitted to whole genome sequencing (WGS) in Illumina Miseq. The strain was identified as Pseudomonas otitidis by local alignment of the 16S rRNA sequence using BLASTn and confirmed by Average Nucleotide Identity (ANI) analysis using JspeciesWS database. Genes encoding for antimicrobial resistance were detected by means of Resfinder and Comprehensive Antibiotic Resistance Database (CARD) databases. The phenotypic non-susceptibility to meropenen was attributed to the gene blaPOM-1. A total of 192 different genes encoding for quorum sensing system, antiphagocytosis, iron uptake, efflux pump, endotoxin and toxin, adherence, and secretion systems were detected by means of Virulence Factor Database (VFDB). Pseudomonas otitidis-pan genome was built using Roary-rapid large-scale prokaryote pan genome analysis using the present strain (K_25) and other two P. otitidis genomes (PAM-1, DSM 17224) publicly available at the NCBI. The core genome analysis of the two human strains resulted in similar percentages.Discussion: Carbapenems are critically important drugs for human health and bacterial strains resistant to these antimicrobials pose a public health problem. The blaPOM-1 gene harbored by the Pseudomonas otitidis K_25 strain encodes a metallo-beta-lactamase (MBL) conferring resistance to carbapenems. Pseudomonas otitidis was the first confirmed pathogenic Pseudomonas species expressing MBL constitutively in the absence of inducible beta-lactamase genes. Furthermore, the several virulence genes associated with the capacity of the P. otitidis K_25 to colonize, evade the immune system and cause lesions in the human host confirm this strain as a potential opportunistic pathogen contaminating foodstuff. These reinforce the need to address antimicrobial resistance in a One Health perspective, in which resistant bacteria and resistance determinants circulate among environment, animals and humans.

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