scholarly journals Genomic Characterization of a New Biofilm-Forming and Adhesive ST398 Human-Adapted MSSA Lineage Causing Septic Knee Arthritis Following Surgical Reconstruction

2021 ◽  
Vol 9 (2) ◽  
pp. 305
Author(s):  
Viviana Cafiso ◽  
Flavia Lo Verde ◽  
Alessandra Zega ◽  
Giuseppe Pigola ◽  
Roberto Rostagno ◽  
...  

Methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen commonly found in bone and joint infections, including septic arthritis. S. aureus virulence and the frailty of affected patients can cause several complications; a prompt and specific antibiotic treatment can positively affect the outcome of patients. We carried out an in-depth genomic characterization by Illumina whole genome sequencing and bioinformatics of two biofilm-producing M1 and M2 ST398 MSSA causing septic knee arthritis not-responding to antimicrobial therapy. The strains were characterized for antibiotic resistance, biofilm and adhesive properties as well as genomics, single nucleotide polymorphism phylogeny, resistomics and virulomics. Our results showed that M1 and M2 MSSA were ST398-t1451-agrI-Cap5, susceptible to cefoxitin and resistant to erythromycin and clindamycin, traits consistent with the lack of the SCCmec-locus and the presence of the sole blaZ and ermT. Furthermore, M1 and M2 were biofilm-producing and largely potentially adhesive strains, as indicated by the adhesion gene profile. Our data characterized a new human-adapted ST398 MSSA lineage, representing a “fusion” between the human-animal independent ST398 and the Livestock Associated (LA) ST398 lineages, forming biofilm and genomically predicted high adhesive, characterized by different genomic adaptation conferring a great ability to adhere to the host’s extracellular matrix causing septic knee arthritis.

Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2073
Author(s):  
Nicolás Galarce ◽  
Beatriz Escobar ◽  
Eduard Martínez ◽  
Natalia Alvarado ◽  
Gabriela Peralta ◽  
...  

Canine brucellosis caused by Brucella canis is a zoonotic disease that causes reproductive alterations in dogs, such as infertility, abortion, and epididymitis. This pathogen is especially prevalent in South America, and due to the lack of official control programs and the growing trend of adopting dogs it constitutes a public health risk that must be addressed. The aim of this study was to determine the prevalence of B. canis infection in kennel, shelter, and household dogs and to characterize the genomic properties of circulating strains, including ure and virB operons and omp25/31 genes. Samples from 771 dogs were obtained, and the infection was detected by blood culture and/or serology in 7.0% of the animals. The complete ure and virB operons and the omp25/31 genes were detected. Interestingly, we found different single-nucleotide polymorphisms (SNPs) in some of the analyzed genes, which could mean a change in the fitness or virulence of these strains. This study provides further evidence about dogs as a source of B. canis strains that can infect people. This also highlights the need to implement official control programs, including the mandatory testing of dogs, especially stray dogs, before adoption.


2016 ◽  
Author(s):  
Greg Fedewa ◽  
Sheli R. Radoshitzky ◽  
Xiǎolì Chī ◽  
Lián Dǒngb ◽  
Melissa Spear ◽  
...  

ABSTRACTEbola virus disease (EVD) is a viral hemorrhagic fever with a high case-fatality rate in humans. EVD is caused by four members of the filoviral genusEbolavirus, with Ebola virus (EBOV) being the most notorious one. Although bats are discussed as potential ebolavirus reservoirs, limited data actually support this hypothesis. Glycoprotein 2 (GP2) of reptarenaviruses, known to infect only boa constrictors and pythons, are similar in sequence and structure to ebolaviral glycoprotein 2 (GP2), suggesting that EBOV may be able to infect snake cells. We therefore serially passaged EBOV and a distantly related filovirus, Marburg virus (MARV), in the boa constrictor kidney cell line, JK, and characterized viral growth and mutational frequency by sequencing. We observed that EBOV efficiently infected and replicated in JK cells, but MARV did not. In contrast to most cell lines, EBOV infected JK cells did not result in obvious cytopathic effect (CPE). Genomic characterization of serial-passaged EBOV in JK cells revealed that genomic adaptation was not required for infection. Deep sequencing coverage (>10,000x) demonstrated the existence of only a single non-synonymous variant (EBOV glycoprotein precursor preGP T544I) of unknown significance within the viral population that exhibited a shift in frequency of at least 10% over six passages. Our data suggest that boid snake derived cells are competent for filovirus infection without appreciable genomic adaptation; that cellular filovirus infection without CPE may be more common than currently appreciated; and that there may be significant differences between the natural host spectra of ebolaviruses and marburgviruses.IMPORTANCEEbola virus (EBOV) causes a high case-fatality form of viral hemorrhagic fever. The natural reservoir of EBOV remains unknown. EBOV is distantly related to Marburg virus (MARV), which has been found in bats in the wild. The glycoprotein of a reptarenavirus known to infect boid snakes (pythons and boas) shows similarity in sequence and structure to these viruses, suggesting that EBOV and MARV may be able to infect and replicate in snake cells. We demonstrate that JK, a boa constrictor cell line, does not support MARV infection, but does support EBOV infection without causing overt cytopathic effect or the need for appreciable adaptation. These findings suggest different filoviruses may have a more diverse natural host spectra than previously thought.


2020 ◽  
Author(s):  
Carolina M Voloch ◽  
Ronaldo da Silva F ◽  
Luiz G P de Almeida ◽  
Cynthia C Cardoso ◽  
Otavio J. Brustolini ◽  
...  

AbstractIn this study, we report the sequencing of 180 new viral genomes obtained from different municipalities of the state of Rio de Janeiro from April to December 2020. We identified a novel lineage of SARS-CoV-2, originated from B.1.1.28, distinguished by five single-nucleotide variants (SNVs): C100U, C28253U, G28628U, G28975U, and C29754U. The SNV G23012A (E484K), in the receptor-binding domain of Spike protein, was widely spread across the samples. This mutation was previously associated with escape from neutralizing antibodies against SARS-CoV-2. This novel lineage emerged in late July being first detected by us in late October and still mainly restricted to the capital of the state. However, as observed for other strains it can be rapidly spread in the state. The significant increase in the frequency of this lineage raises concerns about public health management and continuous need for genomic surveillance during the second wave of infections.Article Summary LineWe identified a novel circulating lineage of SARS-CoV-2 in the state of Rio de Janeiro Brazil originated from B.1.1.28 lineage.


Planta Medica ◽  
2011 ◽  
Vol 77 (12) ◽  
Author(s):  
AS Lima ◽  
B Lukas ◽  
J Novak ◽  
AC Figueiredo ◽  
LG Pedro ◽  
...  

2020 ◽  
Vol 20 (7) ◽  
pp. 490-500 ◽  
Author(s):  
Justin S. Becker ◽  
Amir T. Fathi

The genomic characterization of acute myeloid leukemia (AML) by DNA sequencing has illuminated subclasses of the disease, with distinct driver mutations, that might be responsive to targeted therapies. Approximately 15-23% of AML genomes harbor mutations in one of two isoforms of isocitrate dehydrogenase (IDH1 or IDH2). These enzymes are constitutive mediators of basic cellular metabolism, but their mutated forms in cancer synthesize an abnormal metabolite, 2- hydroxyglutarate, that in turn acts as a competitive inhibitor of multiple gene regulatory enzymes. As a result, leukemic IDH mutations cause changes in genome structure and gene activity, culminating in an arrest of normal myeloid differentiation. These discoveries have motivated the development of a new class of selective small molecules with the ability to inhibit the mutant IDH enzymes while sparing normal cellular metabolism. These agents have shown promising anti-leukemic activity in animal models and early clinical trials, and are now entering Phase 3 study. This review will focus on the growing preclinical and clinical data evaluating IDH inhibitors for the treatment of IDH-mutated AML. These data suggest that inducing cellular differentiation is central to the mechanism of clinical efficacy for IDH inhibitors, while also mediating toxicity for patients who experience IDH Differentiation Syndrome. Ongoing trials are studying the efficacy of IDH inhibitors in combination with other AML therapies, both to evaluate potential synergistic combinations as well as to identify the appropriate place for IDH inhibitors within existing standard-of-care regimens.


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