Publications by authors named "Marina Muňoz"

97 Publications

Phylogenomic Evidence of Reinfection and Persistence of SARS-CoV-2: First Report from Colombia.

Vaccines (Basel) 2021 Mar 19;9(3). Epub 2021 Mar 19.

Icahn School of Medicine at Mount Sinai, New York, NY 10001, USA.

The continuing evolution of SARS-CoV-2 and the emergence of novel variants have raised concerns about possible reinfection events and potential changes in the coronavirus disease 2019 (COVID-19) transmission dynamics. Utilizing Oxford Nanopore technologies, we sequenced paired samples of three patients with positive RT-PCR results in a 1-2-month window period, and subsequent phylogenetics and genetic polymorphism analysis of these genomes was performed. Herein, we report, for the first time, genomic evidence of one case of reinfection in Colombia, exhibiting different SARS-CoV-2 lineage classifications between samples (B.1 and B.1.1.269). Furthermore, we report two cases of possible viral persistence, highlighting the importance of deepening our understanding on the evolutionary intra-host traits of this virus throughout different timeframes of disease progression. These results emphasize the relevance of genomic surveillance as a tool for understanding SARS-CoV-2 infection dynamics, and how this may translate effectively to future control and mitigations efforts, such as the national vaccination program.
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http://dx.doi.org/10.3390/vaccines9030282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003345PMC
March 2021

Kidney Transplantation in Small Children: Association Between Body Weight and Outcome - A Report From the ESPN/ERA-EDTA Registry.

Transplantation 2021 Mar 26. Epub 2021 Mar 26.

Division of Pediatric Nephrology and Gastroenterology, Medical University Vienna, Austria ESPN/ERA-EDTA Registry, Amsterdam UMC, University of Amsterdam, Department of Medical Informatics, Amsterdam Public Health research institute, Meibergdreef 9, Amsterdam, the Netherlands; Department of Pediatric Nephrology, University Medical Center Ljubljana, Slovenia; Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Norway; Children's Medical Center, Landspitali-The National University Hospital of Iceland, and Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; Karolinska Institutet- Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Pediatrics, Medical University Graz, Graz, Austria; Department of Pediatric Nephrology and Transplantation, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Pediatric Nephrology, Erasmus MC- Sophia Children's Hospital, Rotterdam, the Netherlands; Nephrology Unit, University Children's Hospital, Zürich, Switzerland; S.C. Nefrologia e Dialisi, Azienda Ospefaliero-Universitaria di Perugia, Perugia, Italy; Department of Kidney Transplantation, Russian Children's Federal Clinical Hospital of Pirogov Russian National Research Medical University, Moscow, Russia; Department of Pediatric Nephrology, University Hospital Vall d'Hebron, Barcelona, Spain; Faculty of Medicine Seyhan, Adana Dr. Turgut Noyan Training and Research Center, Department of Pediatric Nephrology, Başkent University, Adana, Turkey; Department of Pediatric Nephrology, Hannover Medical School, Hannover, Germany; 1st Pediatric Department, Aristotle University of Thessaloniki, Thessaloniki, Greece; 1st Department of Pediatrics, Semmelweis University Budapest, Budapest, Hungary; Pediatric Nephrology Unit, University Hospital of Nantes, Nantes, France; Department ofNephrology, Kidney Transplantation & Hypertension, The Children's Memorial Health Institute, Warsaw, Poland; Department of Nephrology, University Children's hospital, Belgrade, Serbia; Department of Pediatrics, University Hospital Motol, 2nd Medical Faculty and Faculty of Medicine in Plzen, Charles University Prague and Biomedical Centre, Prague, Czech Republic; Department of Pediatric Nephrology, Evelina London Children's Hospital, Guy's and St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Division of Pediatrics, Department of Medicine, University of Udine, Udine, Italy; Pediatric Nephrology Unit, Bordeaux University Hospital, Bordeaux, France; Amsterdam UMC, University of Amsterdam, Department of Pediatric Nephrology, Emma Children's Hospital, Academic Medical Center, Meibergdreef 9, Amsterdam, the Netherlands.

Background: Many centers accept a minimum body weight of 10 kg as threshold for kidney transplantation (Tx) in children. As solid evidence for clinical outcomes in multinational studies is lacking, we evaluated practices and outcomes in European children weighing below 10 kg at Tx.

Methods: Data were obtained from the ESPN/ERA-EDTA Registry on all children who started kidney replacement therapy (KRT) at <2.5 years of age and received a Tx between 2000 and 2016. Weight at Tx was categorized (<10 kg versus ≥10 kg) and Cox regression analysis was used to evaluate its association with graft survival.

Results: One hundred of the 601 children received a Tx below a weight of 10 kg during the study period. Primary renal disease groups were equal, but Tx <10 kg patients had lower pre-Tx weight gain per year (0.2 kg versus 2.1 kg; p<0.001) and had a higher preemptive Tx rate (23% versus 7%; p<0.001). No differences were found for posttransplant estimated glomerular filtration rates (eGFR) trajectories (p=0.23).The graft failure risk was higher in Tx <10 kg patients at 1 year (graft survival: 90% versus 95%; aHR: 3.84, 95% CI: 1.24-11.84), but not at 5 years (aHR: 1.71, 95% CI: 0.68-4.30).

Conclusions: Despite a lower 1-year graft survival rate, graft function and survival at 5 years were identical in Tx <10 kg patients when compared with Tx ≥10 kg patients. Our results suggest that early transplantation should be offered to a carefully selected group of patients weighing <10 kg.
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http://dx.doi.org/10.1097/TP.0000000000003771DOI Listing
March 2021

Gut microbiota profiles in diarrheic patients with co-occurrence of Clostridioides difficile and Blastocystis.

PLoS One 2021 16;16(3):e0248185. Epub 2021 Mar 16.

Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia.

Blastocystis and Clostridioides difficile co-occurrence is considered a rare event since the colonization by Blastocystis is prevented under a decrease in beneficial bacteria in the microbiota when there is C. difficile infection (CDI). This scenario has been reported once, but no information on the gut microbiota profiling is available. The present study is motivated by knowing which members of the microbiota can be found in this rare scenario and how this co-occurrence may impact the abundance of other bacteria, eukaryotes or archaea present in the gut microbiota. This study aimed to describe the bacterial and eukaryotic communities using amplicon-based sequencing of the 16S- and 18S-rRNA regions of three patient groups: (1) Blastocystis and C. difficile infection (B+/C+, n = 31), (2) C. difficile infection only (B-/C+, n = 44), and (3) without Blastocystis or C. difficile (B-/C-, n = 40). Blastocystis was subtyped using amplicon-based sequencing of the 18S-rRNA gene, revealing circulation of subtypes ST1 (43.4%), ST3 (35.85%) and ST5 (20.75%) among the study population. We found that B+/C+ patients had a higher abundance of some beneficial bacteria (such as butyrate producers or bacteria with anti-inflammatory properties) compared with non-Blastocystis-colonized patients, which may suggest a shift towards an increase in beneficial bacteria when Blastocystis colonizes patients with CDI. Regarding eukaryotic communities, statistical differences in the abundance of some eukaryotic genera between the study groups were not observed. Thus, this study provides preliminary descriptive information of a potential microbiota profiling of differential presence by Blastocystis and C. difficile.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248185PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963057PMC
March 2021

Relationship between soluble urokinase-type plasminogen activator receptor and serum biomarkers of endothelial activation in patients with idiopathic nephrotic syndrome.

Clin Kidney J 2021 Feb 17;14(2):543-549. Epub 2020 Jan 17.

Servicio de Nefrología, Hospital Universitario Arnau de Vilanova, Lleida, Spain.

Background: Serum levels of soluble urokinase-type plasminogen activator receptor (suPAR) are high in some patients with idiopathic nephrotic syndrome (INS). Given that suPAR constitutes a predictor of vascular disease and has been associated with endothelial dysfunction, we hypothesized that suPAR levels are related to endothelial activation or dysfunction in INS patients. The aims of this study were to evaluate the relationship between serum concentrations of endothelial biomarkers and suPAR in patients with different histological patterns of INS and healthy controls, and to determine the demographic, clinical and biochemical characteristics of INS patients that influence suPAR serum levels.

Methods: This observational, cross-sectional study included patients with INS, diagnosed with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) or membranous nephropathy (MN) by renal biopsy. Patient demographic, clinical and biochemical characteristics were recorded and blood samples were obtained at the time of diagnosis. Measurements of suPAR and endothelial molecules via serum levels were performed using Enzyme-Linked ImmunoSorbent Assay kits.

Results: Patients with nephrotic syndrome ( = 152) caused by FSGS, MCD or MN had increased circulating levels of endothelial markers. suPAR levels positively correlated with age and the serum levels of almost all endothelial markers. Generally, endothelial cell molecules positively correlated with each other. suPAR levels were not associated with the histopathological pattern of INS.

Conclusions: In patients with INS secondary to FSGS, MCD and NM, circulating levels of suPAR are independent of the primary renal disease, and significantly associated with age, glomerular filtration rate and the levels of various endothelial markers.
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http://dx.doi.org/10.1093/ckj/sfz173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886542PMC
February 2021

Characterizing SARS-CoV-2 genome diversity circulating in South American countries: Signatures of potentially emergent lineages?

Int J Infect Dis 2021 Feb 20;105:329-332. Epub 2021 Feb 20.

Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia. Electronic address:

Objectives: To evaluate the genomic diversity and geographic distribution of SARS-CoV-2 lineages in South America.

Methods: SARS-CoV-2 lineages from a public dataset of 5583 South American genome assemblies were analyzed. Polymorphisms in the main open reading frames were identified and compared to those in the main lineages of epidemiological concern: B.1.1.7 (UK) and B.1.351 (South Africa).

Results: Across 16 South American countries, 169 lineages were identified; major lineage B had the greatest diversity and broadest geographic distribution. Seventeen predominant lineages were analyzed revealing 2 dominant lineages of concern: P.1 (Brazilian variant) and B.1.1.7 with 94 and 28 genomes, respectively, both with 33 polymorphisms (other lineages displayed ≤24 polymorphisms). A high number of polymorphisms were detected with a limited number of common variable positions, in common with the profile of the main lineages of epidemiological concern.

Conclusions: The ever-increasing genetic diversity of SARS-CoV-2 continues to lead to novel lineage emergence. Various variants and lineages are now present across South America, dominated by major lineage B. The circulation of P.1 and B.1.1.7 and the high number of polymorphisms highlight the importance of genomic surveillance to determine introduction events, identify transmission chains, trace emergence, and implement prevention, vaccination and control strategies.
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http://dx.doi.org/10.1016/j.ijid.2021.02.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895695PMC
February 2021

Lack of clinical significance for molecular detection of respiratory viruses in bronchoalveolar lavage samples.

J Med Virol 2021 Feb 2. Epub 2021 Feb 2.

Department of Microbiology, University Hospital 12 de Octubre, Madrid, Spain.

The clinical significance of molecular detection of respiratory viruses in bronchoalveolar lavage (BAL) samples is poorly defined. We performed an observational retrospective study including all patients who underwent a BAL procedure in our institution, regardless of the reason for bronchoscopy, from January 2015 to December 2018. Respiratory viruses were detected by real-time polymerase chain reaction with a commercial multiplex panel, and a cell culture was performed to detect cytomegalovirus and herpes simplex virus. Positive results were correlated with clinical symptoms and patients' characteristics. Of 540 BAL samples analyzed, 113 (20.9%) were positive for any respiratory virus. Viral detection was significantly associated with respiratory symptoms (83.2% vs. 68.9%, p = .004) and radiological infiltrates (67.3% vs. 52.2%, p = .006). The most frequent viruses detected were rhinovirus (42/113, 37.2%), influenza virus (20/113, 17.7%), and parainfluenza virus (PIV) (16/113, 14.2%). Respiratory pathogens codetections were found in 51/113 (45.1%) BAL samples, including more than one virus (16/51, 31.4%), fungi (8/51, 15.7%), and bacteria (9/51, 17.6%). Viral detection was significantly higher in immunocompromised patients (26.5% vs. 16.9%; p = .022). PIV and human metapneumovirus were mostly observed in lung (50.0%, 8/16) and hemopoietic transplant recipients (25%, 2/8), respectively, with clinical repercussions. Our data underline that molecular diagnosis allows identification of viral agents as the etiology of respiratory infections; however, the high frequency of codetections hinders identification of the agent responsible for the current respiratory symptomatology. Immunocompromised patients are the target population in whom to investigate the presence of respiratory viruses in their BAL samples.
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http://dx.doi.org/10.1002/jmv.26843DOI Listing
February 2021

Home Albumin Infusion Therapy, Another Alternative Treatment in Patients With Congenital Nephrotic Syndrome of the Finnish Type.

Front Pediatr 2020 14;8:614535. Epub 2021 Jan 14.

Pediatric Nephrology Department, Vall d'Hebron University Hospital, Barcelona, Spain.

Congenital nephrotic syndrome of the Finnish type (CNF) is a rare, severe glomerular disease caused by mutations in the NPHS1 gene, which codes for nephrin. It is characterised by massive proteinuria and severe edoema. Progression to end-stage kidney failure occurs during early childhood and the only curative treatment is kidney transplantation. Nowadays, patients need aggressive medical treatment, which includes daily albumin infusions (for months) until they get clinical stability to receive transplant. In our paediatric hospital, we implemented a multidisciplinary program for the home infusion of albumin with outpatient follow-up. The aim of the study was to assess the safety and efficacy of this program for the first four years of its implementation. Retrospective observational study of CNF paediatric patients treated with home albumin infusion therapy from March 2014 to July 2018 at a tertiary care paediatric hospital. Information on albumin administration was obtained from the electronic prescription assistance program and details on clinical and care-related variables from the hospital's electronic information systems. Four patients with CNF received albumin infusions for 18, 21, 22 months, and 3 years. The treatment was safe, and the complication rates were to be expected considering the severity of disease. Patients required a median of two hospital admissions a year (19 in total); 47% due to catheter-related complications, but there were just three catheter infections. In our experience, home albumin infusion therapy is safe and effective and helps to improve children health and quality of life.
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http://dx.doi.org/10.3389/fped.2020.614535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841340PMC
January 2021

Will the emergent SARS-CoV2 B.1.1.7 lineage affect molecular diagnosis of COVID-19?

J Med Virol 2021 May 9;93(5):2566-2568. Epub 2021 Feb 9.

Department of Pathology, Molecular and Cell-Based Medicine, Laboratory of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

As the coronavirus disease 2019 pandemic keep tackling global public health systems worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) genome keeps mutating. In that regard, the recent emergence of the B.1.1.7 lineage in the UK has called the attention of global authorities. One point of concern is that if this lineage can be detected by traditional molecular schemes for SARS-CoV-2 detection. Herein, we showed that this lineage does not affect the Berlin-Charité protocol but can challenge the available commercial kits directed to the Spike (S) gene. All efforts should be made to continue to monitor SARS-CoV-2 genomes for potential variants that can impair diagnostic testing and lead to false negative results.
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http://dx.doi.org/10.1002/jmv.26823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013853PMC
May 2021

Microbial Communities' Characterization in Urban Recreational Surface Waters Using Next Generation Sequencing.

Microb Ecol 2021 Jan 3. Epub 2021 Jan 3.

Grupo de Investigaciones Microbiológicas- UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, 110221, Colombia.

Microbial communities in surface waters used for recreational purposes are indicators of contamination and risk of contact with human pathogens. Hence, monitoring microbial communities in recreational waters is important for potential public health threats to humans. Such monitoring is rare in Colombia, even in its capital, Bogotá, the most populous city in the country. This city encompasses metropolitan and linear parks with recreational water bodies that are used frequently by the public, and the presence of pathogens can compromise the health of the citizens. Therefore, we examined the bacterial, and eukaryotic communities in urban recreational lakes (URL) in four metropolitan parks in Bogotá, Colombia. Samples from four metropolitan parks (Los Novios, Simon Bolivar, El Tunal, and Timiza) and one stream contaminated with sewage from a linear park (El Virrey) were collected. We used amplicon next-generation sequencing of the 16S-rRNA gene and 18S-rRNA gene to characterize microbial communities followed by bioinformatics analyses. In addition, general water quality parameters-pH, hardness, acidity, alkalinity, dissolved oxygen, and nitrites-were recorded using a commercial kit. Genera of pathogens, including Legionella, Pseudomonas, Mycobacterium, Candida, and Naegleria, were found in lake waters. The stream El Virrey was, however, the only surface water that showed an abundance of fecal bacteria, often associated with low oxygen concentrations. All water bodies showed a predominance of fungal phyla, except for the lake at Timiza. This lake showed the highest pH, and its ecological dynamics are likely different from other water bodies. Likewise, some URLs displayed a greater abundance of cyanobacteria, including toxin-producing species. Algal genera associated with eutrophication were predominant among primary producing microorganisms. This study shows for the first time the description of the bacterial and eukaryotic communities of some URLs and a stream in Bogotá. The URLs and the stream harbored various pathogens that might pose a risk to the citizen's health.
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http://dx.doi.org/10.1007/s00248-020-01649-9DOI Listing
January 2021

Linear Growth in Pediatric Kidney Transplant Population.

Front Pediatr 2020 8;8:569616. Epub 2020 Dec 8.

Department of Pediatric Nephrology, University Hospital Vall d'Hebron, Barcelona, Spain.

Growth retardation is one of the main complications of chronic kidney disease (CKD) in children and induces a negative impact on quality of life. Retrospective analysis of all consecutive patients younger than 18 years old who received a first KT in our center between 2008 and 2018. 95 first KT recipients, median age at KT of 7.83 years. At the time of KT, 65.52% of males and 54.05% females showed normal height. After transplantation, linear growth improved from -1.53 at transplant to -1.37 SDS height at the last visit. We detected a different linear growth pattern according to patient age at KT. Children younger than 3 years old exhibited the most significant growth retardation at baseline and the greatest linear growth over time (-2.29 vs. -1.82 SDS height), whereas catch-up was not observed in older patients. Multivariate analysis showed that use of corticosteroids was negatively related to SDS height at 1 year after transplantation and final SDS height only was positively associated with SDS height at KT. 44.2 and 22.1% patients received rhGH treatment before and after KT. 71.88% patients reached adulthood with normal final height. In our study, pediatric KT recipients exhibited a normal height in more than half of cases at KT and in more than two thirds at the final adult height. Only children younger than 6 years old presented a relevant growth catch-up after KT. Treatment with rhGH was used before and after KT with significant improvement in height.
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http://dx.doi.org/10.3389/fped.2020.569616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752780PMC
December 2020

Comprehensive genome analyses of , a potential biomarker of homeostasis gut recovery.

Microb Genom 2020 12 18;6(12). Epub 2020 Nov 18.

Department of Biology, Texas A&M University, College Station, TX, 77843, USA.

is a Gram-positive and anaerobic bacterial species previously considered as uncultivable. Although little is known about this family member, its increased abundance has been reported in patients who have recovered from intestinal homeostasis after dysbiosis events. In this context, the aim of the present study was to take advantage of a massive culture protocol that allowed the recovery of extremely oxygen-sensitive species from faecal samples, which led to isolation of . Whole genome analyses of 11 . genomes revealed that this species has a highly conserved genome with 99.7 % 16S rRNA gene sequence similarity, average nucleotide polymorphism results >95, and 50.1 % of its coding potential being part of the core genome. Despite this, the variable portion of its genome was informative enough to reveal the existence of three lineages (lineage-I including isolates from Chile and France, lineage-II from South Korea and Finland, and lineage-III from China and one isolate from the USA) and evidence of some recombination signals. The identification of a cluster of orthologous groups revealed a high number of genes involved in metabolism, including amino acid and carbohydrate transport as well as energy production and conversion, which matches with the metabolic profile previously reported for microbiota from healthy individuals. Additionally, virulence factors and antimicrobial resistance genes were found (mainly in lineage-III), which could favour their survival during antibiotic-induced dysbiosis. These findings provide the basis of knowledge about the potential of as a bioindicator of intestinal homeostasis recovery and contribute to advancing the characterization of gut microbiota members with beneficial potential.
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http://dx.doi.org/10.1099/mgen.0.000476DOI Listing
December 2020

Species-dependent variation of the gut bacterial communities across Trypanosoma cruzi insect vectors.

PLoS One 2020 12;15(11):e0240916. Epub 2020 Nov 12.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia.

Triatomines (Hemiptera: Reduviidae) are the insect vectors of Trypanosoma cruzi, the causative agent of Chagas disease. The gut bacterial communities affect the development of T. cruzi inside the vector, making the characterization of its composition important in the understanding of infection development. We collected 54 triatomine bugs corresponding to four genera in different departments of Colombia. DNA extraction and PCR were performed to evaluate T. cruzi presence and to determine the discrete typing unit (DTU) of the parasite. PCR products of the bacterial 16S rRNA gene were pooled and sequenced. Resulting reads were denoised and QIIME 2 was used for the identification of amplicon sequence variants (ASVs). Diversity (alpha and beta diversity) and richness analyses, Circos plots, and principal component analysis (PCA) were also performed. The overall T. cruzi infection frequency was 75.9%, with TcI being the predominant DTU. Approximately 500,000 sequences were analyzed and 27 bacterial phyla were identified. The most abundant phyla were Proteobacteria (33.9%), Actinobacteria (32.4%), Firmicutes (19.6%), and Bacteroidetes (7.6%), which together accounted for over 90% of the gut communities identified in this study. Genera were identified for these main bacterial phyla, revealing the presence of important bacteria such as Rhodococcus, Serratia, and Wolbachia. The composition of bacterial phyla in the gut of the insects was significantly different between triatomine species, whereas no significant difference was seen between the state of T. cruzi infection. We suggest further investigation with the evaluation of additional variables and a larger sample size. To our knowledge, this study is the first characterization of the gut bacterial structure of the main triatomine genera in Colombia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240916PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660481PMC
December 2020

Genomic Diversification, Structural Plasticity, and Hybridization in .

Front Cell Infect Microbiol 2020 16;10:582192. Epub 2020 Oct 16.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia.

is an important species circulating in several Central and South American countries. Among species circulating in Brazil, Argentina and Colombia, has the highest genomic variability. However, genomic variability at the whole genome level has been only studied in Brazilian and Peruvian isolates; to date, no Colombian isolates have been studied. Considering that in Colombia, is a species with great clinical and therapeutic relevance, as well as the role of genetic variability in the epidemiology of leishmaniasis, we analyzed and evaluated intraspecific genomic variability of from Colombian and Bolivian isolates and compared them with Brazilian isolates. Twenty-one genomes were analyzed, six from Colombian patients, one from a Bolivian patient, and 14 Brazilian isolates downloaded from public databases. The results obtained of Phylogenomic analysis showed the existence of four well-supported clades, which evidenced intraspecific variability. The whole-genome analysis revealed structural variations in the somy, mainly in the Brazilian genomes (clade 1 and clade 3), low copy number variations, and a moderate number of single-nucleotide polymorphisms (SNPs) in all genomes analyzed. Interestingly, the genomes belonging to clades 2 and 3 from Colombia and Brazil, respectively, were characterized by low heterozygosity (~90% of SNP loci were homozygous) and regions suggestive of loss of heterozygosity (LOH). Additionally, we observed the drastic whole genome loss of heterozygosity and possible hybridization events in one genome belonging to clade 4. Unique/shared SNPs between and within the four clades were identified, revealing the importance of some of them in biological processes of . Our analyses demonstrate high genomic variability of in different regions of South America, mainly in Colombia and suggest that this species exhibits striking genomic diversity and a capacity of genomic hybridization; additionally, this is the first study to report whole-genome sequences of Colombian isolates.
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http://dx.doi.org/10.3389/fcimb.2020.582192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596589PMC
October 2020

Succinate dehydrogenase gene as a marker for studying genetic diversity.

Heliyon 2020 Nov 2;6(11):e05387. Epub 2020 Nov 2.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia.

has been reported as the most common eukaryotic microorganism residing in the intestines of both humans and animals, with a prevalence of up to 100% in some populations. Since this is a cryptic species, sequence polymorphism are the single strategy to analyses its genetic diversity, being traditionally used the analysis of gene sequence to determine alleles and subtypes (STs) for this species. This multicopy gene has shown high diversity among different STs, making necessary to explore other genes to assess intraspecific diversity. This study evaluated the use of a novel genetic marker, succinate dehydrogenase (), for the typing and evaluation of the genetic diversity and genetic population structure of . In total, 375 human fecal samples were collected and subjected to PCR, subtyped using the marker, and then the gene was amplified via PCR for 117 samples. We found some incongruences between tree topologies for both molecular markers. However, the clustering by ST previously established for was congruent in the concatenated sequence. showed lower reticulation (The origination of a lineage through the partial merging of two ancestor lineages) signals and better intra ST clustering ability. Clusters with geographical associations were observed intra ST. The genetic diversity was lower in the marker evaluated compared to that of the gene (nucleotide diversity = 0.03344 and 0.16986, respectively) and the sequences analyzed showed population expansion with genetic differentiation principally among STs. The gene was useful to explore interspecific diversity but together with the gene the resolution power to evaluate intra ST diversity was higher. These results showed the potential of the marker for studying the intra ST genetic diversity of related with geographical location and the inter ST diversity using the concatenated sequences.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609450PMC
November 2020

SARS-CoV-2 spread across the Colombian-Venezuelan border.

Infect Genet Evol 2020 12 4;86:104616. Epub 2020 Nov 4.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia.

Introduction: Venezuela and Colombia both adopted measures of containment early in response to the COVID-19 pandemic. However, Venezuela's ongoing humanitarian crisis has decimated its health care system, and forced millions of Venezuelans to flee through its porous border with Colombia. The extensive shared border, and illegal cross-border transit through improvised trails between the two countries are major challenges for public health authorities. We report the first SARS-CoV-2 genomes from Venezuela, and present a snapshot of the SARS-CoV-2 epidemiologic landscape in the Colombian-Venezuelan border region.

Methods: We sequenced and assembled viral genomes from total RNA extracted from nasopharyngeal (NP) clinical specimens using a custom reference-based analysis pipeline. Three assemblies obtained were subjected to typing using the Phylogenetic Assignment of Named Global Outbreak LINeages 'Pangolin' tool. A total of 376 publicly available SARS-CoV-2 genomes from South America were obtained from the GISAID database to perform comparative genomic analyses. Additionally, the Wuhan-1 strain was used as reference.

Results: We found that two of the SARS-CoV-2 genomes from Venezuela belonged to the B1 lineage, and the third to the B.1.13 lineage. We observed a point mutation in the Spike protein gene (D614G substitution), previously reported to be associated with increased infectivity, in all three Venezuelan genomes. Additionally, three mutations (R203K/G204R substitution) were present in the nucleocapsid (N) gene of one Venezuelan genome.

Conclusions: Genomic sequencing demonstrates similarity between SARS-CoV-2 lineages from Venezuela and viruses collected from patients in bordering areas in Colombia and from Brazil, consistent with cross-border transit despite administrative measures including lockdowns. The presence of mutations associated with increased infectivity in the 3 Venezuelan genomes we report and Colombian SARS-CoV-2 genomes from neighboring borders areas may pose additional challenges for control of SARS-CoV-2 spread in the complex epidemiological landscape in Latin American countries. Public health authorities should carefully follow the progress of the pandemic and its impact on displaced populations within the region.
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http://dx.doi.org/10.1016/j.meegid.2020.104616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609240PMC
December 2020

Microbiota characterization in Blastocystis-colonized and Blastocystis-free school-age children from Colombia.

Parasit Vectors 2020 Oct 16;13(1):521. Epub 2020 Oct 16.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia.

Background: Blastocystis is a protist that lives in the intestinal tract of a variety of hosts, including humans. It is still unclear how Blastocystis causes disease, which presents an ongoing challenge for researchers. Despite the controversial findings on the association between Blastocystis and clinical digestive manifestations, there is currently no consensus as to whether this protozoan actually behaves as a pathogen in humans. Furthermore, the relationship between Blastocystis and the intestinal microbiota composition is not yet clear. For that reason, the aim of this study was to identify if colonization by Blastocystis is related to changes in the diversity and relative abundance of bacterial communities, compared with those of Blastocystis-free individuals in a group of Colombian children.

Methods: We took stool samples from 57 school-aged children attending a daycare institution in Popayán (Southwest Colombia). Whole DNA was extracted and examined by 16S-rRNA amplicon-based sequencing. Blastocystis was detected by real time PCR and other intestinal parasites were detected by microscopy. We evaluated if Blastocystis was associated with host variables and the diversity and abundance of microbial communities.

Results: The composition of the intestinal bacterial community was not significantly different between Blastocystis-free and Blastocystis-colonized children. Despite this, we observed a higher microbial richness in the intestines of children colonized by Blastocystis, which could, therefore, be considered a benefit to intestinal health. The phylum Firmicutes was the predominant taxonomic unit in both groups analyzed. In Blastocystis-free individuals, there was a higher proportion of Bacteroidetes; similarly, in children colonized by Blastocystis, there was a higher relative abundance of the phylum Proteobacteria; however, no statistically significant differences were found between the comparison groups.

Conclusions: The presence of Blastocystis showed a decrease in Bacteroides, and an increase in the relative abundance of the genus Faecalibacterium. It was also evident that the presence of Blastocystis was unrelated to dysbiosis at the intestinal level; on the contrary, its presence did not show statistically differences in the intestinal microbiota composition. Nevertheless, we believe that Blastocystis plays a role in the ecology of the intestinal microbiota through its interaction with other microbial components.
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http://dx.doi.org/10.1186/s13071-020-04392-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565366PMC
October 2020

Identification of blood-feeding sources in Panstrongylus, Psammolestes, Rhodnius and Triatoma using amplicon-based next-generation sequencing.

Parasit Vectors 2020 Aug 31;13(1):434. Epub 2020 Aug 31.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia.

Background: Triatomines are hematophagous insects that play an important role as vectors of Trypanosoma cruzi, the causative agent of Chagas disease. These insects have adapted to multiple blood-feeding sources that can affect relevant aspects of their life-cycle and interactions, thereby influencing parasitic transmission dynamics. We conducted a characterization of the feeding sources of individuals from the primary circulating triatomine genera in Colombia using amplicon-based next-generation sequencing (NGS).

Methods: We used 42 triatomines collected in different departments of Colombia. DNA was extracted from the gut. The presence of T. cruzi was identified using real-time PCR, and discrete typing units (DTUs) were determined by conventional PCR. For blood-feeding source identification, PCR products of the vertebrate 12S rRNA gene were obtained and sequenced by next-generation sequencing (NGS). Blood-meal sources were inferred using blastn against a curated reference dataset containing the 12S rRNA sequences belonging to vertebrates with a distribution in South America that represent a potential feeding source for triatomine bugs. Mean and median comparison tests were performed to evaluate differences in triatomine blood-feeding sources, infection state, and geographical regions. Lastly, the inverse Simpson's diversity index was calculated.

Results: The overall frequency of T. cruzi infection was 83.3%. TcI was found as the most predominant DTU (65.7%). A total of 67 feeding sources were detected from the analyses of approximately 7 million reads. The predominant feeding source found was Homo sapiens (76.8%), followed by birds (10.5%), artiodactyls (4.4%), and non-human primates (3.9%). There were differences among numerous feeding sources of triatomines of different species. The diversity of feeding sources also differed depending on the presence of T. cruzi.

Conclusions: To the best of our knowledge, this is the first study to employ amplicon-based NGS of the 12S rRNA gene to depict blood-feeding sources of multiple triatomine species collected in different regions of Colombia. Our findings report a striking read diversity that has not been reported previously. This is a powerful approach to unravel transmission dynamics at microgeographical levels.
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http://dx.doi.org/10.1186/s13071-020-04310-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457505PMC
August 2020

The arrival and spread of SARS-CoV-2 in Colombia.

J Med Virol 2021 02 13;93(2):1158-1163. Epub 2020 Aug 13.

Icahn School of Medicine at Mount Sinai, New York, New York.

We performed phylogenomic analysis of severe acute respiratory syndrome coronavirus-2 from 88 infected individuals across different regions of Colombia. Eleven different lineages were detected, suggesting multiple introduction events. Pangolin lineages B.1 and B.1.5 were the most frequent, with B.1 being associated with prior travel to high-risk areas.
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http://dx.doi.org/10.1002/jmv.26393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436700PMC
February 2021

Genetic Diversity Among SARS-CoV2 Strains in South America may Impact Performance of Molecular Detection.

Pathogens 2020 Jul 17;9(7). Epub 2020 Jul 17.

Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Since its emergence in Wuhan (China) on December 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide. After its arrival in South America in February 2020, the virus has expanded throughout the region, infecting over 900,000 individuals with approximately 41,000 reported deaths to date. In response to the rapidly growing number of cases, a number of different primer-probe sets have been developed. However, despite being highly specific, most of these primer-probe sets are known to exhibit variable sensitivity. Currently, there are more than 300 SARS-CoV2 whole genome sequences deposited in databases from Brazil, Chile, Ecuador, Colombia, Uruguay, Peru, and Argentina. To test how regional viral diversity may impact oligo binding sites and affect test performance, we reviewed all available primer-probe sets targeting the E, N, and RdRp genes against available South American SARS-CoV-2 genomes checking for nucleotide variations in annealing sites. Results from this in silico analysis showed no nucleotide variations on the E-gene target region, in contrast to the N and RdRp genes which showed massive nucleotide variations within oligo binding sites. In lines with previous data, our results suggest that the E-gene stands as the most conserved and reliable target when considering single-gene target testing for molecular diagnosis of SARS-CoV-2 in South America.
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http://dx.doi.org/10.3390/pathogens9070580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400710PMC
July 2020

Development of a Multilocus Sequence Typing Scheme for .

Genes (Basel) 2020 07 8;11(7). Epub 2020 Jul 8.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá 111211, Colombia.

is an intestinal protozoan most commonly found in humans. It has been grouped into 8 assemblages (A-H). Markers such as the glutamate dehydrogenase gene, triose phosphate isomerase and beta-giardin (β-giardin) have been widely used for genotyping. In addition, different genetic targets have been proposed as a valuable alternative to assess diversity and genetics of this microorganism. Thus, our objective was to evaluate new markers for the study of the diversity and intra-taxa genetic structure of in silico and in DNA obtained from stool samples. We analysed nine constitutive genes in 80 complete genome sequences and in a group of 24 stool samples from Colombia. Allelic diversity was evaluated by locus and for the concatenated sequence of nine loci that could discriminate up to 53 alleles. Phylogenetic reconstructions allowed us to identify AI, AII and B assemblages. We found evidence of intra- and inter-assemblage recombination events. Population structure analysis showed genetic differentiation among the assemblages analysed.
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http://dx.doi.org/10.3390/genes11070764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397270PMC
July 2020

Slight temperature changes cause rapid transcriptomic responses in Trypanosoma cruzi metacyclic trypomastigotes.

Parasit Vectors 2020 May 14;13(1):255. Epub 2020 May 14.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia.

Background: Severe changes in temperature can affect the behavior and ecology of some infectious agents. Trypanosoma cruzi is a protozoan that causes Chagas disease. This parasite has high genetic variability and can be divided into six discrete typing units (DTUs). Trypanosoma cruzi also has a complex life-cycle, which includes the process of metacyclogenesis when non-infective epimastigote forms are differentiated into infective metacyclic trypomastigotes (MT). Studies in triatomines have shown that changes in temperature also affect the number and viability of MT.

Methods: The objective of this study was to evaluate how temperature affects the transcriptional profiles of T. cruzi I and II (TcI and TcII) MT by exposing parasites to two temperatures (27 °C and 28 °C) and comparing those to normal culture conditions at 26 °C. Subsequently, RNA-seq was conducted and differentially expressed genes were quantified and associated to metabolic pathways.

Results: A statistically significant difference was observed in the number of MT between the temperatures evaluated and the control, TcII DTU was not strongly affected to exposure to high temperatures compared to TcI. Similar results were found when we analyzed gene expression in this DTU, with the greatest number of differentially expressed genes being observed at 28 °C, which could indicate a dysregulation of different signaling pathways under this temperature. Chromosome analysis indicated that chromosome 1 harbored the highest number of changes for both DTUs for all thermal treatments. Finally, gene ontology (GO) analyses showed a decrease in the coding RNAs involved in the regulation of processes related to the metabolism of lipids and carbohydrates, the evasion of oxidative stress, and proteolysis and phosphorylation processes, and a decrease in RNAs coding to ribosomal proteins in TcI and TcII, along with an increase in the expression of surface metalloprotease GP63 in TcII.

Conclusions: Slight temperature shifts lead to increased cell death of metacyclic trypomastigotes because of the deregulation of gene expression of different processes essential for the TcI and TcII DTUs of T. cruzi.
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http://dx.doi.org/10.1186/s13071-020-04125-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226949PMC
May 2020

Occurrence of in Patients with Infection.

Pathogens 2020 Apr 14;9(4). Epub 2020 Apr 14.

Grupo de Investigaciones Microbiológicas de la Universidad del Rosario (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá 110221, Colombia.

comprises a public-health threat that has been understudied in Colombia. Hypervirulent strains of harbor multiple toxins, can be easily spread, and can have their onset of disease within healthcare facilities (HCFO) and the community (CO). Studies have shown that a disrupted microbiota (e.g., dysbiosis) may allow infection (CDI). It has been suggested that dysbiosis prevents colonization by the anaerobic eukaryote , possibly due to an increase in luminal oxygen tension. No study has found co-occurrence of CDI and . Therefore, we aimed to determine the frequencies of and infection/colonization in 220 diarrheal fecal samples. Molecular detection by PCR for both microorganisms was performed, with descriptive analyses of four variables (CDI detection, determination of toxigenic profiles, detection, and patient site of onset). We demonstrate a significant association between the presence of and CDI, with coinfection found in 61 patients, and show a high frequency of CDI among both HCFO and CO groups. Our results of coinfection frequencies could support hypotheses that suggest can adapt to dysbiosis and oxidative stress. Further, the presence of toxigenic occurring outside healthcare facilities shown here raises the alarm for community wide spread.
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http://dx.doi.org/10.3390/pathogens9040283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238161PMC
April 2020

Human Papillomavirus (HPV69/HPV73) Coinfection associated with Simultaneous Squamous Cell Carcinoma of the Anus and Presumed Lung Metastasis.

Viruses 2020 03 22;12(3). Epub 2020 Mar 22.

Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Background: Human papillomaviruses (HPVs) have been linked to a variety of human cancers. As the landscape of HPV-related neoplasia continues to expand, uncommon and rare HPV genotypes have also started to emerge. Host-virus interplay is recognized as a key driver in HPV carcinogenesis, with host immune status, virus genetic variants and coinfection highly influencing the dynamics of malignant transformation. Immunosuppression and tissue tropism are also known to influence HPV pathogenesis.

Methods: Herein, we present a case of a patient who, in the setting of HIV positivity, developed anal squamous cell carcinoma associated with HPV69 and later developed squamous cell carcinoma in the lungs, clinically presumed to be metastatic disease, associated with HPV73. Consensus PCR screening for HPV was performed by real-time PCR amplification of the L1 gene region, amplification of the E6 regions with High-Resolution Melting Curve Analysis followed by Sanger sequencing confirmation and phylogenetic analysis.

Results: Sanger sequencing of the consensus PCR amplification product determined that the anal tissue sample was positive for HPV 69, and the lung tissue sample was positive for HPV 73.

Conclusions: This case underscores the importance of recognizing the emerging role of these rare "possibly carcinogenic" HPV types in human carcinogenesis.
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http://dx.doi.org/10.3390/v12030349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150817PMC
March 2020

Intraspecific Genomic Divergence and Minor Structural Variations in .

Genes (Basel) 2020 02 27;11(3). Epub 2020 Feb 27.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá 110211, Colombia.

is one of the most important species associated with cutaneous leishmaniasis (CL) in Latin America. Despite its wide geographic distribution and pathogenic potential in humans and animals, the genomic variability of this species is low compared with other species circulating in the same geographical area. No studies have reported a detailed analysis of the whole genome of from clinical isolates using DNA high-throughput sequencing to clarify its intraspecific genomic variability or plausible divergence. Therefore, this study aimed to evaluate the intraspecific genomic variability of from Colombia and Panama. A total of 22 genomes were analyzed, 19 from Colombian patients with CL and three genomes from Panama obtained from public databases. The phylogenomic analysis revealed the potential existence of three well-supported clades as evidence of intraspecific divergence. Additionally, the whole-genome analysis showed low structural variations in terms of ploidy, copy number variations, and single-nucleotide polymorphisms (SNPs). SNPs shared among all clades were identified, revealing their importance in different biological processes of . The findings not only expand our knowledge of intraspecific genomic variability of one of the most important species in South America but also highlights the possible existence of different clades/lineages/subpopulations across a geographic scale.
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http://dx.doi.org/10.3390/genes11030252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140786PMC
February 2020

Genomic analyses reveal moderate levels of ploidy, high heterozygosity and structural variations in a Colombian isolate of Leishmania (Leishmania) amazonensis.

Acta Trop 2020 Mar 10;203:105296. Epub 2019 Dec 10.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales y Matemáticas, Universidad del Rosario, Bogotá, Colombia.. Electronic address:

Leishmania amazonensis is one of the causative agents of the different forms of cutaneous leishmaniasis present in Latin America. This species has been isolated from humans and animals (canine/feline) in some endemic regions of Colombia. Therefore, L. amazonensis is of great relevance at the clinical and epidemiological levels in medicine and veterinary science. Until now, very few genomes from this species are available. Here, we report the complete genome sequence of a laboratory-adapted L. amazonensis strain isolated from a human patient with clinical manifestation of cutaneous leishmaniasis in Colombia. The genome sequence not only allowed inter and intra-species comparative analyses to be performed with the sequenced genomes of L. amazonensis strains from different geographical regions, but also increased our knowledge about the genomic behavior of this L. amazonensis Colombian strain. This isolate was also characterized in terms of single nucleotide polymorphisms, chromosome and gene copy number variations (CNVs). The results revealed moderate aneuploidy, CNVs in genes involved in the virulence, growth, and survival of the parasite, and in the distributions of the multicopy genes on some chromosomes, as well as a high level of heterozygosity. The data confirmed previous reports that identified unique variations in L. amazonensis, suggesting aneuploidy may not have a high fitness cost and may allow the rapid generation of diversity in Leishmania parasites growing normally.
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http://dx.doi.org/10.1016/j.actatropica.2019.105296DOI Listing
March 2020

Long-term outcome in a case series of Denys-Drash syndrome.

Clin Kidney J 2019 Dec 16;12(6):836-839. Epub 2019 Mar 16.

Pediatric Nephrology, Hospital Universitario Vall d'Hebron, Passeig de la Vall d'Hebron, Barcelona, Spain.

Background: Denys-Drash syndrome (DDS) is a rare disease caused by mutations in exons 8 and 9 of the gene. It is characterized by the association of early onset steroid-resistant nephrotic syndrome (SRNS), Wilms' tumour and, in some patients, intersex disorders, with increasing risk of gonadoblastoma. There are few published data concerning the long-term outcome of patients with DDS. The aim of this study was to report our experience.

Methods: Data were collected from five children (three boys) with confirmed DDS diagnosed from 1996 to 2017. The mean follow-up of these patients was 16 years.

Results: The patients presented with SRNS and diffuse mesangial sclerosis at renal biopsy. All patients were hypertensive and progressed to end-stage kidney disease, initiating dialysis at a mean age of 28 months. Three patients developed Wilms' tumour 9 months after the SRNS was identified, which was treated by nephrectomy and chemotherapy. All five patients received kidney transplantation. SRNS did not recur after transplantation in any of the patients and graft survival was similar to that of other kidney transplant recipients in our programme. All three boys had ambiguous genitalia and cryptorchidism but a confirmed male karyotype (46, XY). One girl presented with gonadal agenesis, whereas the other one had normal female ovarian tissue and external genitalia. Both girls had a female karyotype (46, XX). Gonadoblastoma was not observed at any case.

Conclusions: Early DDS recognition in patients with SRNS is crucial due to its low prevalence, the specific treatment approach required and early detection of Wilms' tumour. Few data are available regarding long-term outcomes.
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http://dx.doi.org/10.1093/ckj/sfz022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885669PMC
December 2019

Mice lacking angiotensin type 2 receptor exhibit a sex-specific attenuation of insulin sensitivity.

Mol Cell Endocrinol 2019 12 17;498:110587. Epub 2019 Sep 17.

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Biológica, IQUIFIB (UBA-CONICET), Buenos Aires, Argentina. Electronic address:

The renin-angiotensin system modulates insulin action. Pharmacological stimulation of angiotensin type 2 receptor (AT2R) was shown to have beneficial metabolic effects in various animal models of insulin resistance and type 2 diabetes and also to increase insulin sensitivity in wild type mice. In this study we further explored the role of the AT2R on insulin action and glucose homeostasis by investigating the glycemic profile and in vivo insulin signaling status in insulin-target tissues from both male and female AT2R knockout (KO) mice. When compared to the respective wild-type (WT) group, glycemia and insulinemia was unaltered in AT2RKO mice regardless of sex. However, female AT2RKO mice displayed decreased insulin sensitivity compared to their WT littermates. This was accompanied by a compensatory increase in adiponectinemia and with a specific attenuation of the activity of main insulin signaling components (insulin receptor, Akt and ERK1/2) in adipose tissue with no apparent alterations in insulin signaling in either liver or skeletal muscle. These parameters remained unaltered in male AT2RKO mice as compared to male WT mice. Present data show that the AT2R has a physiological role in the conservation of insulin action in female but not in male mice. Our results suggest a sexual dimorphism in the control of insulin action and glucose homeostasis by the AT2R and reinforce the notion that pharmacological modulation of the balance between the AT1R and AT2R receptor could be important for treatment of metabolic syndrome and type 2 diabetes.
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http://dx.doi.org/10.1016/j.mce.2019.110587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903409PMC
December 2019

Integrated genomic epidemiology and phenotypic profiling of Clostridium difficile across intra-hospital and community populations in Colombia.

Sci Rep 2019 08 5;9(1):11293. Epub 2019 Aug 5.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales y Matemáticas, Universidad del Rosario, Bogotá, Colombia.

Clostridium difficile, the causal agent of antibiotic-associated diarrhea, has a complex epidemiology poorly studied in Latin America. We performed a robust genomic and phenotypic profiling of 53 C. difficile clinical isolates established from diarrheal samples from either intrahospital (IH) or community (CO) populations in central Colombia. In vitro tests were conducted to evaluate the cytopathic effect, the minimum inhibitory concentration of ten antimicrobial agents, the sporulation efficiency and the colony forming ability. Eleven different sequence types (STs) were found, the majority present individually in each sample, however in three samples two different STs were isolated. Interestingly, CO patients were infected with STs associated with hypervirulent strains (ST-1 in Clade-2). Three coexistence events (two STs simultaneously detected in the same sample) were observed always involving ST-8 from Clade-1. A total of 2,502 genes were present in 99% of the isolates with 95% of identity or more, it represents a core genome of 28.6% of the 8,735 total genes identified in the set of genomes. A high cytopathic effect was observed for the isolates positive for the two main toxins but negative for binary toxin (TcdA+/TcdB+/CDT- toxin production type), found only in Clade-1. Molecular markers conferring resistance to fluoroquinolones (cdeA and gyrA) and to sulfonamides (folP) were the most frequent in the analyzed genomes. In addition, 15 other markers were found mostly in Clade-2 isolates. These results highlight the regional differences that C. difficile isolates display, being in this case the CO isolates the ones having a greater number of accessory genes and virulence-associated factors.
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http://dx.doi.org/10.1038/s41598-019-47688-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683185PMC
August 2019

Comparative genomics identifies potential virulence factors in and .

Virulence 2019 12;10(1):657-676

a Grupo de Investigaciones Microbiológicas - UR (GIMUR), Programa de Biología, Facultad de Ciencias Naturales y Matemáticas , Universidad del Rosario , Bogotá , Colombia.

Some well-known Clostridiales species such as and are agents of high impact diseases worldwide. Nevertheless, other foreseen Clostridiales species have recently emerged such as and . Three fecal isolates were identified as (Gcol.A2 and Gcol.A43) and (Gcol.A11) during public health screening for infections in Colombia. genomes were highly diverse and contained large numbers of accessory genes. Genetic diversity and accessory gene percentage were lower among the genomes than in the genomes. and toxins encoding homologous sequences and other potential virulence factors were also identified. interferase, a toxic component of the type II toxin-antitoxin system, was found among the genomes. was the only toxin encoding gene detected in Gcol.A43, the Colombian isolate with an experimentally-determined high cytotoxic effect. Gcol.A2 and Gcol.A43 had higher sporulation efficiencies than Gcol.A11 (84.5%, 83.8% and 57.0%, respectively), as supported by the greater number of proteins associated with sporulation pathways in the genomes compared with the genomes (33.3 and 28.4 on average, respectively). This work allowed complete genome description of two clostridiales species revealing high levels of intra-taxa diversity, accessory genomes containing virulence-factors encoding genes (especially in ), with proteins involved in sporulation processes more highly represented in . These finding suggest the need to advance in the study of those species with potential importance at public health level.
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http://dx.doi.org/10.1080/21505594.2019.1637699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629180PMC
December 2019