13 results on '"Graña-Miraglia, Lucía"'
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2. Total substitution and partial modification of the set of non-ribosomal peptide synthetases clusters lead to pyoverdine diversity in the Pseudomonas fluorescens complex.
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Graña-Miraglia L, Geney Higuita JL, Salazar JC, Guaya Iñiguez D, Alcolado León C, and García-Angulo VA
- Abstract
Pyoverdines are high affinity siderophores produced by most Pseudomonas with a wide role in microbial interspecies interactions. They are primarily composed of a conserved chromophore moiety, an acyl side chain and a peptide backbone which may be highly variable among strains. Upon ferric iron sequestration, pyoverdines are internalized through specialized receptors. The peptide precursor of pyoverdine, termed ferribactin, is synthesized by a set of non-ribosomal peptide synthetase (NRPS) enzymes and further modified by tailoring enzymes. While PvdL, the NRPS responsible for the synthesis of the peptide moiety that derives into the chromophore is conserved, the NRPSs for the peptide backbone are different across fluorescent Pseudomonas . Although the variation of pyoverdine is a widely recognized characteristic within the genus, the evolutionary events associated with the diversity and distribution of this trait remain mostly unknown. This study analyzed the NRPSs clusters for the biosynthesis of the peptide backbone of ferribactin in the genomes of a representative subset of strains of the Pseudomonas fluorescens complex. Bioinformatic analysis of the specificity of adenylation domains of the NRPSs allowed the prediction of 30 different pyoverdine variants. Phylogenetic reconstruction and mapping of the NRPS clusters pinpointed two different general levels of modifications. In the first level, a complete replacement of the set of NRPRs by horizontal transfer occurs. In the second level, the original set of NRPSs is modified through different mechanisms, including partial substitution of the NRPS genes by horizontal transfer, adenylation domain specificity change or NRPS accessory domain gain/loss., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Graña-Miraglia, Geney Higuita, Salazar, Guaya Iñiguez, Alcolado León and García-Angulo.)
- Published
- 2024
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3. Predictive modeling of antibiotic eradication therapy success for new-onset Pseudomonas aeruginosa pulmonary infections in children with cystic fibrosis.
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Graña-Miraglia L, Morales-Lizcano N, Wang PW, Hwang DM, Yau YCW, Waters VJ, and Guttman DS
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- Humans, Child, Pseudomonas aeruginosa, Cell Aggregation, Lung, Anti-Bacterial Agents therapeutic use, Cystic Fibrosis complications, Cystic Fibrosis drug therapy, Pseudomonas Infections complications, Pseudomonas Infections drug therapy
- Abstract
Chronic Pseudomonas aeruginosa (Pa) lung infections are the leading cause of mortality among cystic fibrosis (CF) patients; therefore, the eradication of new-onset Pa lung infections is an important therapeutic goal that can have long-term health benefits. The use of early antibiotic eradication therapy (AET) has been shown to clear the majority of new-onset Pa infections, and it is hoped that identifying the underlying basis for AET failure will further improve treatment outcomes. Here we generated machine learning models to predict AET outcomes based on pathogen genomic data. We used a nested cross validation design, population structure control, and recursive feature selection to improve model performance and showed that incorporating population structure control was crucial for improving model interpretation and generalizability. Our best model, controlling for population structure and using only 30 recursively selected features, had an area under the curve of 0.87 for a holdout test dataset. The top-ranked features were generally associated with motility, adhesion, and biofilm formation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Graña-Miraglia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
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4. Evolutionary History and Strength of Selection Determine the Rate of Antibiotic Resistance Adaptation.
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Cisneros-Mayoral S, Graña-Miraglia L, Pérez-Morales D, Peña-Miller R, and Fuentes-Hernández A
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- Adaptation, Physiological genetics, Anti-Bacterial Agents pharmacology, Mutation, Drug Resistance, Bacterial genetics, Escherichia coli genetics
- Abstract
Bacterial adaptation to stressful environments often produces evolutionary constraints whereby increases in resistance are associated with reduced fitness in a different environment. The exploitation of this resistance-cost trade-off has been proposed as the basis of rational antimicrobial treatment strategies designed to limit the evolution of drug resistance in bacterial pathogens. Recent theoretical, laboratory, and clinical studies have shown that fluctuating selection can maintain drug efficacy and even restore drug susceptibility, but can also increase the rate of adaptation and promote cross-resistance to other antibiotics. In this paper, we combine mathematical modeling, experimental evolution, and whole-genome sequencing to follow evolutionary trajectories towards β-lactam resistance under fluctuating selective conditions. Our experimental model system consists of eight populations of Escherichia coli K12 evolving in parallel to a serial dilution protocol designed to dynamically control the strength of selection for resistance. We implemented adaptive ramps with mild and strong selection, resulting in evolved populations with similar levels of resistance, but with different evolutionary dynamics and diverging genotypic profiles. We found that mutations that emerged under strong selection are unstable in the absence of selection, in contrast to resistance mutations previously selected in the mild selection regime that were stably maintained in drug-free environments and positively selected for when antibiotics were reintroduced. Altogether, our population dynamics model and the phenotypic and genomic analysis of the evolved populations show that the rate of resistance adaptation is contingent upon the strength of selection, but also on evolutionary constraints imposed by prior drug exposures., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)
- Published
- 2022
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5. Spirochetes isolated from arthropods constitute a novel genus Entomospira genus novum within the order Spirochaetales.
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Graña-Miraglia L, Sikutova S, Vancová M, Bílý T, Fingerle V, Sing A, Castillo-Ramírez S, Margos G, and Rudolf I
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- Animals, Arthropods genetics, Bacterial Typing Techniques methods, Base Composition genetics, DNA, Bacterial genetics, Phylogeny, RNA, Ribosomal, 16S genetics, Sequence Analysis, DNA methods, Spirochaeta genetics, Spirochaetales classification, Spirochaetales genetics, Spirochaetales isolation & purification
- Abstract
Spirochetal bacteria were successfully isolated from mosquitoes (Culex pipiens, Aedes cinereus) in the Czech Republic between 1999 and 2002. Preliminary 16S rRNA phylogenetic sequence analysis showed that these strains differed significantly from other spirochetal genera within the family Spirochaetaceae and suggested a novel bacterial genus in this family. To obtain more comprehensive genomic information of these isolates, we used Illumina MiSeq and Oxford Nanopore technologies to sequence four genomes of these spirochetes (BR151, BR149, BR193, BR208). The overall size of the genomes varied between 1.68 and 1.78 Mb; the GC content ranged from 38.5 to 45.8%. Draft genomes were compared to 36 publicly available genomes encompassing eight genera from the class Spirochaetes. A phylogeny generated from orthologous genes across all taxa and the percentage of conserved proteins (POCP) confirmed the genus status of these novel spirochetes. The genus Entomospira gen. nov. is proposed with BR151 selected as type species of the genus. For this isolate and the closest related isolate, BR149, we propose the species name Entomospira culicis sp. nov. The two other isolates BR208 and BR193 are named Entomospira nematocera sp. nov. (BR208) and Entomospira entomophilus sp. nov. (BR193). Finally, we discuss their interesting phylogenetic positioning.
- Published
- 2020
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6. Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide.
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Isabel S, Graña-Miraglia L, Gutierrez JM, Bundalovic-Torma C, Groves HE, Isabel MR, Eshaghi A, Patel SN, Gubbay JB, Poutanen T, Guttman DS, and Poutanen SM
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- Adolescent, Adult, Aged, Aged, 80 and over, Angiotensin-Converting Enzyme 2, Base Sequence, Betacoronavirus pathogenicity, COVID-19, Child, Child, Preschool, Computer Simulation, Coronavirus Infections virology, Female, Genome, Viral genetics, Humans, Infant, Male, Middle Aged, Mutation, Missense, Pandemics, Peptidyl-Dipeptidase A metabolism, Phylogeny, Pneumonia, Viral virology, Protein Conformation, SARS-CoV-2, Spike Glycoprotein, Coronavirus metabolism, Virulence genetics, Young Adult, Betacoronavirus chemistry, Coronavirus Infections epidemiology, Evolution, Molecular, Pneumonia, Viral epidemiology, Spike Glycoprotein, Coronavirus chemistry, Spike Glycoprotein, Coronavirus genetics
- Abstract
The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared on March 11, 2020 by the World Health Organization. As of the 31st of May, 2020, there have been more than 6 million COVID-19 cases diagnosed worldwide and over 370,000 deaths, according to Johns Hopkins. Thousands of SARS-CoV-2 strains have been sequenced to date, providing a valuable opportunity to investigate the evolution of the virus on a global scale. We performed a phylogenetic analysis of over 1,225 SARS-CoV-2 genomes spanning from late December 2019 to mid-March 2020. We identified a missense mutation, D614G, in the spike protein of SARS-CoV-2, which has emerged as a predominant clade in Europe (954 of 1,449 (66%) sequences) and is spreading worldwide (1,237 of 2,795 (44%) sequences). Molecular dating analysis estimated the emergence of this clade around mid-to-late January (10-25 January) 2020. We also applied structural bioinformatics to assess the potential impact of D614G on the virulence and epidemiology of SARS-CoV-2. In silico analyses on the spike protein structure suggests that the mutation is most likely neutral to protein function as it relates to its interaction with the human ACE2 receptor. The lack of clinical metadata available prevented our investigation of association between viral clade and disease severity phenotype. Future work that can leverage clinical outcome data with both viral and human genomic diversity is needed to monitor the pandemic.
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- 2020
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7. Rejection of the name Borreliella and all proposed species comb. nov. placed therein.
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Margos G, Castillo-Ramirez S, Cutler S, Dessau RB, Eikeland R, Estrada-Peña A, Gofton A, Graña-Miraglia L, Hunfeld KP, Krause A, Lienhard R, Lindgren PE, Oskam C, Rudolf I, Schwartz I, Sing A, Stevenson B, Wormser GP, and Fingerle V
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- Phylogeny, Spirochaetales classification, Terminology as Topic
- Abstract
Rejection ( nomen rejiciendum ) of the name Borreliella and all new combinations therein is being requested on grounds of risk to human health and patient safety (Principle 1, subprinciple 2 and Rule 56a) and violation to aim for stability of names, to avoid useless creation of names (Principle 1, subprinciple 1 and 3) and that names should not be changed without sufficient reason (Principle 9 of the International Code of Nomenclature of Prokaryotes).
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- 2020
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8. Phylogenomics Reveals Clear Cases of Misclassification and Genus-Wide Phylogenetic Markers for Acinetobacter.
- Author
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Mateo-Estrada V, Graña-Miraglia L, López-Leal G, and Castillo-Ramírez S
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- Biological Evolution, Genetic Markers, Genetic Speciation, Phylogeny, Acinetobacter classification, Acinetobacter genetics
- Abstract
The Gram-negative Acinetobacter genus has several species of clear medical relevance. Many fully sequenced genomes belonging to the genus have been published in recent years; however, there has not been a recent attempt to infer the evolutionary history of Acinetobacter with that vast amount of information. Here, through a phylogenomic approach, we established the most up-to-date view of the evolutionary relationships within this genus and highlighted several cases of poor classification, especially for the very closely related species within the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (Acb complex). Furthermore, we determined appropriate phylogenetic markers for this genus and showed that concatenation of the top 13 gives a very decent reflection of the evolutionary relationships for the genus Acinetobacter. The intersection between our top markers and previously defined universal markers is very small. In general, our study shows that, although there seems to be hardly any universal markers, bespoke phylogenomic approaches can be used to infer the phylogeny of different bacterial genera. We expect that ad hoc phylogenomic approaches will be the standard in the years to come and will provide enough information to resolve intricate evolutionary relationships like those observed in the Acb complex., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)
- Published
- 2019
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9. Unexplored Genetic Diversity of Multidrug- and Extremely Drug-Resistant Acinetobacter baumannii Isolates from Tertiary Hospitals in Honduras.
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López-Leal G, Zuniga-Moya JC, Castro-Jaimes S, Graña-Miraglia L, Pérez-Oseguera Á, Reyes-García HS, Gough-Coto SD, Pavón-Madrid R, Bejarano SA, Ferrera A, Castillo-Ramírez S, and Cevallos MA
- Subjects
- Acinetobacter Infections drug therapy, Acinetobacter Infections microbiology, Acinetobacter baumannii classification, Acinetobacter baumannii drug effects, Acinetobacter baumannii isolation & purification, Anti-Bacterial Agents pharmacology, Clone Cells, Epidemiological Monitoring, Gene Expression, Genetic Variation, Honduras epidemiology, Humans, Microbial Sensitivity Tests, Multilocus Sequence Typing, Phylogeny, Plasmids chemistry, Plasmids metabolism, Tertiary Care Centers, Whole Genome Sequencing, beta-Lactamases metabolism, Acinetobacter Infections epidemiology, Acinetobacter baumannii genetics, Drug Resistance, Multiple, Bacterial genetics, Genes, Bacterial, Genome, Bacterial, beta-Lactamases genetics
- Abstract
Although Acinetobacter baumannii has become one of the most important nosocomial pathogens worldwide, very little is known about the genetic identity of isolates from less developed countries in Latin America. To alleviate this, we sequenced the genomes of 16 A. baumannii isolates from Honduras. Whole-genome sequencing was conducted on 16 isolates from five Honduran Hospitals. With the sequences of these Honduran isolates and other 42 publically available genomes, a maximum likelihood phylogeny was constructed to establish the relationship between the Honduran isolates and those belonging to the International Clones (ICs). In addition, sequence type (ST) assignation was conducted by the PubMLST, and antibiotic resistance genes were identified using ResFinder. The Honduran isolates are highly diverse and contain new allele combinations under the Bartual multilocus sequence typing scheme. The most common STs were ST
B 447/STP 10 and STB 758/STP 156. Furthermore, none of these isolates belongs to clonal complexes related to the ICs. Antibiotic susceptibility profiles of these isolates showed that they are multidrug resistant (MDR) or extensively drug resistant (XDR). In addition, the Honduran isolates had genes involved in resistance to seven antibiotic families. For instance, several bla OXA alleles were found, including bla OXA-23 and a gene encoding the metallo-beta-lactamase NDM-1. Notably, nine of the Honduran isolates have antibiotic resistance genes to three or more antibiotic families. In summary, in this study, we unveiled an untapped source of genetic diversity of MDR and XDR isolates; notably, these isolates did not belong to the well-known ICs.- Published
- 2019
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10. Inaccurate Multilocus Sequence Typing of Acinetobacter baumannii.
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Castillo-Ramírez S and Graña-Miraglia L
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- Acinetobacter baumannii genetics, Acinetobacter baumannii isolation & purification, Bacterial Typing Techniques, Genotyping Techniques, Humans, Multilocus Sequence Typing, Phylogeny, Acinetobacter Infections microbiology, Acinetobacter baumannii classification, Genome, Bacterial genetics
- Abstract
Multilocus sequence typing has been useful for genotyping pathogens in surveillance and epidemiologic studies. However, it cannot reflect the true relationships of isolates for species with very dynamic genomes. Using a robust genome phylogeny, we demonstrated the limitations of this method for typing Acinetobacter baumannii.
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- 2019
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11. Rapid Gene Turnover as a Significant Source of Genetic Variation in a Recently Seeded Population of a Healthcare-Associated Pathogen.
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Graña-Miraglia L, Lozano LF, Velázquez C, Volkow-Fernández P, Pérez-Oseguera Á, Cevallos MA, and Castillo-Ramírez S
- Abstract
Genome sequencing has been useful to gain an understanding of bacterial evolution. It has been used for studying the phylogeography and/or the impact of mutation and recombination on bacterial populations. However, it has rarely been used to study gene turnover at microevolutionary scales. Here, we sequenced Mexican strains of the human pathogen Acinetobacter baumannii sampled from the same locale over a 3 year period to obtain insights into the microevolutionary dynamics of gene content variability. We found that the Mexican A. baumannii population was recently founded and has been emerging due to a rapid clonal expansion. Furthermore, we noticed that on average the Mexican strains differed from each other by over 300 genes and, notably, this gene content variation has accrued more frequently and faster than the accumulation of mutations. Moreover, due to its rapid pace, gene content variation reflects the phylogeny only at very short periods of time. Additionally, we found that the external branches of the phylogeny had almost 100 more genes than the internal branches. All in all, these results show that rapid gene turnover has been of paramount importance in producing genetic variation within this population and demonstrate the utility of genome sequencing to study alternative forms of genetic variation.
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- 2017
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12. Complete Genome Sequence of a Multidrug-Resistant Acinetobacter baumannii Isolate Obtained from a Mexican Hospital (Sequence Type 422).
- Author
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Castro-Jaimes S, Salgado-Camargo AD, Graña-Miraglia L, Lozano L, Bocanegra-Ibarias P, Volkow-Fernández P, Silva-Sanchez J, Castillo-Ramírez S, and Cevallos MA
- Abstract
Acinetobacter baumannii has emerged as a dangerous nosocomial pathogen, particularly for severely ill patients in intensive care units and patients with hematologic malignancies. Here, we present the complete genome sequence of a multidrug-resistant A. baumannii isolate, recovered from a Mexican hospital and classified as sequence type 422 according to the multilocus sequence typing Pasteur scheme., (Copyright © 2016 Castro-Jaimes et al.)
- Published
- 2016
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13. First Genome Sequence of a Mexican Multidrug-Resistant Acinetobacter baumannii Isolate.
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Graña-Miraglia L, Lozano L, Castro-Jaimes S, Cevallos MA, Volkow P, and Castillo-Ramírez S
- Abstract
Acinetobacter baumanniihas emerged as an important nosocomial pathogen worldwide. Here, we present the draft genome of the first multidrug-resistantA. baumanniiisolate, sampled from a tertiary hospital in Mexico City. This genome will provide a starting point for studying the genomic diversity of this species in Mexico., (Copyright © 2016 Graña-Miraglia et al.)
- Published
- 2016
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