Biology subjects

Tarifeno-Saldivia, E.

Publications and source records attributed to Tarifeno-Saldivia, E..

3 recordsLinked to original sources

bioRxiv2024

Biofilm formation on glycated collagen modulates Streptococcus mutans bacterial extracellular vesicle production and cargo

Streptococcus mutans is the major microbial etiological agent of dental caries and can adhere to surfaces such as type-I collagen, present in dentin and periodontal tissues. Recent studies have characterized planktonic S. mutans bacterial extracellular vesicles (bEVs) and demonstrated environmental-induced changes due to sugar presence or pH alterations. However, to date there are no studies exploring if surface-derived changes - such as tissue glycation - can modulate bEV production in the context of oral biofilm formation in the elderly. Therefore, the aim of this work was to determine the role of biofilm formation and collagen glycation on the morphology and composition of S. mutans bEVs. For this, bEVs from S. mutans biofilms on native and glycated collagen surfaces were isolated, characterized, and compared to bEVs from planktonic cells. Nanoparticle tracking analysis and microscopy confirmed bEV production and showed that bEVs from biofilms are smaller in size and less abundant than those from planktonic cells. Furthermore, proteome analysis revealed that S. mutans biofilm formation on native and glycated collagen led to the enrichment of several key virulence proteins such as Eno, LuxS, Tpx, and ScrB. Also, a shift towards proteins involved in metabolic processes was found in bEVs following biofilm formation on collagen surfaces, whereas glucan metabolism proteins were overexpressed in vesicles from the planktonic state. These results demonstrate that biofilm formation, as well as the glycation of collagen associated with aging and hyperglycemia, can modulate bEV characteristics and cargo and could play a central role in S. mutans virulence and the development of diseases such as dental caries and periodontal disease.

microbiology↗

bioRxiv2021

A δ-cell subpopulation with a pro-β-cell identity confers efficient age-independent recovery in a zebrafish model of diabetes

Restoring damaged {beta}-cells in diabetic patients by harnessing the plasticity of other pancreatic cells raises the questions of the efficiency of the process and of the functionality of the new Insulin-expressing cells. To overcome the weak regenerative capacity of mammals, we used regeneration-prone zebrafish to study {beta}-cells arising following destruction. We show that most new insulin cells differ from the original {beta}-cells as they are Somatostatin+ Insulin+, but are nevertheless functional and normalize glycemia. These bihormonal cells are transcriptionally close to a subset of {delta}-cells in normal islets characterized by the expression of somatostatin 1.1 (sst1.1), the {beta}-cell genes pdx1, slc2a2 and gck, and the machinery for glucose-induced Insulin secretion. {beta}-cell destruction triggers massive sst1.1 {delta}-cell conversion to bihormonal cells. Our work shows that their pro- {beta}-cell identity predisposes this zebrafish {delta}-cell subpopulation to efficient age-independent neogenesis of Insulin-producing cells and provides clues to restoring functional {beta}-cells in mammalian diabetes models.

cell biology↗

bioRxiv2018

Intertwined canonical and non-canonical initiation in dual promoters are pervasive and differentially regulate Polymerase II transcription

The diversity and complexity of transcription start site (TSS) selection reflects variation of preinitiation complexes, divergent function of promoter-binding proteins and underlies not only transcriptional dynamics but may also impact on post-transcriptional fates of RNAs. The majority of metazoan genes are transcribed by RNA polymerase II from a canonical initiation motif having an YR dinucleotide at their TSSs. In contrast, translation machinery-associated genes carry promoters with polypyrimidine initiator (known as 5-TOP or TCT) with cytosine replacing the R nucleotide. The functional significance of start site choice in promoter architectures is little understood. To get insight into the developmental regulation of start site selection we profiled 5 ends of transcripts during zebrafish embryogenesis. We uncovered a novel class of dual-initiation (DI) promoters utilized by thousands of genes. In DI promoters non-canonical YC-initiation representing 5-TOP/TCT initiators is intertwined with canonical YR-initiation. During maternal to zygotic transition, the two initiation types are divergently used in hundreds of DI promoters, demonstrating that the two initiation systems are distinctly regulated. We show via the example of snoRNA host genes and translation interference experiments that dual-initiation from shared promoters can lead to divergent spatio-temporal expression dynamics generating distinct sets of RNAs with different post-transcriptional fates. Thus utilization of DI promoters in large number of genes suggests two transcription initiation mechanisms targeting these promoters. DI promoters are conserved within human and fruit fly and reflect an evolutionary conserved mechanism for switching transcription initiation to adapt to the changing developmental context. Thus, our findings highlight a novel level of complexity of core promoter regulation in metazoans and broaden the scope for identification and characterization of alternative RNA products generated at shared core promoters.

genomics↗