Biology subjects

Salgado, S.

Publications and source records attributed to Salgado, S..

5 recordsLinked to original sources

bioRxiv2026

Computational design of blue melanin with peptide motif scaffolding

De novo melanin design seeks to extend natural melanin colors to new, stable colors (blue, purple, green) with sequence-to-color tunability. Natural melanin, polymerized from tyrosine (Y), is a robust pigment with heterogenous molecular weights. Control of melanin size (length) is challenging; thus, only specific colors (yellow to brown) exist in nature. In this work, we describe the design of blue melanin through the polymerization of Y-containing pentapeptides with two key properties: tight packing during peptide assembly and high solubility in aqueous environments. By motif scaffolding a pentapeptide-repeat protein (PRP) with RFdiffusion, we narrowed 160,000 possible combinations to a library of 905 Y-containing pentapeptides with tight packing features. Two of the most soluble designs successfully formed stable blue melanin with {lambda}max absorbing in 615-620 nm, contributed by homogeneous melanin length achieved around 60 Y units. Other designs also formed new colors (purple, green), along with more known colors (red, yellow, brown). We found that blue melanin exhibited thermal stability at an autoclave temperature of 121{degrees}C and photostability of weeks under 600 lux illumination. We also demonstrated the application of blue melanin as an electrophoretic ink. De novo color design from simple peptides could potentially transform how colorants are sourced and produced. Our approach with computational design should also inspire the development of new deep-learning tools to directly predict colors from amino acid sequences.

biochemistry↗

bioRxiv2025

A Descriptive Analysis of Streptococcus suis-Associated Disease in Irish Pigs from 2010 to 2024: Serotypes, Pathology, and Antimicrobial Resistance

Streptococcus suis is a major cause of respiratory and systemic diseases in post-weaned pigs, leading to significant production losses and animal welfare concerns. This study provides the first long-term national level analysis of Streptococcus suis-associated disease (SSAD) in the Republic of Ireland. We examined the pig diagnostic submissions, characterised serotype distribution, antimicrobial susceptibility, and co-infection patterns from 2010 to 2024. The findings confirm that serotypes 9 and 2 or 1/2 were most frequently associated with disease. We observed a significant shift in recent years where serotype 9 has surpassed serotype 2 or 1/2 in number of occurrences. S. suis was frequently co-detected with viral pathogens including porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2, and swine influenza virus (SIV), as well as bacterial pathogens such as Actinobacillus pleuropneumonia and Pasteurella multocida, typically from pneumonic lungs. While resistance to tetracycline and erythromycin was high (44.4% to 65.8%), isolates remained susceptible to first-line beta-lactam antibiotics such as penicillin (7.9% resistance), ampicillin (5.5% resistance) and amoxycillin/clavulanate (0% resistance). The observed heterogeneity between and within herds challenges successful implementation of vaccination and highlights the need for ongoing disease monitoring. These findings provide the first in-depth assessment of SSAD in Irelands pig population which will offer valuable insights for future surveillance efforts, including genomic studies and supporting evidence-based strategies and vaccine selection for controlling S. suis in Irish pig sector.

microbiology↗

bioRxiv2024

Human PC4 supports telomere stability and viability in cells utilizing the alternative lengthening of telomeres mechanism

Cancer cells with an activated Alternative Lengthening of Telomeres (ALT) mechanism elongate telomeres via homology-directed repair. Sustained telomeric replication stress is an essential trigger of ALT activity; however, it can lead to cell death if not properly restricted. By analyzing publicly available data from genome-wide CRISPR KO screenings, we have identified the multifunctional protein PC4 as a novel factor essential for ALT cell viability. Depletion of PC4 using siRNAs results in rapid ALT cell death, while telomerase-positive cells show minimal effects. PC4 depletion induces replication stress and telomere fragility primarily in ALT cells, and increases ALT activity. PC4 binds to telomeric DNA in cells, and its binding is enhanced by telomeric replication stress. Finally, a mutant PC4 with partly impaired single stranded DNA binding activity is capable to localize to telomeres and suppress ALT activity and telomeric replication stress. We propose that PC4 supports ALT cell viability, at least partly, by averting telomere dysfunction. Targeted inhibition of PC4 holds promise for innovative therapies to eradicate ALT cancers.

cancer biology↗

bioRxiv2023

Bdellovibrio's Prey-Independent Growth is Fuelled by Amino Acids as a Carbon Source

Identifying the nutritional requirements and growth conditions of microorganisms is crucial for determining their applicability in industry and understanding their role in clinical ecology. Predatory bacteria such as Bdellovibrio bacteriovorus have emerged as promising tools for combating infections by human bacterial pathogens due to their natural killing features. Bdellovibrios lifecycle occurs inside prey cells, using the cytoplasm as a source of nutrients and energy. However, this lifecycle supposes a challenge when determining the specific uptake of metabolites from the prey to complete the growth inside cells, a process that has not been completely elucidated. Here, following a model-based approach we illuminate the ability of Bdellovibrio bacteriovorus to replicate DNA, increase biomass, and generate adenosine triphosphate (ATP) in an amino acid-based rich media in the absence of prey, keeping intact its predatory capacity. In this culture, we determined the main carbon sources used and their preference, being glutamate, serine, aspartate, isoleucine, and threonine. This study offers new insights into the role of predatory bacteria in natural environments and establishes the basis for developing new Bdellovibrio applications using appropriate metabolic and physiological methodologies.

microbiology↗

bioRxiv2022

Golden Standard: A complete standard, portable, and interoperative MoClo tool for model and non-model bacterial hosts.

Modular cloning assembly has become a benchmark technology in synthetic biology. However, there is a mismatch between its impressive development and the standardization required to promote interoperability between the different systems available. The full development of the field is thus hampered by a surge of oftentimes incompatible organism-specific systems. To overcome these issues, we present Golden Standard (GS), a Type IIS assembly method underpinned by the Standard European Vector Architecture (SEVA). GS unlocks modular cloning applications with any type of microorganism and delivers consistent combinatorial multi-part assembly of standardized genetic elements to create genetic circuits of up to twenty transcription units. Reliance on the Golden Gate syntax renders GS fully compatible with many existing tools and it sets the path towards efficient reusability of available part libraries and assembled TUs. GS was fully validated in terms of DNA assembly performance, portability and phenotype engineering in model and non-model bacteria. In order to facilitate the widespread adoption and future community-driven development of GS, we provide a web-portal featuring: i) a repository of parts and vectors, ii) a SBOLHub for exchange and analysis of constructs and iii) Wizard and Setup tools to guide the design of constructs using stored and user-specific parts.

synthetic biology↗