Biology subjects

Gonzalez-Juarbe, N.

Publications and source records attributed to Gonzalez-Juarbe, N..

10 recordsLinked to original sources

bioRxiv2026

The Vagus Nerve conducts viable translocation of gut flora to the lungs that impacts interstitial lung disease severity in mice

Communication between gut microbiota and extraintestinal organs is increasingly recognized, yet elucidation of relevant translocation mechanism(s) remains enigmatic. Vagus neuroanatomy and reports of vagal protein transfer to extraintestinal organs suggest that this "superhighway" could translocate bacteria. Here we explore whether the vagus superhighway can translocate bacteria to extraintestinal organs. Gavage of green fluorescent protein-expressing Escherichia coli (GFP-E. coli) into germ-free (GF) or specific-pathogen free (SPF) C57BL/6 mice yielded high bacillary loads in the stomach and lungs, followed by the heart, stool and peripheral muscles, despite negative blood cultures. Notably, confocal microscopy and culture revealed GFP-E. coli within the vagus nerve within five minutes of gavage suggesting rapid translocation. Metagenomic analysis of stool, lung, heart, vagus nerve, and muscle from non-gavaged SPF mice demonstrated significant microbial overlap, supporting that bacterial translocation occurs despite the presence of endogenous microflora. Remarkably, subdiaphragmatic vagotomy performed prior to GFP-E. coli gavage resulted in marked reductions of bacterial transduction in the lungs and other extraintestinal organs, except muscle. Furthermore, vagotomy significantly reduced lung fibrosis in SPF mice following intranasal bleomycin administration. In lung cancer patients undergoing lobectomy, vagotomy inhibited postsurgical reductions in forced vital capacity. These findings identify the vagus nerve as a literal gut-lung axis, facilitating viable bacterial translocation and influencing lung severity.

microbiology↗

bioRxiv2026

A Triple-Modality Peptide-Antibiotic-Phage Therapy Eradicates Multidrug-Resistant Serratia marcescens Biofilms

Serratia marcescens is an opportunistic pathogen that causes severe hospital-acquired infections, notable for its biofilm formation abilities and development of extensive antibiotic resistance. Here we evaluated the efficacy of bacteriophages, antibiotics, and antimicrobial peptides (BAP), alone and in combination, against fourteen multi-drug-resistant (MDR) S. marcescens isolates sourced from hospitals and other environmental settings in an in vitro biofilm model. Phage combination with a cocktail of sub-minimal inhibitory concentration (MIC) of penicillin-streptomycin, kanamycin, and ciprofloxacin, reduced biofilm biomass, however, complete decolonization was not achieved. Incorporating an antimicrobial peptide cocktail into this regimen eradicated 99.99% of multi-drug-resistant isolates grown planktonically or in surface-associated biofilms. Microscopy and viability assays confirmed extensive biofilm disruption and bacterial clearance without regrowth. These findings reveal that simultaneous interference of cell wall synthesis, protein translation, DNA replication, and membrane integrity can overcome S. marcescens antimicrobial defenses, establishing a multifaceted therapeutic framework for managing device-associated infections caused by MDR pathogens.

microbiology↗

bioRxiv2026

Biological signatures of history: Examination of composite biomes and Y chromosome analysis from da Vinci-associated cultural artifacts

Cultural heritage objects can accumulate DNA from materials, environments, and repeated human contact, but biomolecular profiling of such items is constrained by nondestructive sampling requirements, ultra-low biomass, and high contamination risk. Here we present a minimally invasive workflow that integrates gentle swab collection, low- input whole-metagenome sequencing, taxonomic profiling, and Y-chromosome analyses to recover "biological signatures of history" from Renaissance-era artwork and archival correspondence associated with ancestors of Leonardo da Vinci. Across artifacts, we recovered heterogeneous mixtures of microbial and eukaryotic DNA (including bacteria, fungi, plants, and viruses) consistent with composite "biomes" that reflect differences in substrate, storage, conservation treatments, and handling. Multivariate comparisons show reproducible sample-to-sample separations. In parallel, we assessed human Y-chromosome signal using a panel of [~]90,000 phylogenetically informative markers and partial Y-STR profiling where feasible. Across multiple independent swabs from Leonardo da Vinci-associated items, the obtained Y chromosome marker data suggested assignments withing the broader E1b1/E1b1b clade. However, the control samples also indicate mixed contributions consistent with modern handling and other sources. Together, these data demonstrate the feasibility as well as limitations of combining metagenomics and human DNA marker analysis for cultural heritage science, providing a baseline workflow for future conservation science studies and hypothesis-driven investigations of provenance, authentication and handling history.

genomics↗

bioRxiv2025

Respiratory exposure to inert particulate matter during pregnancy leads to oxidative stress and cardiac proteome remodeling

Withdrawal StatementThe authors have withdrawn this manuscript because upon peer review major revisions have been identified as needed to ensure that the conclusions are in par with the presented data. Current studies are ongoing to provide a more complete version of the manuscript for peer review publication. Therefore, the authors do not wish this work to be cited as reference for the project in its current form. If you have any questions, please contact the corresponding author.

molecular biology↗

bioRxiv2024

Multiomic Insights into Human Health: Gut Microbiomes of Hunter-Gatherer, Agropastoral, and Western Urban Populations

Societies with exposure to preindustrial diets exhibit improved markers of health. Our study used a comprehensive multi-omic approach to reveal that the gut microbiome of the Ju/hoansi hunter-gatherers, one of the most remote KhoeSan groups, exhibit a higher diversity and richness, with an abundance of microbial species lost in the western population. The Ju/hoansi microbiome showed enhanced global transcription and enrichment of complex carbohydrate metabolic and energy generation pathways. The Ju/hoansi also show high abundance of short-chain fatty acids that are associated with health and optimal immune function. In contrast, these pathways and their respective species were found in low abundance or completely absent in Western populations. Amino acid and fatty acid metabolism pathways were observed prevalent in the Western population, associated with biomarkers of chronic inflammation. Our study provides the first in-depth multi-omic characterization of the Ju/hoansi microbiome, revealing uncharacterized species and functional pathways that are associated with health.

genomics↗

bioRxiv2024

Sampling Techniques and Genomic Analysis of Biological Material from Artworks

The genomic analysis of biological material obtained from artwork or cultural heritage artifacts can be used to guide curation, preservation and restoration. However, the recovery of biological samples from artworks is dependent on the sampling technique used and the media from which the biological materials are recovered. The ideal sampling method should be non-invasive, yet robust. Only rare examples of direct comparisons among sampling techniques have been reported. To develop a framework for the recovery of biological samples for subsequent microbial DNA analysis, we studied five artworks on paper and compared three sampling methods, each with increasing degrees of invasiveness. Minimally invasive swabbing techniques collect samples from the surface, whereas more aggressive techniques such as wet vacuuming were expected to yield more biological material from within the support media. We report a comparison of collection techniques to generate microbial DNA sequence data from artworks on paper. We observed that wet vacuuming resulted in higher DNA recovery than double swabbing and core punches; however, all three techniques yielded satisfactory microbial DNA sequences. Diverse microbial populations existed to varying degrees on the corners and centers of the five artworks studied, but the distribution of the total biomass was relatively even across the surfaces of the works sampled. Studies of peripheral regions, where sampling is less likely to cause alterations to the artwork, could thus yield useful results in microbiome studies. These results provide a framework for sampling artworks on paper to obtain biological material for microbial genomic analysis. The methods described may provide microbiome identification to facilitate restoration and preservation, and might also contribute to the determination of provenance.

genetics↗

bioRxiv2023

SARS-CoV-2 ORF8 modulates lung inflammation and clinical disease progression

The virus severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, is the causative agent of the current COVID-19 pandemic. It possesses a large 30 kilobase (kb) genome that encodes structural, non-structural, and accessory proteins. Although not necessary to cause disease, these accessory proteins are known to influence viral replication and pathogenesis. Through the synthesis of novel infectious clones of SARS-CoV-2 that lack one or more of the accessory proteins of the virus, we have found that one of these accessory proteins, ORF8, is critical for the modulation of the host inflammatory response. Mice infected with a SARS-CoV-2 virus lacking ORF8 exhibit increased weight loss and exacerbated macrophage infiltration into the lungs. Additionally, infection of mice with recombinant SARS-CoV-2 viruses encoding ORF8 mutations found in variants of concern reveal that naturally occurring mutations in this protein influence disease severity. Our studies with a virus lacking this ORF8 protein and viruses possessing naturally occurring point mutations in this protein demonstrate that this protein impacts pathogenesis. SignificanceSince its emergence in 2019, SARS-CoV-2 has accrued mutations throughout its 30kb genome. Of particular interest are the mutations present in the ORF8 protein, which occur in every major variant. The precise function and impact of this protein on disease severity and pathogenesis remains understudies. Our studies reveal that the ORF8 protein modulates the immune response by impacting macrophage infiltration into the lungs. Additionally, we have shown that the ORF8 protein of SARS-CoV-2 has accrued mutations throughout its evolution that lead to a loss of function phenotype in this protein. Our work reveals that the ORF8 protein of SARS-CoV-2 contributes significantly to disease progression through modulation of the inflammatory response.

microbiology↗

bioRxiv2022

A multiomics analysis of direct interkingdom dynamics between influenza A virus and Streptococcus pneumoniae uncovers host-independent changes to bacterial virulence fitness

BackgroundFor almost a century, it has been recognized that influenza A virus (IAV) infection can promote the development of secondary bacterial infections (SBI) mainly caused by Streptococcus pneumoniae (Spn). Recent observations have shown that IAV is able to directly bind to the surface of Spn. To gain a foundational understanding of how direct IAV-Spn interaction alters bacterial biological fitness we employed combinatorial multi-omic and molecular approaches. ResultsHere we show IAV significantly remodels the global transcriptome, proteome and phosphoproteome profiles of Spn independently of host effectors. We identified Spn surface proteins that interact with IAV proteins (hemagglutinin, nucleoprotein, and neuraminidase). In addition, IAV was found to directly modulate expression of Spn virulence determinants such as pneumococcal surface protein A, pneumolysin, and factors associated with antimicrobial resistance among many others. Metabolic pathways were significantly altered leading to changes in Spn growth rate. IAV was also found to drive Spn capsule shedding and the release of pneumococcal surface proteins. Released proteins were found to be involved in evasion of innate immune responses and actively reduced human complement hemolytic and opsonizing activity. IAV also led to phosphorylation changes in Spn proteins associated with metabolism and bacterial virulence. Validation of proteomic data showed significant changes in Spn galactose and glucose metabolism. Furthermore, supplementation with galactose rescued bacterial growth and promoted bacterial invasion, while glucose supplementation led to enhanced pneumolysin production and lung cell apoptosis. ConclusionsHere we demonstrate that IAV can directly modulate Spn biology without the requirement of host effectors and support the notion that inter-kingdom interactions between human viruses and commensal pathobionts can promote bacterial pathogenesis and microbiome dysbiosis.

microbiology↗

bioRxiv2020

The global proteome and phosphoproteome landscape of sepsis-induced kidney injury

Sepsis-induced acute kidney injury (S-AKI) is the most common complication in hospitalized and critically ill patients, highlighted by a rapid decline of kidney function occurring a few hours or days after sepsis onset. Systemic inflammation elicited by microbial infections is believed to lead to kidney damage under immunocompromised conditions. However, while AKI has been recognized as a disease with long-term sequelae, partly due to the associated higher risk of chronic kidney disease (CKD), the understanding of kidney pathophysiology at the molecular level and the global view of dynamic regulations in situ after S-AKI, including transition to CKD, remains limited. Existing studies of S-AKI mainly focus on deriving sepsis biomarkers from body fluids. In the present study, we constructed a mid-severity septic murine model using cecal ligation and puncture (CLP), and examined the temporal changes to the kidney proteome and phosphoproteome at day 2 and day 7 after CLP surgery, corresponding to S-AKI and the transition to CKD, respectively by employing an ultrafast and economical filter-based sample processing method combined with the label-free quantitation approach. Collectively, we identified 2,119 proteins and 2,950 phosphosites through multi-proteomics analyses. Here we denote the pathways that are specifically responsive to S-AKI and its transition to CKD, which include regulation of cell metabolism regulation, oxidative stress, and energy consumption in the diseased kidneys. Our data can serve as an enriched resource for the identification of mechanisms and biomarkers for sepsis-induced kidney diseases.AbbreviationsAKIAcute kidney injuryBADBcl2-associated agonist of cell death proteinCKDChronic kidney diseaseCLPCecal ligation and punctureDAMPsDamage-associated molecular patternsELISAEnzyme-linked immunosorbent assayESCRTEndosomal sorting complexes required for transportFADDFAS-associated death domain proteinFCFold changeFDRFalse discovery rateGOGene OntologyGsdmdGasdermin DICUIntensive care unitKEGGKyoto Encyclopedia of Genes and GenomesLFQLabel-free quantitationNGALNeutrophil gelatinase-associated lipocalin proteinPAMPsPathogen-associated molecular patternsPASPeriodic acid-SchiffPCAPrinciple component analysisS-AKISepsis-induced acute kidney injurySLCSolute carrier proteinsSTrapSuspension TrappingTLRsToll-like receptorsView Full Text

pathology↗

bioRxiv2020

Influenza-induced oxidative stress sensitizes lung cells to bacterial toxin-mediated necroptosis

RationalePneumonia caused by Influenza A virus (IAV) co- and secondary bacterial infections are characterized by their severity. Previously we have shown that pore-forming toxin (PFT)-mediated necroptosis is a key driver of acute lung injury during bacterial pneumonia. Here, we evaluate the impact of IAV on PFT-induced acute lung injury during co- and secondary Streptococcus pneumoniae (Spn) infection. ObjectivesDetermine the impact of IAV infection on bacterial PFT-mediated lung epithelial cell (LEC) necroptosis. Determine the molecular basis for increased sensitivity and if inhibition of necroptosis or oxidative stress blocks IAV sensitization of LEC to PFT. MethodsMice and cells were challenged with IAV followed by Spn. Necroptosis was monitored by measuring cell death at fixed time points post-infection and immunofluorescent detection of necroptosis. Wildtype mice and LEC were treated with necroptosis inhibitors. Necroptosis effector molecule MLKL deficiency was tested for infection synergy. Oxidative damage to DNA and lipids as result of infection was measured in vitro and in vivo. Necroptosis and anti-oxidant therapy efficacy to reduce disease severity was tested in vivo. Measurements and Main ResultsIAV synergistically sensitized LEC for PFT-mediated necroptosis in vitro and in murine models of Spn co-infection and secondary infection. Pharmacological induction of oxidative stress sans virus sensitized cells for PFT-mediated necroptosis. Necroptosis inhibition reduced disease severity during secondary bacterial infection. ConclusionsIAV-induced oxidative stress sensitizes LEC for PFT-mediated necroptosis. This is a new molecular explanation for severe influenza-associated bacterial infections. Necroptosis inhibitors are potential therapeutic strategies to reduce IAV-primed bacterial pneumonia severity. SummaryHere we demonstrate that Influenza A virus (IAV) infection synergistically sensitizes lung cells to bacterial pore-forming toxin (PFT)-mediated necroptosis. Moreover, this contributes to the severity of lung injury that is observed during co- and secondary infection with Streptococcus pneumoniae. IAV-induced oxidative stress was identified as a key factor contributing to cell sensitization and induction of oxidative stress sans virus was sufficient to synergistically enhance susceptibility to PFT-mediated killing. Our results advance our understanding on the molecular basis of co- and secondary bacterial infection to influenza and identifies necroptosis inhibition and antioxidant therapy as potential intervention strategies.

microbiology↗