Biology subjects

Jimenez, L.

Publications and source records attributed to Jimenez, L..

At least 19 recordsLinked to original sources

bioRxiv2026

A diverse family of protein antibiotics inhibits the BAM complex by β-signal mimicry

Lectin-like protein antibiotics (Llps) kill Pseudomonas by inhibiting BamA, the essential core of the beta-barrel assembly machinery (BAM). Llps are composed of one or two beta;-lectin domains and a C-terminal peptide, with characterisation to date centred on the two-domain L-type pyocins of P. aeruginosa, which bind BamA extracellular loop 6 and inhibit by delivering the C-terminal peptide to BamA beta;-strand 1. Whether this mechanism is general, and how Llps contend with BamA sequence differences across species, remained unknown. We screened 238 Pseudomonas Llps against 101 genome-sequenced isolates, showing susceptibility across the family is set by BamA extracellular loop 6. Loop 6 length varies, and Llps fall into three targeting modes: short-loop and long-loop specialists and broad-range dual targeters, which have arisen repeatedly. We determine the 2.66 angstrom cryo-electron microscopy structure of a two-domain LlpA bound to BAM, showing recognition has been relocated relative to the L-type pyocins, with loop 6 bound by a single face of the N-terminal beta-lectin domain rather than the inter-domain cleft. This explains how single-domain LlpBs retain BamA targeting and why the second lectin domain has been lost at least twice. We show that the BamA inhibition mechanism is shared across Llps, with a hypervariable C-terminal peptide binding BamA beta-strand 1, inhibiting the BAM insertase by mimicking the beta-signal of BamA substrates. Together, these data provide an atlas of Llp diversity and the mechanistic principles for engineering it, identifying Llps as a tuneable, multi-interface scaffold for BAM-directed precision antibacterials against pathogenic Pseudomonas, including economically important plant pathogens.

biochemistry↗

bioRxiv2026

INPP5E interactome reveals novel connections to growth factor signaling

Primary cilia are sensory cell membrane protrusions whose malfunction causes diseases known as ciliopathies. Joubert syndrome (JBTS) is a rare recessive ciliopathy causing brain malformations and kidney cysts, among other manifestations. A key player in JBTS is INPP5E, a ciliary phosphoinositide lipid phosphatase. Although INPP5E regulates ciliary growth factor signaling, the molecular mechanisms remain poorly understood. Herein, we show that a constitutively active growth factor receptor (PDGFR-D842V) stimulates INPP5E tyrosine phosphorylation, as does the SRC tyrosine kinase. INPP5E tyrosine phosphorylation did not affect its enzyme activity but was associated with stronger binding to SH3GL1, an endocytic regulator, and SNX9, a phosphoinositide-binding protein involved, like INPP5E, in growth factor-induced ciliary ectovesicle release. Our INPP5E interactomic studies identified other growth factor signaling regulators, including among others: SIN1 (the phosphoinositide-binding subunit of the mTORC2 complex), STRAP (a TGF{beta} and PI3K/AKT signaling regulator), GRB2 (a growth factor receptor adaptor) and the JBTS-associated proteins AHI1 and NPHP1. Moreover, INPP5E strongly interacted with the phosphopeptide-binding 14-3-3 proteins, and did so only in presence of serine-85, a phosphorylated INPP5E residue. Lastly, we found that INPP5E differentially regulates two cilium-dependent growth factor signaling pathways in fibroblasts. Thus, while INPP5E downregulated PDGF-induced AKT phosphorylations, it upregulated TGF{beta}-induced SMAD2 and ERK phosphorylations. Altogether, our work provides important clues on the cilia-dependent actions of growth factors, with implications for ciliopathies like JBTS.

biochemistry↗

bioRxiv2025

Genomes of ancient asexual mites appear streamlined in their architecture

The long-term persistence of obligate asexual lineages represents one of the most enduring and critical paradoxes in evolutionary biology. Sexual reproduction, through meiotic recombination and segregation, enables the efficient removal of deleterious mutations and facilitates rapid adaptation to shifting environmental pressures. Lineages that lose sex are therefore classically predicted to experience genomic decay and face rapid extinction. Oribatid mites (Acari, Sarcoptiformes) represent a unique system for testing these predictions, as they feature multiple, ancient, and independent transitions to asexuality, providing a natural experiment on the evolutionary fate of asexual genomes. We compared four sets of sister sexual and asexual species using high-quality nuclear genome assemblies to investigate the genomic consequences of long-term asexuality. Our study revealed a profound, reproductive-mode-dependent dichotomy in the evolution of genome architecture. Contrary to their expected genomic decay, asexual species have mostly streamlined genomes with less novel genes than their sexual sister species. In contrast, sexual species have acquired genetic innovations, encompassing both gene and transposable element content. These results challenge classical expectations of genomic deterioration in asexual species and might explain the long-term evolutionary persistence of oribatid mites.

genomics↗

bioRxiv2025

Flavobacteria buffer nitrous oxide emissions from partial denitrifiers in coastal sediments

Nearly one-fifth of global emissions of the potent greenhouse gas nitrous oxide (N2O) originate from the ocean, particularly from nutrient-polluted coastal regions. Permeable (sandy) sediments, which cover half of the continental shelf worldwide, are potential sources of N2O due to increasing nutrient inputs from urbanization and agriculture. Yet, the microbial processes determining N2O emissions in these dynamic and unique ecosystems remain understudied. Here, we combined environmental measurements, bacterial cultivation, and genomic analyses to understand the microbes and processes controlling N2O cycling in permeable sediments from Port Phillip Bay (Australia). We established a genomic resource comprising 249 metagenome-assembled genomes and 95 new isolate genomes. Genome-based metabolic reconstructions and culture-based gas measurements revealed diverse bacteria in these sediments produce N2O through incomplete denitrification pathways. However, these bacteria co-occurred with highly abundant clade II N2O-reducing bacteria from the Flavobacteriaceae family. Kinetic profiling revealed both clade II nosZ flavobacterial isolates and whole sand communities exhibit a low affinity for N2O, contrary to previous reports that clade II N2O reducers generally have a high substrate affinity. This indicates adaptation to the high residence times of N2O within production and consumption zones in the sands. Collectively, these N2O reducers remove most N2O produced in permeable sediments, supporting lower-than-expected coastal emissions predicted by biogeochemical models. We conclude that permeable sediments host specialised microbial communities that mitigate N2O emissions and buffer marine nitrogen cycling amid rising nutrient pollution.

microbiology↗

bioRxiv2025

Ultraconserved elements coupled with machine learning approaches resolve the systematics in model nematode species

Nematodes are among the most diverse animals, yet only around 28,000 of an estimated one million species have been morphologically described. Their small size, morphological simplicity, and cryptic diversity complicate phylogenetic analyses. Traditional morphological and single-locus molecular approaches often lack resolution for both recent and ancient divergences. To address these limitations, we developed the first ultraconserved elements (UCEs) probe sets for two nematode families: Panagrolaimidae, a group of non-model organisms with limited genomic resources when compared to model taxa, and Rhabditidae, which includes the model species Caenorhabditis elegans. Our probe sets targeted 1,612 loci for Panagrolaimidae and 100,397 for Rhabditidae. In vitro testing recovered up to 1,457 loci in Panagrolaimidae, supporting robust phylogenetic reconstruction. Results were largely consistent with previous analyses, except for one strain reclassified as Neocephalobus halophilus BSS8. Using machine learning, we determined the minimum number of loci needed for accurate genus-level classification. For Rhabditidae, XGBoost achieved high accuracy with just 46 loci. For Panagrolaimidae, 39 loci were most informative. Our UCE-based approach offers a scalable and cost-effective framework for phylogenomics, enhancing taxonomic resolution and evolutionary inference in nematodes. It is well suited for biodiversity assessments and shallow, field-based sequencing, expanding research possibilities across this ecologically important phylum.

evolutionary biology↗

bioRxiv2025

Metabolically flexible microorganisms rapidly establish glacial foreland ecosystems

An overriding question in ecology is how new ecosystems form. This question can be tested by studying colonisation of environments with little to no pre-existing life. Here, we investigated the functional basis of microbial colonisation in the forelands of a maritime Antarctic and an alpine Swiss retreating glacier, by integrating quantitative ecology, genome-resolved metagenomics, and biogeochemical measurements. Habitat generalists and opportunists rapidly colonize both forelands and persist across soil depth and decadal chronosequences that serve as proxies for temporal community dynamics. These microbes are metabolically flexible chemotrophic aerobes that overcome oligotrophic conditions by using both organic and inorganic compounds, including atmospheric trace gases and sulfur substrates, for energy and carbon acquisition. They co-exist with metabolically flexible early-colonising opportunists and metabolically restricted later-colonising specialists, including photosynthetic Cyanobacteria, ammonia-oxidising archaea, and obligate predatory and symbiotic bacteria, that exhibit narrower habitat distributions. Analysis of 589 species-level metagenome-assembled genomes reveals early colonisation both by generalists and opportunists is strongly associated with metabolic flexibility. Field- and laboratory-based biogeochemical measurements reveal the activity of metabolically flexible microbes rapidly commenced in the forelands. Altogether, these findings suggest primary succession in glacial foreland soils is driven by self-sufficient metabolically flexible bacteria that mediate chemosynthetic primary production and likely provide a more hospitable soil environment for subsequent colonisation.

microbiology↗

bioRxiv2024

The inhibition of three distinct signaling pathways eliminates the oncogenic Tribbles homolog 2 from melanoma cells

Tribbles homolog 2 (TRIB2) is one of three members of the Tribbles family of pseudo serine/threonine kinases. It acts as an oncogene whose expression is correlated with tumor progression and therapy resistance in melanoma. TRIB2 has been implicated in conferring resistance to various anti-cancer therapies suggesting TRIB2 as a therapeutic target for resistant tumors. This study explores the pharmacological targeting of TRIB2, revealing several independent routes of pharmacological manipulations. TRIB2 is a short-lived protein stabilized by inhibition of the PI3K/AKT pathway. Conversely, inhibitors of BRAF, MEK and ERK significantly decrease TRIB2 expression by a mechanism that involves transcription. Additionally, Polo-Like Kinases (PLKs) inhibitors significantly reduce TRIB2 protein expression and stability. Strikingly, increasing concentrations of the kinase inhibitor PIK-75 effectively eliminate TRIB2 in melanoma cells surpassing its PI3K inhibitory activity suggesting the destabilizing effect of the inhibition of an unknown kinase. TMT-based proteomics, chemical biology and genetic manipulation revealed CDK12 as the kinase that mediates the destabilizing effect on TRIB2. Overall, we identify three distinct classes of compounds that efficiently eliminate the oncogenic TRIB2 protein from melanoma cells based on different molecular mechanisms and exhibiting 40 to 200 times greater potency than the previously reported afatinib.

cancer biology↗

bioRxiv2023

An obligate aerobe adapts to hypoxia by hybridising fermentation with carbon storage

In soil ecosystems, obligately aerobic bacteria survive oxygen deprivation (hypoxia) by entering non-replicative persistent states. Little is known about how these bacteria rewire their metabolism to stay viable in these states. The model obligate aerobe Mycobacterium smegmatis maintains redox homeostasis during hypoxia by mediating fermentative hydrogen production. However, the fate of organic carbon during fermentation, and the associated remodeling of carbon metabolism, is unresolved. Here we systematically profiled the metabolism of M. smegmatis during aerobic growth, hypoxic persistence, and the transition between these states. Using differential isotope labelling, and paired metabolomics and proteomics, we observed rerouting of central carbon metabolism through the pentose phosphate pathway and Entner-Doudoroff pathway during hypoxia. We show that M. smegmatis excretes high levels of hydrogen concurrently with upregulating triacylglyceride synthases and accumulating glycerides as carbon stores. Using electron cryotomography (cryo-ET), we observed the presence of large spheroid structures consistent with the appearance of lipid droplets. Thus, in contrast to obligately and facultative anaerobic fermentative bacteria, M. smegmatis stores rather than excretes organic carbon during hypoxia. This novel hybrid metabolism likely provides a competitive advantage in resource-variable environments by allowing M. smegmatis to simultaneously dispose excess reductant during hypoxia and maintain carbon stores to rapidly resume growth upon reoxygenation.

microbiology↗

bioRxiv2023

Culture conditions greatly impact the levels of vesicular and extravesicular Ago2 and RNA in extracellular vesicle preparations.

Extracellular vesicle (EV)-carried miRNAs can influence gene expression and functional phenotypes in recipient cells. Argonaute 2 (Ago2) is a key miRNA-binding protein that has been identified in EVs and could influence RNA silencing. However, Ago2 is in a non-vesicular form in serum and can be an EV contaminant. In addition, RNA-binding proteins (RBPs), including Ago2, and RNAs are often minor EV components whose sorting into EVs may be regulated by cell signaling state. To determine the conditions that influence detection of RBPs and RNAs in EVs, we evaluated the effect of growth factors, oncogene signaling, serum, and cell density on the vesicular and nonvesicular content of Ago2, other RBPs, and RNA in small EV (SEV) preparations. Media components affected both the intravesicular and extravesicular levels of RBPs and miRNAs in EVs, with serum contributing strongly to extravesicular miRNA contamination. Furthermore, isolation of EVs from hollow fiber bioreactors revealed complex preparations, with multiple EV-containing peaks and a large amount of extravesicular Ago2/RBPs. Finally, KRAS mutation impacts the detection of intra- and extra-vesicular Ago2. These data indicate that multiple cell culture conditions and cell states impact the presence of RBPs in EV preparations, some of which can be attributed to serum contamination.

cancer biology↗

bioRxiv2023

Therapy Development for Microvillus Inclusion Disease using Patient-derived Enteroids

Microvillus Inclusion Disease (MVID), caused by loss-of-function mutations in the motor protein Myosin Vb (MYO5B), is a severe infantile disease characterized by diarrhea, malabsorption, and acid-base instability, requiring intensive parenteral support for nutritional and fluid management. Human patient-derived enteroids represent a model for investigation of monogenic epithelial disorders but are a rare resource from MVID patients. We developed human enteroids with different loss-of function MYO5B variants and showed that they recapitulated the structural changes found in native MVID enterocytes. Multiplex Immunofluorescence imaging of patient duodenal tissues revealed patient-specific changes in localization of brush border transporters. Functional analysis of electrolyte transport revealed profound loss of Na+/H+ exchange (NHE) activity in MVID patient enteroids with near-normal chloride secretion. The chloride channel-blocking anti-diarrheal drug, Crofelemer, dose-dependently inhibited agonist-mediated fluid secretion. MVID enteroids exhibited altered differentiation and maturation versus healthy enteroids. Inhibition of Notch signaling with the {gamma}-secretase inhibitor, DAPT, recovered apical brush border structure and functional Na+/H+ exchange activity in MVID enteroids. Transcriptomic analysis revealed potential pathways involved in the rescue of MVID cells including serum- and glucocorticoid-induced protein kinase 2 (SGK2), and NHE regulatory factor 3 (NHERF3). These results demonstrate the utility of patient-derived enteroids for developing therapeutic approaches to MVID. Conflict-of-interest statementThe authors have declared that no conflict of interest exists.

cell biology↗

bioRxiv2022

A comparison of survey method efficiency for estimating densities of Zebra Mussels (Dreissena polymorpha)

Abundance surveys are a common and practical technique to estimate plant or animal densities. Methods used to conduct these surveys often require jointly estimating uncertainty in both counts and detection probability. The estimation of detection probability requires additional measurements that take time, potentially reducing the efficiency of the survey for high-density populations. We conducted quadrat, removal, and distance surveys of zebra mussels (Dreissena polymorpha) in three central Minnesota lakes and used an efficiency measure to help compare survey designs. Survey efficiency depended on both the survey design and the population density. The efficiency of survey designs that required estimates of detection probabilities (relative to designs that did not) decreased with density, leading to a change in the most efficient survey design at high densities. These results demonstrate that the best survey design may be context-specific, requiring some prior knowledge of the underlying population density and the cost/time needed to collect additional information for estimating detection probabilities.

ecology↗

bioRxiv2022

Atmospheric hydrogen oxidation extends to the domain archaea

Diverse aerobic bacteria use atmospheric hydrogen (H2) and carbon monoxide (CO) as energy sources to support growth and survival. Though recently discovered, trace gas oxidation is now recognised as a globally significant process that serves as the main sink in the biogeochemical H2 cycle and sustains microbial biodiversity in oligotrophic ecosystems. While trace gas oxidation has been reported in nine phyla of bacteria, it was not known whether archaea also use atmospheric H2. Here we show that a thermoacidophilic archaeon, Acidianus brierleyi (Thermoproteota), constitutively consumes H2 and CO to sub-atmospheric levels. Oxidation occurred during both growth and survival across a wide range of temperatures (10 to 70{degrees}C). Genomic analysis demonstrated that A. brierleyi encodes a canonical carbon monoxide dehydrogenase and, unexpectedly, four distinct [NiFe]-hydrogenases from subgroups not known to mediate aerobic H2 uptake. Quantitative proteomic analyses showed that A. brierleyi differentially produced these enzymes in response to electron donor and acceptor availability. A previously unidentified group 1 [NiFe]-hydrogenase, with a unique genetic arrangement, is constitutively expressed and upregulated during stationary phase and aerobic hydrogenotrophic growth. Another archaeon, Metallosphaera sedula, was also found to oxidize atmospheric H2. These results suggest that trace gas oxidation is a common trait of aerobic archaea, which likely plays a role in their survival and niche expansion, including during dispersal through temperate environments. These findings also demonstrate that atmospheric H2 consumption is a cross-domain phenomenon, suggesting an ancient origin of this trait, and identify previously unknown microbial and enzymatic sinks of atmospheric H2 and CO.

microbiology↗

bioRxiv2022

Extracellular vesicles from non-neuroendocrine SCLC cells promote adhesion and survival of neuroendocrine SCLC cells

Small Cell Lung Cancer (SCLC) tumors are made up of distinct cell subpopulations, including neuroendocrine (NE) and non-NE cells. While secreted factors from non-NE SCLC cells have been shown to support the growth of the NE cells, the underlying molecular factors are not well understood. Here, we show that exosome-type small extracellular vesicles (SEVs) secreted from non-NE SCLC cells promote adhesion and survival of NE SCLC cells. Proteomic analysis of purified small EVs revealed that extracellular matrix (ECM) proteins and integrins are highly enriched in small EVs of non-NE cells whereas nucleic acid-binding proteins are enriched in small EVs purified from NE cells. Addition of select purified ECM proteins identified in purified EVs, specifically fibronectin, laminin 411, and laminin 511, were able to substitute for the role of non-NE-derived SEVs in promoting adhesion, survival, and tumorigenicity of NE SCLC cells. Those same proteins were differentially expressed by human SCLC subtypes. These data suggest that ECM-carrying SEVs secreted by non-NE cells play a key role in supporting SCLC tumor growth and survival.

cancer biology↗

bioRxiv2022

A new method to estimate the ecological niche through n-dimensional hypervolumes that combines convex hulls and elliptical envelopes

O_LIMethods that estimate the niche of a species by calculating a convex hull or an elliptical envelope have become popular due to their simplicity and interpretation, given Hutchinsons conception of the niche as an n-dimensional hypervolume. C_LIO_LIIt is well known that convex hulls are sensitive to outliers and do not have the ability to differentiate between regions of low and high concentration of presences, while the elliptical envelopes may contain large regions of niche space that are not relevant for the species. Thus, when the goal is to estimate the realized niche of the species, both methods may overestimate the niche. C_LIO_LIWe present a methodology that combines both the convex hull and the elliptical envelope methods producing an n-dimensional hypervolume that better fits the observed density of species presences, making it a better candidate to model the realized niche. Our method, called the CHE approach, allows defining regions of iso-suitability as a function of the significance levels inherited from the method (Mahalanobis distance model, minimum covariance determinant, or minimum volume ellipsoid) used to fit an initial elliptical envelope from which we then discard regions not relevant for the species by calculating a convex hull. C_LIO_LIWe applied the CHE approach to a case study of twenty-five species of bats present in the Iberian Peninsula, fitting a hypervolume for each species and comparing them to both the convex hulls and elliptical envelopes obtained with the same data and different values of n. We show that as the number of variables used to define the niche space increases, both the convex hull and elliptical envelope models produce overly large hypervolumes, while the size of the hypervolume fitted with the CHE approach remains stable. As a consequence, similarity measures that account for the niche overlap among different species may be inflated when using convex hulls or elliptical envelopes to model the niche; something that does not occur under the CHE approach. C_LI

ecology↗

bioRxiv2020

Geographic potential of the world largest hornet, Vespa mandarinia Smith (Hymenoptera: Vespidae), worldwide and particularly in North America

The Asian giant hornet (AGH, Vespa mandarinia) is the worlds largest hornet, occurring naturally in the Indomalayan region, where it is a voracious predator of pollinating insects including honey bees. In September 2019, a nest of Asian giant hornets was detected outside of Vancouver, British Columbia and in May 2020 an individual was detected nearby in Washington state, indicating that the AGH successfully overwintered in North America. Because hornets tend to spread rapidly and become pests, reliable estimates of the potential invasive range of V. mandarinia in North America are needed to assess likely human and economic impacts, and to guide future eradication attempts. Here, we assess climatic suitability for AGH in North America, and suggest that, without control, this species could establish populations across the Pacific Northwest and much of eastern North America. Predicted suitable areas for AGH in North America overlap broadly with areas where honey production is highest, as well as with species-rich areas for native bumble bees and stingless bees of the genus Melipona in Mexico, highlighting the economic and environmental necessity of controlling this nascent invasion.

ecology↗

bioRxiv2019

On Some Problems of Estimating Fundamental Niche from Physiological Data

Hutchinson proposed the idea of the fundamental niche, determined by physiological properties of a species, more than 50 years ago. The idea remains both central to ecological thinking and largely unexplored experimentally. In this note, we describe some problems of using physiological experiments databases to estimate fundamental niches, show some solutions, and the apply our solution to testing the prediction that fundamental niches contain realized niches, for some species of marine fishes and terrestrial beetles. Our results were concordant with Hutchinsons predictions.

ecology↗

bioRxiv2019

Progressive shifts in the gut microbiome reflect prediabetes and diabetes development in a treatment-naive Mexican cohort

Type 2 diabetes (T2D) is a global epidemic that affects more than 8% of the worlds population and is a leading cause of death in Mexico. Diet and lifestyle are known to contribute to the onset of T2D. However, the role of the gut microbiome in T2D progression remains uncertain. Associations between microbiome composition and diabetes are confounded by medication use, diet, and obesity. Here we present data on a treatment-naive cohort of 405 Mexican individuals across varying stages of T2D severity. Associations between gut bacteria and more than 200 clinical variables revealed a defined set of bacterial genera that were consistent biomarkers of T2D prevalence and risk. Specifically, gradual increases in blood glucose levels, beta cell dysfunction, and the accumulation of measured T2D risk factors was correlated with the relative abundances of four bacterial genera. In a cohort of 25 individuals, T2D treatment - predominantly metformin - reliably returned the microbiome to the normoglycemic community state. Deep clinical characterization allowed us to broadly control for confounding variables, indicating that these microbiome patterns were independent of common T2D comorbidities, like obesity or cardiovascular disease. Thus, our work provides the first solid evidence for a direct link between the gut microbiome and T2D in a critically high-risk population. Whether or not these T2D-associated changes in the gut contribute to the etiology of T2D or its comorbidities remains to be seen.

systems biology↗

bioRxiv2018

Host sexual dimorphism affects the outcome of within-host pathogen competition

Natural infections often consist multiple pathogens of the same or different species. In multiple infections, pathogens compete for access to host resources and fitness is determined by how well a pathogen can reproduce compared to its competitors. Given the propensity for males and females to exhibit variation in pathogen-induced reduction in lifespan or fecundity, we explore how host sex may modulate the competitive ability of pathogens, potentially favouring the transmission of different pathogen genotypes. Using the Daphnia magna - Pasteuria ramosa model system, we exposed male and female hosts to either a single genotype infection or coinfections consisting of two pathogen genotypes of varying levels of virulence, measured as pathogen-induced reduction in host lifespan. We found that co-infections within females generally favoured the transmission of the more virulent pathogen genotype. Conversely, co-infections within male hosts resulted in equal transmission of competing genotypes, or favoured the transmission of the less virulent pathogen genotype in treatments where it established prior to the more virulent competitor. These results suggest that sex is a form of host heterogeneity which may influence the evolution of virulence within co-infection contexts and that one sex may be a reservoir for pathogen genetic diversity in nature.

evolutionary biology↗