Biology subjects

Martinez, B.

Publications and source records attributed to Martinez, B..

5 recordsLinked to original sources

bioRxiv2025

Molecular response to the non-lytic peptide bac7 (1-35) triggers disruption of Klebsiella pneumoniae biofilm

Klebsiella pneumoniae is becoming increasingly difficult to treat as multidrug-resistant (MDR) strains become more prevalent. The formation of biofilm heightens this threat by embedding bacterial cells in a polysaccharide-rich matrix that limits antibiotic penetration. Here we dissect the anti-biofilm bovine host-defense cathelicidin peptide fragment bac7 (1-35), exploring its anti-biofilm mechanism, evaluating its ability to curb dissemination of hypervirulent K. pneumoniae, and testing its breadth of activity against diverse clinical isolates. Transcriptomic profiling revealed that bac7(1-35) simultaneously compromises the bacterial membrane and inhibits ribosomal function, a dual assault that precipitates rapid biofilm collapse and blocks bacterial spread. Further, the peptide eradicated biofilms produced by the strongest MDR clinical isolates in the Multidrug-Resistant Organism Repository and Surveillance Network (MRSN) diversity panel. Although bac7 (1-35) kills bacterial cells via a cytosolic mechanism, membrane interaction profiles varied among MRSN isolates, correlating with differential peptide translocation. In a delayed-treatment murine skin-abscess model, bac7 (1-35) halted in vivo dissemination of the hypervirulent strain NTUH-K2044. Collectively, these results delineate a multifaceted mode of action for bac7 (1-35) and underscore its therapeutic promise against biofilm-associated MDR K. pneumoniae infections. Author SummaryKlebsiella pneumoniae is a top-priority pathogen for new therapies, with many strains already approaching pan-drug resistant status. Biofilm formation further complicates treatment, yet biofilm-active therapeutics have not reached the clinic, in part because we still lack a detailed understanding of how to disrupt these impenetrable structures. Antimicrobial peptides are promising candidates and have shown biofilm-disruption potential. Here we provide mechanistic insight into how a host defense peptide dismantles pre-formed K. pneumoniae biofilms. We find that the peptides dual targeting of bacterial membranes and ribosomes triggers dispersal from the biofilm state and concomitantly downregulates factors required for surface attachment and extracellular matrix production. This mechanism involves a protein that, to our knowledge, has not been characterized in K. pneumoniae. Our findings reveal a switch that can be leveraged to reprogram biofilm maintenance toward dispersal in K. pneumoniae, advancing the path to peptide-based antibiofilm therapeutics.

microbiology↗

bioRxiv2025

Control of myogenesis by the E3 ubiquitin ligase CUL3-BTBD9

Metazoan development requires that cells adopt specific identities at the right time and place with-in an embryo. Central to the success of this process are posttranslational modifications that control the activity, stability or localization of crucial transducers of differentiation signals. During muscle development, modification of proteins with ubiquitin is known to play an important role, but the enzymatic machinery of ubiquitylation that drives myogenesis remains incompletely understood. Here, we identify CUL3BTBD9 as an E3 ubiquitin ligase that is essential for myogenesis in vitro. CUL3BTBD9 binds and ubiquitylates CAV1, the central component of caveolae that modulate insulin signaling during muscle formation. CUL3BTBD9 and CAV1 are required for insulin-dependent activation of the AKT kinase in myoblasts, thereby safeguarding the ability of muscle precursors to respond to insulin signals. Together, this work identifies CUL3BTBD9 as a regulator of myogenesis that acts by modulating plasma-membrane localized events critical for cell fate specification.

cell biology↗

bioRxiv2025

The Consortium for Genomic Diversity, Ancestry, and Health in Colombia (CODIGO): building local capacity in genomics, bioinformatics, and precision medicine

The Consortium for Genomic Diversity, Ancestry, and Health in Colombia (CODIGO) aims to build a community of Colombian researchers in support of local capacity in genomics, bioinformatics, and precision health. Here, we present the first CODIGO data release and the consortium web platform, including annotations for more than 95 million genetic variants from 1,441 samples representing 14 populations from across the country. CODIGO samples show a wide range of African (16.7%), European (50.6%), and Indigenous American (32.8%) genetic ancestry components, with five distinct ancestry clusters. Thousands of ancestry-enriched variants, with divergent allele frequencies across clusters, show pharmacogenomic and clinical genetic associations. Examples include African ancestry-enriched variants associated with fast metabolism of the immunosuppressive drug tacrolimus and malaria resistance and European ancestry-enriched variants associated with nicotine dependence and hereditary hemochromatosis. CODIGO reveals the nexus between ancestry and health in Colombia and underscores the utility of collaborative genome sequence analysis efforts.

genomics↗

bioRxiv2022

Cold exposure induces dynamic changes in circulating triacylglycerol species, which is dependent on intracellular lipolysis: a randomized cross-over trial

BackgroundThe application of cold exposure has emerged as an approach to enhance whole-body lipid catabolism. The global effect of cold exposure on the lipidome in humans has been reported with mixed results depending on intensity and duration of cold. MethodsThis secondary study was based on data from a previous randomized cross-over trial (ClinicalTrials.gov ID: NCT03012113). We performed sequential lipidomic profiling in serum during 120 min cold exposure of human volunteers. Next, the intracellular lipolysis was blocked in mice using a small-molecule inhibitor of adipose triglyceride lipase (ATGL; Atglistatin), and were exposed to cold for a similar duration. The quantitative lipidomic profiling was assessed in-depth using the Lipidyzer platform. FindingsCold exposure gradually increased circulating free fatty acids reaching a maximum at 60 min, and transiently decreased total triacylglycerols (TAGs) only at 30 min. A broad range of TAG species was initially decreased, in particular unsaturated and polyunsaturated TAG species with [≤]5 double bonds, while after 120 min a significant increase was observed for polyunsaturated TAG species with [≥]6 double bonds. The mechanistic study in mice revealed that the cold-induced increase in polyunsaturated TAGs was largely prevented by blocking adipose triglyceride lipase. InterpretationWe interpret these findings as that cold exposure feeds thermogenic tissues with TAG-derived fatty acids for combustion, resulting in a decrease of circulating TAG species, followed by increased hepatic production of polyunsaturated TAG species induced by liberation of free fatty acids stemming from adipose tissue. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSCold exposure has emerged as a novel non-pharmacological strategy to enhance whole-body lipid catabolism, to improve lipid homeostasis and ultimately cardiometabolic health. In mice, cold exposure accelerates the clearance of triacylglycerol (TAG)-rich lipoproteins from the circulation, reducing circulating TAGs. In humans however, the effect of cold exposure on whole-body TAG metabolism remained thus far controversial, as mixed results are reported depending on intensity and duration of cold. Added value of this studyHere, we performed sequential lipidomic profiling in serum during 120 min cold exposure of human volunteers. We show that cold exposure gradually increases circulating free fatty acids and transiently decreases total TAGs after 30 min, accompanied with a dynamic change in circulating TAGs as dependent on their saturation status and length. Specifically, cold exposure decreases a broad range of more saturated and shorter TAG species, while after 90-120 min polyunsaturated TAG species with [≥]6 double bonds start to increase. Subsequently, we performed a mechanistic study in mice, in which we show that the cold-induced increase in polyunsaturated TAGs is largely prevented when blocking intracellular lipolysis. Implications of all the available evidenceOur findings describe a mechanism by which cold exposure provides thermogenic tissues with TAG-derived fatty acids for combustion. At the same time, cold exposure increases lipolysis in white fat to drive hepatic TAG production to further feed thermogenic tissues. For the first time, these results show that the TAG lowering effect of cold exposure as observed in mice can be recapitulated in humans, which warrants further studies on the beneficial effects of cold exposure on accelerating lipid metabolism to improve cardiometabolic health.

physiology↗

bioRxiv2021

A distinct CD115- erythro-myeloid precursor present at the maternal-embryonic interface and in the bone marrow of adult mice

During ontogeny, macrophages develop from CD115+ precursors, including erythro-myeloid progenitors (EMP). EMP arise in the embryonic yolk sac, the primary site of early haematopoiesis. In adults, CD115+ bone marrow-derived monocytes represent essential macrophage precursors. Herein, we identify a CD115- macrophage precursor within the adult bone marrow that is unrelated to the classical monocyte lineage but rather shares transcriptomic and functional characteristics of embryonic EMP. These EMPROR (for Erythro Myeloid Precursor) cells are capable of efficiently generating macrophages in disease settings. During early development, EMPROR cells were largely absent from the yolk sac but were instead found at the embryonic-maternal interface in the uterine wall. Unexpectedly, the latter site contains robust haematopoietic activity and harbours defined embryonic haematopoietic progenitor cells, including classical CD115+ EMP. Our data suggest the existence of an alternative pathway of macrophage generation in the adult. Further, we uncover a hitherto unknown site of earliest blood cell development.

immunology↗