Systems Biology
Chronic Wound Initiation: Single-Cell RNAseq of Cutaneous Wound Tissue and Contributions of Oxidative Stress to Initiation of Chronicity
Antioxidants (Basel). 2025 Feb 13;14(2):214. doi: 10.3390/antiox14020214.
ABSTRACT
Chronic wounds (CWs) in humans affect millions of people in the US alone, cost billions of dollars, cause much suffering, and still there are no effective treatments. Patients seek medical care when wound chronicity is already established, making it impossible to investigate factors that initiate chronicity. In this study, we used a diabetic mouse model of CWs that mimics many aspects of chronicity in humans. We performed scRNAseq to compare the cell composition and function during the first 72 h post-injury and profiled 102,737 cells into clusters of all major cell types involved in healing. We found two types of fibroblasts. Fib 1 (pro-healing) was enriched in non-CWs (NCWs) whereas Fib 2 (non-healing) was in CWs. Both showed disrupted proliferation and migration, and extracellular matrix (ECM) deposition in CWs. We identified several subtypes of keratinocytes, all of which were more abundant in NCWs, except for Channel-related keratinocytes, and showed altered migration, apoptosis, and response to oxidative stress (OS) in CWs. Vascular and lymphatic endothelial cells were both less abundant in CWs and both had impaired migration affecting the development of endothelial and lymphatic microvessels. Study of immune cells showed that neutrophils and mast cells are less abundant in CWs and that NCWs contained more proinflammatory macrophages (M1) whereas CWs were enriched in anti-inflammatory macrophages (M2). Also, several genes involved in mitochondrial function were abnormally expressed in CWs, suggesting impaired mitochondrial function and/or higher OS. Heat shock proteins needed for response to OS were downregulated in CWs, potentially leading to higher cellular damage. In conclusion, the initiation of chronicity is multifactorial and involves various cell types and cellular functions, indicating that one type of treatment will not fix all problems, unless the root cause is fundamental to the cell and molecular mechanisms of healing. We propose that such a fundamental process is high OS and its association with wound infection/biofilm.
PMID:40002400 | DOI:10.3390/antiox14020214
Oxidative Score and Microvesicle Profile Suggest Cardiovascular Risk in Chronic Kidney Disease
Antioxidants (Basel). 2025 Feb 3;14(2):178. doi: 10.3390/antiox14020178.
ABSTRACT
Chronic kidney disease (CKD) is associated with a high incidence of cardiovascular disease (CVD) due to the accumulation of uremic toxins, altered redox state, and chronic systemic inflammation. This study aimed to analyze the relationship between the redox status of patients with CKD and the phenotype of microvesicles (MVs) subtypes, and cardiovascular events. The oxidative stress level of each participant was determined using an individualized OXY-SCORE. The relationship between pro-oxidant and antioxidant parameters and the expression of membrane markers in endothelial-derived microvesicles (EMVs) and platelet-derived microvesicles (PMVs) was established. Patients with advanced CKD (ACKD) and hemodialysis (HD) had a higher OXY-SCORE than healthy subjects (HS), whereas peritoneal dialysis (PD) patients had similar scores to HS. PD patients showed elevated PMVs and CD41 expression, whereas HD patients had higher EMVs and CD31 expression. Patients with ACKD had higher tissue factor (TF) expression in the PMVs and EMVs. TF expression was correlated with xanthine oxidase (XO) activity and was negatively correlated with antioxidant parameters. Patients with cardiovascular events show elevated TF. In conclusion, microvesicles and oxidative stress may serve as markers of cardiovascular risk in CKD, with TF expression in PMVs and EMVs being potential predictive and prognostic biomarkers of CVD.
PMID:40002365 | DOI:10.3390/antiox14020178
Biosynthesis of Edible Terpenoids: Hosts and Applications
Foods. 2025 Feb 17;14(4):673. doi: 10.3390/foods14040673.
ABSTRACT
Microbial foods include microbial biomass, naturally fermented foods, and heterologously synthesized food ingredients derived from microbial fermentation. Terpenoids, using isoprene as the basic structure, possess various skeletons and functional groups. They exhibit diverse physicochemical properties and physiological activities, such as unique flavor, anti-bacterial, anti-oxidant, anti-cancer, and hypolipemic, making them extensively used in the food industry, such as flavor, fragrance, preservatives, dietary supplements, and medicinal health food. Compared to traditional strategies like direct extraction from natural species and chemical synthesis, microbial cell factories for edible terpenoids have higher titers and yields. They can utilize low-cost raw materials and are easily scaling-up, representing a novel green and sustainable production mode. In this review, we briefly introduce the synthetic pathway of terpenoids and the applications of microbial cell factories producing edible terpenoids. Secondly, we highlight several typical and non-typical microbial chassis in edible terpenoid-producing cell factories. In addition, we reviewed the recent advances of representative terpenoid microbial cell factories with a gram-scale titer in food flavor, food preservation, nutritional enhancers, and medicinal health foods. Finally, we predict the future directions of microbial cell factories for edible terpenoids and their commercialization process.
PMID:40002116 | DOI:10.3390/foods14040673
The Curse of the Red Pearl: A Fibroblast-Specific Pearl-Necklace Mitochondrial Phenotype Caused by Phototoxicity
Biomolecules. 2025 Feb 19;15(2):304. doi: 10.3390/biom15020304.
ABSTRACT
The dynamic nature of mitochondria makes live cell imaging an important tool in mitochondrial research. Although imaging using fluorescent probes is the golden standard in studying mitochondrial morphology, these probes might introduce aspecific features. In this study, live cell fluorescent imaging was applied to investigate a pearl-necklace-shaped mitochondrial phenotype that arises when mitochondrial fission is restricted. In this fibroblast-specific pearl-necklace phenotype, constricted and expanded mitochondrial regions alternate. Imaging studies revealed that the formation time of this pearl-necklace phenotype differs between laser scanning confocal, widefield and spinning disk confocal microscopy. We found that the phenotype formation correlates with the excitation of the fluorescent probe and is the result of phototoxicity. Interestingly, the phenotype only arises in cells stained with red mitochondrial dyes. Serial section electron tomography of the pearl-necklace mitochondria revealed that the mitochondrial membranes remained intact, while the cristae structure was altered. Furthermore, filaments and ER were present at the constricted sites. This study illustrates the importance of considering experimental conditions for live cell imaging to prevent imaging artifacts that can have a major impact on the obtained results.
PMID:40001607 | DOI:10.3390/biom15020304
The Matrix of Mitochondrial Imaging: Exploring Spatial Dimensions
Biomolecules. 2025 Feb 5;15(2):229. doi: 10.3390/biom15020229.
ABSTRACT
Mitochondria play a crucial role in human biology, affecting cellular processes at the smallest spatial scale as well as those involved in the functionality of the whole system. Imaging is the most important research tool for studying the fundamental role of mitochondria across these diverse spatial scales. A wide array of available imaging techniques have enabled us to visualize mitochondrial structure and behavior, as well as their effect on cells and tissues in a range from micrometers to centimeters. Each of the various imaging techniques that are available offers unique advantages tailored to specific research needs. Selecting an appropriate technique suitable for the scale and application of interest is therefore crucial, but can be challenging due to the large range of possibilities. The aim of this review is two-fold. First, we provide an overview of the available imaging techniques and discuss their strengths and limitations for applications across the sub-mitochondrial, cellular, tissue and organ levels for the imaging of mitochondria. Second, we identify opportunities for novel applications and advancement in the field. We emphasize the importance of integration across scales in mitochondrial imaging studies, particularly to bridge the gap between microscopic and non-invasive techniques. While integrating these diverse scales is challenging, primarily because such multi-scale approaches require expertise that spans different imaging modalities, we argue that integration has the potential to provide groundbreaking insights into mitochondrial biology. By providing a comprehensive overview of imaging techniques, this review paves the way for multi-scale imaging initiatives in mitochondrial research.
PMID:40001532 | DOI:10.3390/biom15020229
Structural Characterization of the Dimers and Selective Synthesis of the Cyclic Analogues of the Antimicrobial Peptide Cm-p5
Antibiotics (Basel). 2025 Feb 13;14(2):194. doi: 10.3390/antibiotics14020194.
ABSTRACT
Background/Objectives: Cm-p5 and its cyclic monomeric and dimeric analogues are known for their antifungal, antibacterial, antiviral, and antibiofilm activities. Previously, our cyclization method produced a mixture of peptides that were difficult to separate, which was then improved by a selective synthesis of the parallel dimer and its differentiation from the antiparallel by comparison of the retention times in RP-HPLC. Methods: Here, we developed a more reliable identification method for the Cm-p5 dimer identification, which included chymotrypsin proteolytic digestion and sequencing of the different fragments by ESI-MSMS. We also improved our cyclization methods to specifically produce higher amounts of the desired cyclic variant, either cyclic monomer or dimer. Results: We show that liquid phase oxidation with 20% DMSO or iodine oxidation yields only the cyclic analogue. However, the on-resin oxidation with iodine showed greater efficacy and efficiency. Additionally, liquid phase cyclization yields the antiparallel dimer in high EtOH or peptide concentration, indicating a kinetic control. On the other hand, the parallel dimer was preferentially produced in 5% of TFE and low peptide concentration without the formation of the cyclic analogue indicating a thermodynamic control. Conclusions: In conclusion, we report that chymotryptic digestion combined with ESI-MS and MS/MS allows an unambiguous differentiation of Cm-p5 dimers. Here, we develop more selective and efficient methods for the synthesis of cyclic and dimeric analogues of Cm-p5.
PMID:40001437 | DOI:10.3390/antibiotics14020194
Phage Therapy for Orthopaedic Infections: The First Three Cases from the United Kingdom
Antibiotics (Basel). 2025 Jan 22;14(2):114. doi: 10.3390/antibiotics14020114.
ABSTRACT
Background: Bacteriophages (phages) are viruses that infect and kill bacteria. The antimicrobial resistance crisis has driven renewed interest in phage therapy, including the use of phages to treat chronic orthopaedic infections. Methods: Here, we present the results of the first three orthopaedic patients treated with phage therapy in the United Kingdom. Results: The first patient was treated in May 2023 and received phages active against Staphylococcus aureus. At nine months follow-up, the patient's wound remained healed, the C-reactive protein normal and the patient was walking independently. The second patient received phages active against Klebsiella pneumoniae and S. aureus; the infection remained unresolved. The third patient received phages active against Staphylococcus epidermidis; at six months follow-up, the patient was free of infection. Endotoxin was considered at least partially responsible for mild self-limiting adverse effects in two cases. Conclusions: These promising results hint at the potential for phage therapy to transform the care of chronic orthopaedic infections.
PMID:40001358 | DOI:10.3390/antibiotics14020114
Causal effects of education, intelligence, and income on COVID-19: evidence from a Mendelian randomization study
Hum Genomics. 2025 Feb 25;19(1):18. doi: 10.1186/s40246-025-00731-y.
ABSTRACT
BACKGROUND: The protective effects of higher educational attainment (EA) and intelligence on COVID-19 outcomes are not yet understood with regard to their dependency on income. The objective of our study was to examine the overall as well as independent effects of the three psychosocial factors on the susceptibility to and severity of COVID-19. To accomplish this, we utilized genetic correlation, Mendelian randomization (MR), and multivariable MR (MVMR) analyses to evaluate genetic associations between EA, intelligence, household income, and three specific COVID-19 outcomes: SARS-CoV-2 infection, hospitalized COVID-19, and critical COVID-19.
RESULTS: The genetic correlation analysis revealed that COVID-19 outcomes were negatively correlated with the three psychosocial factors (rg: -0.19‒-0.36). The MR analysis indicated that genetic liability to EA, intelligence, and income exerted overall protective effects against SARS-CoV-2 infection (OR: 0.86‒0.92), hospitalized COVID-19 (OR: 0.70‒0.80), and critical COVID-19 (OR: 0.65‒0.85). MVMR analysis revealed that elevated levels of EA conferred independent protective effects against SARS-CoV-2 infection (OR: 0.85), hospitalization due to COVID-19 (OR: 0.79), and critical COVID-19 (OR: 0.63). Furthermore, intelligence exhibited a negative association with the risk of SARS-CoV-2 infection (OR: 0.91), whereas a higher income was linked to an elevated risk of SARS-CoV-2 infection (OR: 1.13).
CONCLUSIONS: Our findings indicated that EA could significantly reduce the risk and severity of COVID-19, regardless of intelligence and income. However, the impact of intelligence or income on COVID-19 severity was not supported by our research.
PMID:40001252 | DOI:10.1186/s40246-025-00731-y
Th1-poised naive CD4 T cell subpopulation reflects anti-tumor immunity and autoimmune disease
Nat Commun. 2025 Feb 25;16(1):1962. doi: 10.1038/s41467-025-57237-3.
ABSTRACT
Naïve CD4 T cells are traditionally viewed as a quiescent, homogeneous, resting population, but emerging evidence reveals their heterogeneity, which can be crucial for understanding disease contexts and therapeutic outcomes. In this study, we identify distinct subpopulations within both murine and human naïve CD4 T cells by single cell-RNA-sequencing (scRNA-seq), particularly focusing on a subpopulation that expresses super-high levels of interleukin-7 receptor (IL-7Rsup-hi), along with CD97, IL-18R, and Ly6C. This subpopulation, absent in the thymus and peripherally induced, exhibits type 1 helper T cell (Th1)-poised characteristics and contributes to the inhibition of cancer progression in B16F10 tumor-bearing mice. In humans, this IL-7Rsup-hi subpopulation expressing CD97 correlates with the responsiveness to anti-PD-1 therapy in cancer patients and the disease state of multiple sclerosis. By elucidating the heterogeneity of naive CD4 T cells and identifying a Th1-poised subpopulation capable of robust type 1 responses, we highlight the importance of this heterogeneity in inflammatory conditions for defining the disease states and predicting drug responsiveness.
PMID:40000667 | DOI:10.1038/s41467-025-57237-3
The Great Reset: A "Tuft" Journey Towards Tumorigenesis
Cell Mol Gastroenterol Hepatol. 2025 Feb 22:101476. doi: 10.1016/j.jcmgh.2025.101476. Online ahead of print.
NO ABSTRACT
PMID:39999952 | DOI:10.1016/j.jcmgh.2025.101476
Biomolecular condensates at the plasma membrane: Insights into plant cell signaling
Curr Opin Plant Biol. 2025 Feb 24;84:102697. doi: 10.1016/j.pbi.2025.102697. Online ahead of print.
ABSTRACT
Biomolecular condensates, often formed through liquid-liquid phase separation (LLPS), are increasingly recognized as a critical mechanism for cellular compartmentalization across diverse biological systems. Although traditionally considered membrane-less entities, recent discoveries highlight their dynamic interactions with membranes, where they regulate various processes, including signal transduction. Signaling lipids are observed in condensates. Despite these advancements, our understanding of such condensates in plant biology remains limited. This review highlights recent studies involving membrane-associated condensates in plants, focusing particularly on their interactions with the plasma membrane (PM) and their potential roles in PM-based signaling.
PMID:39999604 | DOI:10.1016/j.pbi.2025.102697
MInfer: Bridging MetaboAnalyst and Jacobian analysis for metabolomic networks
Comput Methods Programs Biomed. 2025 Feb 18;263:108672. doi: 10.1016/j.cmpb.2025.108672. Online ahead of print.
ABSTRACT
BACKGROUND AND OBJECTIVE: Metabolomic interaction networks provide critical insights into the dynamic relationships between metabolites and their regulatory mechanisms. This study introduces MInfer, a novel computational framework that integrates outputs from MetaboAnalyst, a widely used metabolomic analysis tool, with Jacobian analysis to enhance the derivation and interpretation of these networks.
METHODS: MInfer combines the comprehensive data processing capabilities of MetaboAnalyst with the mathematical modeling power of Jacobian analysis. This framework was applied to various metabolomic datasets, employing advanced statistical tests to construct interaction networks and identify key metabolic pathways.
RESULTS: The application of MInfer revealed significant metabolic pathways and potential regulatory mechanisms across multiple datasets. The framework demonstrated high precision, sensitivity, and specificity in identifying interactions, enabling robust network interpretations.
CONCLUSIONS: MInfer enhances the interpretation of metabolomic data by providing detailed interaction networks and uncovering key regulatory insights. This tool holds significant potential for advancing the study of complex biological systems.
PMID:39999596 | DOI:10.1016/j.cmpb.2025.108672
Assessment of liver injury potential of investigational medicines in drug development
Hepatology. 2025 Feb 25. doi: 10.1097/HEP.0000000000001281. Online ahead of print.
ABSTRACT
Drug-induced liver injury (DILI) is rare in clinical practice but when it occurs it can lead to acute liver failure and death. Drug developers and regulators undertake a series of steps to identify the DILI potential of a medication before it is approved for marketing. Preclinical testing by drug developers typically involves a multitude of in vitro assays and in vivo animal experiments before a compound is moved into first-in-human phase 1 testing. Over the last two decades, there have been a number of advances in preclinical screening for DILI potential of a new chemical entity, but these approaches tend to be overly sensitive with insufficient positive predictive value. Once in clinical trials, the DILI potential of an investigational agent and risks to a participant are carefully managed through patient selection, DILI monitoring paradigms, and drug interruption and discontinuation criteria, in close concert with the regulators. Recent developments in Quantitative Systems Toxicology offer promising and complementary in silico approaches to predict the compound's risk for DILI via multifaceted systems biology. When a drug developer submits a New Drug Application (NDA) for marketing approval, regulators review the preclinical and clinical trial data in a structured fashion to assess the DILI risk. While these approaches have been successful in dramatically reducing the marketing approval of medications eventually associated with hepatotoxicity, many challenges remain in identifying the risk for DILI during preclinical and early-to-late clinical development stages for genetic medicines, biological agents, and immunotherapies. In this review, we discuss current preclinical, in-silico, and clinical development approaches to screen for DILI potential of an investigational agent and provide a high-level description of regulators' approach for assessing DILI risk in an NDA.
PMID:39999469 | DOI:10.1097/HEP.0000000000001281
The RNA-binding protein RBPMS inhibits smooth muscle cell-driven vascular remodeling in atherosclerosis and vascular injury
Proc Natl Acad Sci U S A. 2025 Mar 4;122(9):e2415933122. doi: 10.1073/pnas.2415933122. Epub 2025 Feb 25.
ABSTRACT
Atherosclerosis and vessel wall trauma induce vascular smooth muscle cell (VSMC) phenotypic modulation, leading to plaque cap growth and postintervention restenosis. Our systems biology approach identified RNA binding protein, mRNA processing factor (RBPMS) as a conserved, VSMC-specific gene associated with VSMC modulation in atherosclerosis. RBPMS gene expression positively correlates with VSMC contractile markers in human and murine atherosclerotic arteries as well as in two vascular injury models during the postinjury intimal hyperplasia phase. RBPMS promotes contractile VSMC differentiation, reduces plaque cap development in high-fat diet-fed apolipoprotein E-null (ApoE-/-) murine atherosclerotic arteries, and inhibits intimal hyperplasia. Mechanistically, the RBPMS protein interacts with the myocardin (MYOCD) pre-mRNA and enhances MYOCD_v3/MYOCD_v1 transcript balance through alternative exon 2a splicing. RBPMS promotes the VSMC contractile phenotype and reduces their fibroproliferative activity in a MYOCD_v3a-dependent manner. RBPMS enhances Myocd_v3/Myocd_v1 transcript balance in both atherosclerotic and injured vessels. RBPMS may inhibit VSMC-driven plaque cap development and intervention-induced restenosis.
PMID:39999164 | DOI:10.1073/pnas.2415933122
Synthesis of Autotaxin-Inhibiting Lipid Nanoparticles to Regulate Autophagy and Inflammatory Responses in Activated Macrophages
Tissue Eng Regen Med. 2025 Feb 25. doi: 10.1007/s13770-025-00705-0. Online ahead of print.
ABSTRACT
BACKGROUND: Autotaxin (ATX), an ENPP2 enzyme, regulates lipid signaling by converting lysophosphatidylcholine to lysophosphatidic acid (LPA). Dysregulation of the ATX/LPA axis promotes inflammation and disease progression. BMP-22, a lipid ATX inhibitor, effectively reduces LPA production. However, its clinical utility is hampered by limitations in solubility and pharmacokinetics. To overcome these limitations, we developed BMP-22-incorporated lipid nanoparticles (LNP-BMP) to improve utility while maintaining ATX inhibition efficacy.
METHODS: LNP-BMP was synthesized by incorporating DOTAP, DOPE, cholesterol, 18:0 PEG2000-PE, and together with BMP-22. The formulation of LNP-BMP was optimized and characterized by testing different molar ratios of BMP-22. The autophagy recovery and anti-inflammatory effects of LNP-BMP via ATX inhibition were evaluated in both macrophage cell line and mouse-derived primary macrophages.
RESULTS: LNP-BMP was shown to retain its functionality as an ATX inhibitor and maintain the physical characteristics upon BMP-22 integration. Synthesized LNP-BMP exerted superior ability to inhibit ATX activity. When applied to M1-induced macrophages, LNP-BMP exhibited substantial anti-inflammatory effects and successfully restored autophagy activity.
CONCLUSION: The results demonstrate that LNP-BMP effectively inhibits ATX, achieving both anti-inflammatory effects and autophagy restoration, highlighting its potential as a standalone immunotherapeutic agent. Furthermore, the capacity to load therapeutic drugs into this formulation offers promising opportunities for further therapeutic strategies.
PMID:39998744 | DOI:10.1007/s13770-025-00705-0
A large language model framework for literature-based disease-gene association prediction
Brief Bioinform. 2024 Nov 22;26(1):bbaf070. doi: 10.1093/bib/bbaf070.
ABSTRACT
With the exponential growth of biomedical literature, leveraging Large Language Models (LLMs) for automated medical knowledge understanding has become increasingly critical for advancing precision medicine. However, current approaches face significant challenges in reliability, verifiability, and scalability when extracting complex biological relationships from scientific literature using LLMs. To overcome the obstacles of LLM development in biomedical literature understating, we propose LORE, a novel unsupervised two-stage reading methodology with LLM that models literature as a knowledge graph of verifiable factual statements and, in turn, as semantic embeddings in Euclidean space. LORE captured essential gene pathogenicity information when applied to PubMed abstracts for large-scale understanding of disease-gene relationships. We demonstrated that modeling a latent pathogenic flow in the semantic embedding with supervision from the ClinVar database led to a 90% mean average precision in identifying relevant genes across 2097 diseases. This work provides a scalable and reproducible approach for leveraging LLMs in biomedical literature analysis, offering new opportunities for researchers to identify therapeutic targets efficiently.
PMID:39998433 | DOI:10.1093/bib/bbaf070
SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx
mBio. 2025 Feb 25:e0401524. doi: 10.1128/mbio.04015-24. Online ahead of print.
ABSTRACT
The gastrointestinal (GI) tract is a site of replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and GI symptoms are often reported by patients. SARS-CoV-2 cell entry depends upon heparan sulfate (HS) proteoglycans, which commensal bacteria that bathe the human mucosa are known to modify. To explore human gut HS-modifying bacterial abundances and how their presence may impact SARS-CoV-2 infection, we developed a task-based analysis of proteoglycan degradation on large-scale shotgun metagenomic data. We observed that gut bacteria with high predicted catabolic capacity for HS differ by age and sex, factors associated with coronavirus disease 2019 (COVID-19) severity, and directly by disease severity during/after infection, but do not vary between subjects with COVID-19 comorbidities or by diet. Gut commensal bacterial HS-modifying enzymes reduce spike protein binding and infection of authentic SARS-CoV-2, suggesting that bacterial grooming of the GI mucosa may impact viral susceptibility.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019, can infect the gastrointestinal (GI) tract, and individuals who exhibit GI symptoms often have more severe disease. The GI tract's glycocalyx, a component of the mucosa covering the large intestine, plays a key role in viral entry by binding SARS-CoV-2's spike protein via heparan sulfate (HS). Here, using metabolic task analysis of multiple large microbiome sequencing data sets of the human gut microbiome, we identify a key commensal human intestinal bacteria capable of grooming glycocalyx HS and modulating SARS-CoV-2 infectivity in vitro. Moreover, we engineered the common probiotic Escherichia coli Nissle 1917 (EcN) to effectively block SARS-CoV-2 binding and infection of human cell cultures. Understanding these microbial interactions could lead to better risk assessments and novel therapies targeting viral entry mechanisms.
PMID:39998226 | DOI:10.1128/mbio.04015-24
<em>Campylobacter jejuni</em> resistance to human milk involves the acyl carrier protein AcpP
mBio. 2025 Feb 25:e0399724. doi: 10.1128/mbio.03997-24. Online ahead of print.
ABSTRACT
Campylobacter jejuni is a common foodborne pathogen worldwide that is associated with high rates of morbidity and mortality among infants in low- to middle-income countries (LMICs). Human milk provides infants with an important source of nutrients and contains antimicrobial components for protection against infection. However, recent studies, including our own, have found significantly higher levels of Campylobacter in diarrheal stool samples collected from breastfed infants compared to non-breastfed infants in LMICs. We hypothesized that C. jejuni has unique strategies to resist the antimicrobial properties of human milk. Transcriptional profiling found human milk exposure induces genes associated with ribosomal function, iron acquisition, and amino acid utilization in C. jejuni strains 81-176 and 11168. However, unidentified proteinaceous components of human milk prevent bacterial growth. Evolving both C. jejuni isolates to survive in human milk resulted in mutations in genes encoding the acyl carrier protein (AcpP) and the major outer membrane porin (PorA). Introduction of the PorA/AcpP amino acid changes into the parental backgrounds followed by electron microscopy showed distinct membrane architectures, and the AcpP changes not only significantly improved growth in human milk, but also yielded cells surrounded with outer membrane vesicles. Analyses of the phospholipid and lipooligosaccharide (LOS) compositions suggest an imbalance in acyl chain distributions. For strain 11168, these changes protect both evolved and 11168∆acpPG33R strains from bacteriophage infection and polymyxin killing. Taken together, this study provides insights into how C. jejuni may evolve to resist the bactericidal activity of human milk and flourish in the hostile environment of the gastrointestinal tract.
IMPORTANCE: In this study, we evolved C. jejuni strains which can grow in the presence of human milk and found that cell membrane alterations may be involved in resistance to the antimicrobial properties of human milk. These bacterial membrane changes are predominantly linked to amino acid substitutions within the acyl carrier protein, AcpP, although other bacterial components, including PorA, are likely involved. This study provides some insights into possible strategies for C. jejuni survival and propagation in the gastrointestinal tract of breastfed infants.
PMID:39998218 | DOI:10.1128/mbio.03997-24
Refining the genome of alkylbenzene-degrading <em>Rhodococcus</em> sp. DK17 and comparative analysis with genomes of its deletion mutants
Microbiol Resour Announc. 2025 Feb 25:e0113424. doi: 10.1128/mra.01134-24. Online ahead of print.
ABSTRACT
Rhodococcus sp. strain DK17 degrades various alkylbenzenes, including o-xylene, making it a potential biocatalyst for the production of fine chemicals. DK17 carries the degradative genes on linear mega-plasmids. Here, we present the refined DK17 genome and analyze the genetic variations in UV-induced mutants DK176 and DK180.
PMID:39998182 | DOI:10.1128/mra.01134-24
Technical, Tactical, and Time-Motion Match Profiles of the Forwards, Midfielders, and Defenders of a Men's Football Serie A Team
Sports (Basel). 2025 Jan 21;13(2):28. doi: 10.3390/sports13020028.
ABSTRACT
The present study aimed to verify the (1) differences between players' roles in relation to technical and tactical and time-motion indicators, and the (2) relationships between individual time-motion and technical and tactical indicators for each role in a men's Italian football Serie A team. A total of 227 performances were analyzed (28 players: 8 forwards, FWs; 11 midfielders, MDs; 9 defenders, DFs). Technical and tactical indicators, such as ball possession (played balls, successful passes, successful playing patterns, lost balls, ball possession time), offensive play (total and successful dribbles, crosses, assists), and shooting (total shots, shots on target) were obtained by means of Panini Digital (DigitalSoccer Project S.r.l). In addition, a time-motion analysis included the total distance, distances covered at intensities of 16.0-19.8 km/h, 19.8-25.2 km/h, and over 25.2 km/h, the average recovery time between metabolic power peaks, and burst occurrence, the latter of which was performed by means of a 18 Hz GPS device (GPexe Pro2 system tool) worn by the players. Results showed role-specific differences: MDs covered more distance, while DFs had better ball possession. MDs and DFs had more successful playing patterns, and MDs and FWs performed more dribbles and shots. Strong correlations (p < 0.01, ρ > 0.8) were found between bursts and assists for FWs, high-intensity running and ball possession for MDs, and distance, dribbling, and shots for DFs. These findings highlight the importance of individual and tailored training programs to optimize role-specific performance demands.
PMID:39997959 | DOI:10.3390/sports13020028