SEARCH · PubMed Health

Results for “Whole genome sequencing analysis”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2025

Whole genome sequence analysis of low-density lipoprotein cholesterol across 246 K individuals.

BACKGROUND: Rare genetic variation provided by whole genome sequence datasets has been relatively less explored for its contributions to human traits. Meta-analysis of sequencing data offers advantages by integrating larger sample sizes from diverse cohorts, thereby increasing the likelihood of discovering novel insights into complex traits. Furthermore, emerging methods in genome-wide rare variant association testing further improve power and interpretability. RESULTS: Here, we conduct the largest meta-analysis of whole genome sequencing for low-density lipoprotein cholesterol (LDL-C), a therapeutic target for coronary artery disease, analyzing data from 246 K participants and integrating 1.23B variants from the UK Biobank and the Trans-Omics for Precision Medicine (TOPMed) program. We identify numerous rare coding and non-coding gene associations related to LDL-C, with replication across 86 K participants in All of Us. Our findings are based on single-variant analyses, rare coding and non-coding variant aggregation tests, and sliding window approaches. Through this comprehensive analysis, we identify 704 novel single-variant associations, 25 novel rare coding variant aggregates, 28 novel rare non-coding variant aggregates, and one novel sliding window aggregate. CONCLUSIONS: This study provides a meta-analysis framework for large-scale whole genome sequence association analyses from diverse population groups, yielding novel rare non-coding variant associations.

Humans↗

PubMed2026

The impact of the COVID-19 pandemic on the incidence of invasive pneumococcal disease in the Czech Republic and whole genome sequencing analysis of Streptococcus pneumoniae serotypes 3 and 19A from 2018-2024.

AIM: To describe in detail changes in the incidence of invasive pneumococcal disease in the Czech Republic during and after the COVID-19 pandemic. Another objective is molecular analysis of S. pneumoniae isolates of serotypes 3 and 19A recovered in the Czech Republic between 2018 and 2024. MATERIAL AND METHODS: Data on the incidence of invasive pneumococcal disease and S. pneumoniae serotypes were obtained from the invasive pneumococcal disease surveillance program in the Czech Republic. S. pneumoniae isolates of serotypes 3 (63) and 19A (66) from 2018-2024 were subjected to whole genome sequencing (WGS) to characterize the GPSCs (Global Pneumococcal Sequence Clusters) and STs (sequence types) and place them in a global context. RESULTS: Results: During the COVID-19 pandemic, a significant decline was observed in the incidence of invasive pneumococcal disease in the Czech Republic. Following the pandemic, the incidence of invasive pneumococcal disease rose again to significantly higher levels than before the pandemic. Compared to the 2018–2019 period, the incidence of certain serotypes increased in 2023–2024, including vaccine serotypes 3, 4, 14, and 15B, while the incidence of serotypes 8, 12F, and 15A, among others, decreased. Whole genome sequencing analysis demonstrated the dominance of GPSC12 ST-180 among serotype 3 isolates throughout the study period. Among serotype 19A isolates, GPSC4 prevailed, particularly ST-416. CONCLUSIONS: The COVID-19 pandemic has demonstrated how rapidly the epidemiological situation of invasive pneumococcal disease can change and that continuous, systematic surveillance of invasive pneumococcal disease is necessary. The best prevention against invasive pneumococcal disease is vaccination, primarily with higher valency pneumococcal conjugate vaccines.

Czech Republic↗

PubMed2025

Evaluating 12 automated, whole-genome sequencing analysis pipelines for Mycobacterium tuberculosis complex: a comparative study.

BACKGROUND: Reliance on complex, custom-built bioinformatics pipelines is a barrier to the implementation of whole-genome sequencing (WGS) of Mycobacterium tuberculosis in high-burden settings in some low-income and middle-income countries (LMICs). Automated analysis pipelines could address this inequity in access to WGS-based diagnostics and surveillance. This study aimed to systematically evaluate the performance and usability of publicly available WGS pipelines for M tuberculosis. METHODS: We identified automated M tuberculosis WGS analysis pipelines through searches of PubMed and GitHub from database inception up to Aug 31, 2024. Accuracy, cost, accessibility, and scalability were assessed for each pipeline. We evaluated the accuracy of genotypic drug susceptibility testing (gDST) using publicly available sequences with phenotypic susceptibility data for 12 antituberculosis drugs. We estimated pooled sensitivity and specificity for each pipeline, across all drugs, by conducting a bivariate meta-analysis, with random effects representing between-drug variability. Lineage classifications were compared, and a previously epidemiologically well-characterised dataset was used to compare measures of genomic relatedness. FINDINGS: Among 28 candidate pipelines, 16 were excluded as they were unmaintained and inexecutable. 12 pipelines (11 compatible with Illumina and four compatible with Nanopore), all free to use, were included for evaluation. Six pipelines processed and stored data remotely, but for five of these six, scalability was limited by the need to upload sequences through web portals. For local processing pipelines, scalability was dependent on substantial local computational resources, data storage capacity, and command-line interfaces that limited user-friendliness. Only one of six remote-processing pipelines removed human DNA sequences before server upload. gDST was similarly accurate across ten of 11 Illumina-compatible pipelines and three of four Nanopore-compatible pipelines. All pipelines classified the main lineages consistently, although there were differences at sublineage resolution. Outputs from three of four pipelines reporting genomic relatedness were compatible with commonly cited single nucleotide polymorphism difference thresholds. INTERPRETATION: Numerous automated analysis pipelines capable of enhancing equity in M tuberculosis WGS are available. Given the overall similarities between the pipelines evaluated in this study in terms of gDST performance, lineage classification, and genomic relatedness inference, non-functional attributes such as availability, accessibility, scalability, and privacy could represent the point of difference for prospective users in LMICs with a high burden of tuberculosis. FUNDING: The Rhodes Trust, Wellcome, Ellison Institute of Technology, and the UK National Institute for Health and Care Research Oxford Biomedical Research Centre.

Mycobacterium tuberculosis↗

PubMed2025

Whole-genome Sequence Analysis Revealed Novel Subjective Cognitive Decline-associated Genes in 10,763 Chinese.

Subjective cognitive decline (SCD) is widely regarded as a potential preclinical stage of Alzheimer's disease (AD), yet its genetic basis remains poorly understood. To address this gap, we investigated genetic biomarkers associated with SCD using whole-genome sequencing (WGS) in 10,763 Chinese participants from the Healthy Zhejiang One Million People Cohort (HOPE Cohort). The discovery stage included 9284 samples, with 1479 samples used for validation. Using a two-stage design, we systematically investigated both common and rare variants associated with SCD. In rare variant analyses, we identified and replicated an association between the upstream region of SEPHS2 and SCD. SEPHS2 is involved in selenophosphate synthesis, and a Mendelian randomization analysis reveals that its expression levels in both blood and brain cerebellum are associated with AD. Additionally, we identified CLVS2, which encodes a protein primarily expressed in neuronal cells, as a potential regulator for SCD based on missense rare variants. Multi-omics evidence suggests that both SEPHS2 and CLVS2 may play roles in neurodegenerative diseases. For common variants, we validated 8 known loci related to cognitive decline, 3 of which originated from the only existing SCD genetic study conducted under a migraine background. Overall, our WGS-based study fills the gap in SCD research by providing vital genetic evidence from an East Asian population and offers insights into the pathogenic mechanisms of SCD.

Aged↗

PubMed2025

Whole genome sequencing analysis of Candida glabrata isolates collected from patients with selected drug-resistant candidiasis hospitalized in Eastern Poland.

The epidemiology data for candidiasis indicate an increase in Candida glabrata infections. Moreover, several reports have shown an increasing number of drug-resistant cases of these infections. The source of drug resistance can often be traced to genetic mutations in genes related to a drug's mechanism of action. Therefore, we conducted whole genome sequencing of several drug-resistant isolates of Candida glabrata collected from patients hospitalized in Eastern Poland to assess whether mutations in selected genes correlated with susceptibility analysis results. The fungal species from patient samples were identified, and the isolated Candida glabrata were subjected to antifungal drug susceptibility testing. The results were interpreted according to the EUCAST and CLSI recommendations. Susceptibility to 5-flucytosine was assessed using the ATB FUNGUS kit. Libraries were prepared according to the NEXTERA XT DNA Library Prep and subsequently sequenced. The outcomes indicated common resistance to two of the three analyzed echinocandins, as well as two cases of simultaneous resistance to echinocandins and selected azole-based drugs. We detected several previously reported mutations in selected resistance-related genes, as well as five that are first described here: ERG5 (M267I), ERG6 (R57K), PDH1 (K438Q, V434I, F600V, V1192S), FCY1 (M129T), and FCY2 (I384F). Neither of the identified nonsynonymous mutations was correlated with the drug resistance demonstrated in the susceptibility testing. Furthermore, we can exclude the possibility of acquired drug resistance, thereby raising questions about the possibility of unknown mechanisms of resistance to azole-based and echinocandin drugs.

Candida glabrata↗

PubMed2026

Whole genome sequencing analysis and functional characterization of Lacticaseibacillus rhamnosus HP-B1083.

Lacticaseibacillus rhamnosus is an important strain for the biotransformation of natural products, and its crude extract exhibits biotransformation effect on glycosidic compounds such as baicalin. To further explore the potential of this strain, particularly given its previously demonstrated high-efficiency β-glucuronidase activity for baicalin conversion, whole-genome sequencing and functional annotation of Lacticaseibacillus rhamnosus HP-B1083 were performed in this study, and its acid tolerance, bile salt tolerance, short-term heat resistance and antibacterial activity were evaluated. The results showed that the strain possessed a circular chromosome with a full length of 3,090,505 bp and a GC content of 46.69%. Gene annotation revealed that the genome contained 2941 coding sequences (CDS) and 112 non-coding RNA genes, including 60 tRNA genes, 1 tmRNA gene, 36 misc_RNA genes and 15 rRNA genes. The functional annotations further reveal that this genome is rich in genes related to carbohydrate metabolism, hydrolases, and transferases, which is highly consistent with its phenotypic characteristics in glycoside transformation and the synthesis of antibacterial substances. In addition, acid tolerance, bile salt tolerance and short-term heat resistance experiments verified that HP-B1083 had acid resistance, bile salt resistance and short-term heat resistance. Antibacterial activity tests confirmed that HP-B1083 produced inhibition zone diameters over 10 mm against common foodborne pathogenic bacteria such as Escherichia coli and Bacillus cereus. Therefore, Lacticaseibacillus rhamnosus HP-B1083 has important application prospects in the development of functional foods, preparation of enzyme preparations and pharmaceutical industry.

Whole Genome Sequencing↗

PubMed2025

Transmission of extended spectrum β-lactamase-producing Escherichia coli and antimicrobial resistance gene flow across One Health compartments in eastern Africa: a whole-genome sequence analysis from a prospective cohort study.

BACKGROUND: The One Health paradigm considers interdependence of human, animal, and environmental health. However, there is little evidence from high-income countries to support the importance of a One Health approach to addressing spread of antimicrobial resistance (AMR). Given AMR is a global threat, understanding how the close interactions of humans with animals and the environment in low-income settings affect the spread of AMR is important. We aimed to investigate diversity and transmission of extended spectrum β-lactamase (ESBL)-producing Escherichia coli across household-linked One Health compartments using genomic data. METHODS: We sequenced whole genomes of ESBL-producing E coli isolates from humans, animals, and the environment from a prospective, longitudinal cohort study conducted in Malawi (April 29, 2019, to Dec 3, 2020) and Uganda (July 16, 2020, to Aug 6, 2021). In the cohort study, 259 households were enrolled at baseline in Malawi and 92 in Uganda from a mix of urban, peri-urban, and rural areas. Households were followed up at months 1, 3, and 6 in Malawi and at months 1, 2, and 4 in Uganda. Samples collected at each visit included human and animal stool, environmental samples from hand-contact areas, food, and water, and broader environmental samples such as river water. Samples were cultured in buffered peptone water and then ESBL chromogenic agar to isolate ESBL-producing E coli. ESBL-producing E coli isolates underwent whole-genome sequencing. We performed phylogenetic analyses, and in-silico multi-locus sequence typing, characterised AMR determinants and linked genotypes with sample location, ecological source, and other covariates. We performed fine-scale single nucleotide polymorphism (SNP) and network analysis to infer strain and plasmid transmission across ecological compartments. The primary outcome was colonisation with ESBL-producing E coli. Secondary outcomes were genomic clusters and ESBL genomic determinants within and between One Health compartments. FINDINGS: We found high diversity of ESBL-producing E coli, with 170 sequence types and 166 genomic clusters identified from 2344 genomes, including 1814 genomes from Malawi (907 human, 221 animal, and 686 environmental) and 530 genomes from Uganda (380 human, 147 animal, and three environmental). Sequence type (ST)131 dominated in Malawi (209 [11·5%] of 1814 genomes), and ST10 dominated in Uganda (45 [8·5%] of 530 genomes). Common ESBL genes blaCTX-M-15 (1604 [68·4%] of 2344 genomes) and blaCTX-M-27 (336 [14·3%] of 2344 genomes) were carried on a complex network of 55 and 30 different plasmids. This diversity of plasmids presented multiple pathways for dissemination and revealed high force of selection. Phylogenetic analyses revealed common intermixing of isolates between humans, animals, and the environment. SNP transmission analysis revealed ecologically overlapping clusters, suggesting ESBL-producing E coli co-circulation both within and between compartments with frequent spillover events. Applying a five-SNP threshold, we inferred 463 human-environment transmission events, 146 human-animal events, and 142 animal-environment events. INTERPRETATION: Our work suggests that a One Health approach is crucial to addressing AMR in eastern Africa. Improving water, sanitation, and hygiene systems will create a safer environment, reduce spillovers of AMR bacteria between compartments, and eventually reduce AMR reservoirs in the environment and in animals. FUNDING: Medical Research Council, National Institute for Health and Care Research, and Wellcome Trust.

Humans↗

PubMed2025

Exploring biosynthetic potential of the endophytic Penicillium turbatum BLH34 using whole-genome sequence analysis and molecular networking.

An in-depth genomic and metabolomic investigation was conducted on the endophytic fungus Penicillium turbatum BLH34, isolated from Macleaya cordata. Hybrid sequencing (Illumina-Nanopore) generated a high-quality 27.9 Mb genome (GC 48.6%) encoding 9798 proteins, with functional annotation linking 5350 genes to the NCBI non-redundant database and 3404 to KEGG pathways. AntiSMASH analysis uncovered 35 biosynthetic gene clusters (BGCs), 23 of which lacked homology to known pathways, highlighting BLH34's potential for novel metabolite discovery. Molecular networking (GNPS) and LC-MS/MS identified 19 specialised metabolites, including antimicrobial polyketides. Bioassays demonstrated potent inhibition against Staphylococcus aureus (36 mm), Bacillus subtilis (28 mm) and Escherichia coli (24 mm), underscoring its pharmaceutical relevance.

Penicillium↗

PubMed2026

Whole-genome sequencing and analysis of the endophytic fungus Alternaria alternata Y-2 from Leymus chinensis.

To explore the genetic basis and functional potential of beneficial symbiosis between the endophytic fungus Alternaria alternata Y-2 and its host Leymus chinensis, we performed Illumina-based draft whole-genome sequencing and systematic bioinformatic analysis. Although this assembly does not reach telomere-to-telomere completeness, it provides high-quality gene-level information for gene prediction, functional annotation, carbohydrate-active enzyme (CAZyme) identification, and secondary metabolite biosynthetic gene cluster analysis. The final genome size of A. alternata Y-2 was 34,383,676 bp with a GC content of 51.0%, containing 12,724 predicted protein-coding genes, 90 tRNAs, and 12 rRNAs. BUSCO assessment showed 98.9% completeness, supporting the high quality of this draft genome. A total of 12,627 genes were successfully annotated in the NCBI NR database, and 17,183 genes were functionally categorized using GO terms. In total, 448 CAZyme genes and 21 secondary metabolite biosynthetic gene clusters were identified, which are potentially involved in lignocellulose degradation, cellular redox homeostasis and biosynthesis of bioactive metabolites. Based on ITS sequence alignment, NR annotation, and phylogenetic analysis of single-copy orthologous genes, the strain was confidently identified as A. alternata. This study firstly reports the draft genome of an endophytic A. alternata strain derived from L. chinensis and provides valuable genetic resources for exploring the endophytic lifestyle, stress tolerance, and bioactive metabolite potential of this fungus.

Alternaria↗

PubMed2026

Whole genome analysis of a multidrug-resistant blaNDM-5-carrying Escherichia coli Sequence Type (ST) 167 strain isolated from seafood in Mumbai, India.

BACKGROUND: E. coli ST167 is an emerging extraintestinal pathogenic Escherichia coli (ExPEC) clone. This study reports the whole genome sequence analysis of a multidrug-resistant, blaNDM-5 harboring E. coli ST167 (EC121) isolated from seafood. The antibiotic susceptibility pattern was determined using the standard disc diffusion method. Genomic DNA was extracted, purified, and sequenced using the Illumina platform. The whole genome sequence was analyzed to determine the genome characteristics, including sequence type, serotype, phylogroup, antibiotic resistance genes, virulence attributes, and phylogenetic analysis. RESULTS: Phenotypically, this isolate was resistant to 26 of the 33 antibiotics tested, which correlated well with in-silico prediction. Multilocus sequence typing (MLST) analysis revealed that this strain belonged to sequence type 167, serotype O101:H9, and phylogroup A and harbored different virulence genes, suggesting it was a potential human pathogen. Many acquired antibiotic resistance genes were detected, including blaNDM-5, blaCMY-42, blaOXA-1, blaTEM-116, catA1, sul2, and tet(B). Point mutations in gyrA and parC responsible for quinolone resistance were also detected. CONCLUSION: The combinations of virulence and antibiotic resistance genes in this strain highlight the significant risk associated with emerging E. coli clonal types contaminating the seafood supply chain. Fecal contamination of seafood can contribute to the community dissemination of multidrug-resistant E. coli, necessitating effective monitoring measures.

Seafood↗

PubMed2025

Acetyl-CoA synthetase mutations affect the susceptibility of Plasmodium falciparum to antimalarial drugs.

Plasmodium falciparum acetyl-CoA synthetase (PfAcAS) is an important source of acetyl-CoA. We detected mutations S868G and V950I in PfAcAS by whole-genome sequencing analysis in certain recrudescent parasites after treatment with artesunate and dihydroartemisinin-piperaquine. Using CRISPR/Cas9 technology, we engineered parasite lines to carry the PfAcAS S868G and V950I mutations in two genetic backgrounds and evaluated their susceptibilities to antimalarial drugs in vitro. The results demonstrated that PfAcAS S868G and V950I mutations alone or in combination affected the susceptibility of P. falciparum to several antimalarial drugs, including the artemisinin derivatives (dihydroartemisinin, artesunate, and artemether) and chloroquine, although absolute changes in susceptibilities were modest.IMPORTANCEMalaria, an infectious disease caused by Plasmodium parasites and transmitted by mosquitoes, continues to be one of the most pressing public health challenges worldwide. P. falciparum has demonstrated reduced sensitivity to artemisinin-based combination therapies (ACTs), thereby intensifying the difficulties associated with malaria management. Currently, only a limited number of molecular markers exist for identifying drug resistance in P. falciparum, and these markers do not fully elucidate the mechanisms behind this resistance. In this study, we performed whole-genome sequencing analysis on P. falciparum strains that reemerged following ACT treatment. We aim to identify molecules potentially associated with drug resistance, which may provide new molecular markers for monitoring drug resistance in P. falciparum.

Plasmodium falciparum↗

PubMed2026

Rare variant analysis of whole genome sequenced juvenile idiopathic arthritis multiplex pedigrees identifies rare variants in NOD2 and ACVR1.

Juvenile idiopathic arthritis is a complex rheumatic disease that is influenced by environmental and genetic factors. Linkage and genome-wide association studies have identified genes that contribute to the risk of developing juvenile idiopathic arthritis but are limited in their ability to identify disease-risk variants of large effect. Penetrant, heritable risk variants can be detected in high-risk families, but such cases are uncommon due to the low prevalence of juvenile idiopathic arthritis. This study utilizes whole-genome sequencing of 23 multiplex families, the largest such cohort to date, to discover variants and genes relevant to JIA pathogenesis. Pathogenic variants in NOD2 associated with Blau syndrome, an ultra-rare Mendelian inflammatory disorder, are the most recurrent variants in the cohort, consistent with previous reports that milder presentations of Blau syndrome are oftentimes misdiagnosed as juvenile idiopathic arthritis. For the first time, however, rare variants in ACVR1 and SMAD6, integral components of the Bone Morphogenic Protein pathway, are found to be associated with juvenile idiopathic arthritis. Identified ACVR1 variants map to critical protein domains. AlphaFold modeling predicts that the ACVR1 interaction with its inhibitor OGT is disrupted by these variants, indicating that the patient-mutated protein has a gain-of-function phenotype. Drosophila melanogaster expressing either a wild-type or patient-mutated version of ACVR1 exhibit embryonic lethality, with the mutant exhibiting 1.4-fold greater lethality than wild-type. The combination of family-based cohorts for gene discovery, AI-based computational tools, and animal model studies for tests of variant function underscores shared disease pathogenesis between JIA and monogenic disorders of immunity and connective tissue.

Arthritis, Juvenile↗

PubMed2026

Genomic epidemiology and antimicrobial resistance profile of Shigella isolated from diarrhoea diseases in under-five children in Blantyre, Malawi.

Antimicrobial resistance (AMR) in Shigella is rising globally, complicating shigellosis management. Whole-genome sequence analysis (WGSA) has advanced our understanding of AMR and transmission dynamics, yet contemporary whole-genome sequencing data from Shigella in sub-Saharan Africa remain scarce. In this study, we applied WGSA to 27 Shigella isolates collected from children presenting with diarrhoea at Ndirande Health Centre in Malawi (2022-2023), as part of the Enterics for Global Health Shigella surveillance study. Serotyping, AMR profiling and phylogenetic analysis revealed Shigella sonnei as the dominant serogroup, with distinct genetic clustering relative to global reference strains among S. sonnei, Shigella flexneri and Shigella boydii. We identified 16 AMR genes linked to ten antimicrobial classes with qnrS1 and qnrB19 genes conferring resistance to fluoroquinolone, alongside IncFIB(K) and IncFII plasmid replicon markers. Importantly, no azithromycin resistance determinants were detected both genotypically and phenotypically, providing baseline evidence that warrants continued surveillance of current first-line treatment. However, the detection of fluoroquinolone resistance genes with plasmid replicon markers in the absence of phenotypic resistance might indicate a silent reservoir with epidemic potential. This is the first contemporary Shigella data from a large-scale diarrhoea disease surveillance study in Malawi, providing essential baseline information for guiding antibiotic treatment and future vaccine development efforts, contributing to the efforts to combat shigellosis in Malawi and other similar regions.

Humans↗

PubMed2025

Clinical carbapenem-resistant Enterobacterales in a University Hospital in Dakar, Senegal: genomic insights into Enterobacter hormaechei ST182 strains carrying blaNDM-5 and blaOXA-48 genes .

Senegal has witnessed the emergence and spread of carbapenem-resistant Enterobacterales (CRE), which often cause deadly infections. Accordingly, this study aimed to determine the antimicrobial susceptibility and prevalence of carbapenemases, as well as to perform a whole-genome sequence analysis of clinical CRE isolates from a university hospital in Dakar, Senegal. MALDI-TOF MS and VITEK2 systems were used for bacterial identification and antimicrobial susceptibility testing (AST). Carbapenemase- and cephalosporinase-encoding genes were screened using simplex end-point polymerase chain reaction. Whole-genome sequencing (WGS) was performed using the Illumina MiSeq platform. The CRE isolates were resistant to almost all the 34 antimicrobials tested. Nevertheless, colistin and amikacin remained active, with susceptibility rates of 96% and 71%, respectively. Only the carbapenemase genes blaOXA-48 (53.8%; 15/28) and blaNDM (35.7%; 10/28) and the cephalosporinase gene blaCMY-1 (25%; 7/28) were identified. In this context, two extensively drug-resistant Enterobacter hormaechei isolates were subjected to WGS analysis. These isolates were assigned as sequence type (ST) 182 and carried several genes related to antimicrobial resistance (AMR), metal tolerance, and virulence. An IncL/M plasmid with 61,054 bp in length was identified as carrying the blaOXA-48 gene, whereas an IncFIB(pECLA)/IncFII(pECLA)/IncX3 mutireplicon plasmid with 217,745 bp in length was detected as harboring the blaNDM-5 gene and other genes related to AMR and metal tolerance. Our study presents the first landscape of clinical CRE circulating in Senegal, along with additional genomic analysis of E. hormaechei ST182 strains, which could be useful for mitigating the burden associated with CRE in this country.IMPORTANCEThe investigation of global critical priority CRE isolates has become crucial to reduce morbidity and mortality associated with AMR. This study revealed that colistin and amikacin can be considered good alternatives for treating CRE-associated infections in Dakar. In addition, the genomic approach revealed that the CRE isolates carried both a wide resistome and virulome. Moreover, the abundance of horizontal gene transfer regions in the genomes suggests the great implications of mobile genetic elements in the spread of AMR in Dakar. Furthermore, this study reported the complete sequences of chromosomes and blaOXA-48 and blaNDM-5-carrying plasmids. Our findings are of great importance because complete genome sequences are still rarely characterized in the West African region. Finally, this study highlights the importance of strengthening genomic surveillance of CRE in sub-Saharan African countries to mitigate the burden associated with these pathogens.

Senegal↗

PubMed2026

Personalized medicine strategy for MPNSTs: using precision oncology on PDOX models to inform tumor boards.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are a heterogeneous group of aggressive soft tissue sarcomas with poor prognosis. Currently there is a lack of effective treatments for MPNSTs. Here, we propose a personalized medicine approach that integrates a precision oncology strategy guided by MPNST genomic analysis, with a functional validation of treatment response in an orthotopic xenograft model (PDOX) derived from the same MPNST. METHODS: Comprehensive whole genome sequencing analysis was performed in primary MPNSTs, relapses and (in one case) metastases, following disease progression in two independent individuals. Matched MPNST PDOX models were generated by orthotopically implanting tumor fragments near the sciatic nerve of immunodeficient mice. Candidate targeted combination therapies were prioritized based on genomic alterations and tested in vivo in the PDOX models. RESULTS: The feasibility of the developed strategy is illustrated for two MPNST patients, one Neurofibromatosis type 1 (NF1) individual that developed two independent MPNSTs and another sporadic MPNST case with multiple metastatic relapses. Genomic analysis revealed a remarkable degree of genomic stability across primary MPNSTs and their successive relapses in each patient, and even metastases in one individual. While based on a small number of cases requiring additional analyses, this finding aligns with previous evidence suggesting a fair genomic conservation throughout tumor evolution. This stability supports the identification of consistent therapeutic vulnerabilities throughout disease progression. Among the therapies tested, co-treatment of MEK inhibitor (MEKi) plus bromodomain inhibitor (BETi) elicited the highest antitumor activity, resulting in approximately 60% tumor volume reduction in the sporadic MPNST PDX model, whose patient has been receiving this therapy for eight months with sustained remission. CONCLUSIONS: This study demonstrates the feasibility and clinical utility of integrating genomic-driven precision oncology with PDOX-based functional testing for MPNSTs. This strategy may support molecular tumor boards (MTBs) in their treatment decisions. The observed genomic stability supports the use of longitudinal tumor profiling to guide treatment, and the success of MEKi+BETi highlights its potential as a combination therapy for MPNSTs.

Precision Medicine↗

PubMed2024

Acquired resistance of Stenotrophomonas maltophilia to antimicrobials induced by herbicide paraquat dichloride.

Stenotrophomonas maltophilia, a ubiquitous environmental bacterium, is an important cause of nosocomial infections. Although banned in some countries, paraquat (PQ) is commonly used to control weeds. In this study, we investigated the effects of increasing concentrations of PQ on S. maltophilia and its antimicrobial resistance. The sequential exposure of S. maltophilia K279a to increasing concentrations of PQ induces the formation of strains with increased resistance to PQ. Among the 400 PQ-resistant isolates tested, 70 clones were resistant to 16 μg/ml ciprofloxacin (CIP), and around 18% of the PQ/CIP-resistant isolates showed increased resistance to all the tested antimicrobials including, the aminoglycosides, quinolones, cephalosporin, chloramphenicol, and co-trimoxazole. The results of the expression analysis of the antimicrobial resistance genes in the five selected PQ/CIP-resistant isolates demonstrated the high expression of genes encoding efflux pumps (smeYZ, smaAB, smaCDEF, smeDEF, smeVWX, and smtcrA) and the enzymes aph(3')-IIc, blaL1, and blaL2. However, expression of the genes known for PQ resistance (i.e., mfsA and sod) were not altered relative to the wild-type levels. Whole genome sequence analysis identified gene mutations that could account for the antimicrobial resistance, namely, smeT (TetR family regulatory protein), rplA (ribosomal protein L1), and acnA (aconitase A). Ectopic expression of wild-type AcnA partially complemented the fluoroquinolone-resistant phenotype of the mutant with mutated acnA, which suggests the role of aconitase A in antimicrobial susceptibility. Exposure of S. maltophilia to PQ thus induces the development of strains that increase resistance to multiple antimicrobials.

Stenotrophomonas maltophilia↗

PubMed2026

Analysis of the genome of a Pseudomonas monsensis isolate that produces the antifungal dipeptide maculosin.

Candida species have been attributed to causing ~647,000 deaths annually. Candida albicans has been identified by the WHO as a priority pathogen for targeted antifungal drug development. To this end, we have screened microbial strains from the public outreach project Swab and Send for anti-Candida activity. This process identified Pseudomonas sp. SS1954.14, which displayed potent activity against C. albicans, both on agar and in a cell-free supernatant assay. Whole-genome sequence analysis identified this strain as Pseudomonas monsensis. It contains several biosynthetic gene clusters, suggesting that it can produce hydrogen cyanide, lokisin, pyoverdine and colicin/carocin, which may contribute to the observed antifungal activity. However, an active compound was separated by preparative high-performance liquid chromatography and identified through high-resolution mass spectrometry as maculosin [cyclo(Pro-Tyr)]. This cyclic dipeptide has previously been found to possess antifungal activity, but the exact biosynthetic mechanism remains undetermined. Reporting this genome alongside the associated evidence of maculosin production represents a valuable resource for biosynthetic investigations.

Candida albicans↗

PubMed2019

Unique genetic basis of the distinct antibiotic potency of high acetic acid production in the probiotic yeast Saccharomyces cerevisiae var. boulardii.

The yeast Saccharomyces boulardii has been used worldwide as a popular, commercial probiotic, but the basis of its probiotic action remains obscure. It is considered conspecific with budding yeast Saccharomyces cerevisiae, which is generally used in classical food applications. They have an almost identical genome sequence, making the genetic basis of probiotic potency in S. boulardii puzzling. We now show that S. boulardii produces at 37°C unusually high levels of acetic acid, which is strongly inhibitory to bacterial growth in agar-well diffusion assays and could be vital for its unique application as a probiotic among yeasts. Using pooled-segregant whole-genome sequence analysis with S. boulardii and S. cerevisiae parent strains, we succeeded in mapping the underlying QTLs and identified mutant alleles of SDH1 and WHI2 as the causative alleles. Both genes contain a SNP unique to S. boulardii (sdh1 F317Y and whi2 S287*) and are fully responsible for its high acetic acid production. S. boulardii strains show different levels of acetic acid production, depending on the copy number of the whi2 S287* allele. Our results offer the first molecular explanation as to why S. boulardii could exert probiotic action as opposed to S. cerevisiae They reveal for the first time the molecular-genetic basis of a probiotic action-related trait in S. boulardii and show that antibacterial potency of a probiotic microorganism can be due to strain-specific mutations within the same species. We suggest that acquisition of antibacterial activity through medium acidification offered a selective advantage to S. boulardii in its ecological niche and for its application as a probiotic.

Acetic Acid↗