101 results on '"Dunyach-Remy C"'
Search Results
2. Genotyping and antifungal susceptibility testing of Cryptococcus neoformans isolates from Cameroonian HIV-positive adult patients
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Bertout, S., Drakulovski, P., Kouanfack, C., Krasteva, D., Ngouana, T., Dunyach-Rémy, C., Dongtsa, J., Aghokeng, A., Delaporte, E., Koulla-Shiro, S., Reynes, J., and Mallié, M.
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- 2013
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3. Faecal carriage of oxyiminocephalosporin-resistant Enterobacteriaceae among paediatric units in different hospitals in the south of France
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Boutet-Dubois, A., Pantel, A., Prère, M.-F., Bellon, O., Brieu-Roche, N., Lecaillon, E., Le Coustumier, A., Davin-Regli, A., Villeneuve, L., Bouziges, N., Gleize, E., Lamarca, R., Dunyach-Remy, C., Sotto, A., and Lavigne, J.-P.
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- 2013
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4. EPS3.09 Biofilm formation in methicillin-resistant Staphylococcus aureus isolated in cystic fibrosis patients is strain-dependent and differentially influenced by antibiotics
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Boudet, A., primary, Sorlin, P., additional, Pouget, C., additional, Chiron, R., additional, Lavigne, J.-P., additional, Dunyach-Remy, C., additional, and Marchandin, H., additional
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- 2021
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5. Dermatoses inflammatoires péri-orificielles, du cuir chevelu et des plis survenant sous anti-TNF dans le cadre des maladies inflammatoires chroniques de l’intestin rôle de Staphylococcus aureus et des carences vitaminiques
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Schwob, E., primary, Dunyach-Remy, C., additional, Lavigne, J.-P., additional, Hoche, S., additional, Dereure, O., additional, Caillo, L., additional, Boivineau, L., additional, Bessis, D., additional, Girard, C., additional, Mura, T., additional, Altwegg, R., additional, and Du-Thanh, A., additional
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- 2020
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6. Link between nasal carriage of Staphylococcus aureus and infected diabetic foot ulcers
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Dunyach-Remy, C., Courtais-Coulon, C., DeMattei, C., Jourdan, N., Schuldiner, S., Sultan, A., Carrière, C., Alonso, S., Sotto, A., and Lavigne, J.-P.
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- 2017
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7. Identification of metabolic biomarkers to follow wound evolution
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Berrou, K., Dunyach-Remy, C., Sanchez, I., Lavigne, JP., Roig, B., Cadiere, Axelle, Détection, évaluation, gestion des risques CHROniques et éMErgents (CHROME) / Université de Nîmes (CHROME), Université de Nîmes (UNIMES), Virulence bactérienne et maladies infectieuses (VBMI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
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[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2017
8. Temporal evolution of bacterial ecology of pressure ulcers in people with spinal cord injury
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Dunyach-Remy, C., primary, Gelis, A., additional, Brunaud, M., additional, Lavigne, J.P., additional, and Sotto, A., additional
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- 2018
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9. CTX-M-15-producing Escherichia coli and the pandemic clone O25b-ST131 isolated from wild fish in Mediterranean Sea
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Brahmi, S., Dunyach-Rémy, C., Touati, A., and Lavigne, J.-P.
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- 2015
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10. Virulence et effets des antibiotiques chez les staphylocoques à coagulase négatives responsables de bactériémies liées au cathéter
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Chatre, C., primary, Dunyach-remy, C., additional, Fournier, R., additional, Marchandin, H., additional, Sotto, A., additional, Reynes, J., additional, and Lavigne, J., additional
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- 2017
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11. Polymerase chain reaction–denaturing gradient gel electrophoresis (PCR–DGGE): A promising tool to diagnose bacterial infections in diabetic foot ulcers
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Dunyach-Remy, C., Cadière, A., Richard, J.-L., Schuldiner, S., Bayle, S., Roig, B., Sotto, A., and Lavigne, J.-P.
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- 2014
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12. Existence of a Colonizing Staphylococcus aureus Strain Isolated in Diabetic Foot Ulcers
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Messad, N., Prajsnar, T.K., Lina, G., O'Callaghan, D., Foster, S.J., Renshaw, S.A., Skaar, E.P., Bes, M., Dunyach-Remy, C., Vandenesch, F., Sotto, A., and Lavigne, J.-P.
- Abstract
Staphylococcus aureus is an opportunistic bacterium capable of causing a wide range of severe diseases when it gains access to underlying tissues. Paradoxically, S. aureus is a common inhabitant of the skin microflora and colonizes the nares and other human mucosa. The purpose of this study was to determine the genetic basis for the differences in the pathogenic versus colonizing potential of S. aureus isolated from diabetic foot ulcers (DFUs). By performing optical map comparisons of a collection of S. aureus strains isolated from DFUs, we brought to light a prophage present in noninfecting bacteria. The phage, namely ROSA-like, was localized in a hotspot region ΦNM2 near the locus isd, the iron surface determinant system. The integrated phage significantly reduces the virulence of the strain and increases the biofilm formation. DFUs seem to be a specific niche of this colonizing strain. The ROSA-like phage represents the first description of a mobile element present mainly in S. aureus isolated from DFUs, which modulates the relationship of the bacteria with its human host. This phage appears to attenuate bacterial virulence and promote colonization.
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- 2015
13. Apport de la DGGE dans le diagnostic microbiologique dans les plaies du pied chez le diabétique. 3
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Dunyach-Remy, C., Cadiere, A., Richard, J.L., Roig, B., Sotto, A., Lavigne, J.P., Cadiere, Axelle, Détection, évaluation, gestion des risques CHROniques et éMErgents (CHROME) / Université de Nîmes (CHROME), and Université de Nîmes (UNIMES)
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[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2013
14. Étude d’activité in vitro et de stabilité de suspensions antifongiques pour bain de bouche : vers une remise en question de pratiques empiriques ?
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Jolivot, P.A., primary, Dunyach-Remy, C., additional, Roussey, A., additional, Jalabert, A., additional, Mallié, M., additional, and Hansel-Esteller, S., additional
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- 2012
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15. Dermatoses inflammatoires péri-orificielles, du cuir chevelu et des plis survenant sous anti-TNF dans le cadre des maladies inflammatoires chroniques de l’intestin rôle de Staphylococcus aureuset des carences vitaminiques
- Author
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Schwob, E., Dunyach-Remy, C., Lavigne, J.-P., Hoche, S., Dereure, O., Caillo, L., Boivineau, L., Bessis, D., Girard, C., Mura, T., Altwegg, R., and Du-Thanh, A.
- Abstract
Les manifestations cutanées inflammatoires des patients atteints d’une maladie inflammatoire chronique de l’intestin (MICI) traités par anti-TNF affectent environ 1 patient sur 5. La survenue de lésions cutanées péri-orificielles, érosives, fissuraires et impétiginisées est mal comprise. L’objectif de ce travail était de décrire une série de cas de dermatoses inflammatoires péri-orificielles, survenant sous anti-TNF chez des patients MICI et d’évaluer à l’aide d’une population témoin, si la colonisation des gîtes par Staphylococcus aureus(S. aureus) ou la présence de carences vitaminiques étaient des facteurs de risque d’apparition de ces lésions.
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- 2020
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16. Interactions between Helcococcus kunzii and Staphylococcus aureus: How a commensal bacterium modulates the virulence and metabolism of a pathogen in a chronic wound in vitro model.
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Durand BARN, Daher R, Grenga L, Morsli M, Armengaud J, Lavigne JP, and Dunyach-Remy C
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- Virulence, Proteomics, Staphylococcal Infections microbiology, Quorum Sensing, Gene Expression Regulation, Bacterial, Humans, Symbiosis, Trans-Activators metabolism, Trans-Activators genetics, Microbial Interactions, Virulence Factors genetics, Virulence Factors metabolism, Proteome, Cell Wall metabolism, Staphylococcus aureus pathogenicity, Staphylococcus aureus genetics, Staphylococcus aureus metabolism, Bacterial Proteins metabolism, Bacterial Proteins genetics
- Abstract
Background: Staphylococcus aureus is the predominant pathogen isolated in diabetic foot infections. Recently, the skin commensal bacterium, Helcococcus kunzii, was found to modulate the virulence of this pathogen in an in vivo model. This study aims to elucidate the molecular mechanisms underlying the interaction between these two bacterial species, using a proteomic approach., Results: Our results reveal that H. kunzii can coexist and proliferate alongside S. aureus in a Chronic Wound Media (CWM), thereby mimicking an in vitro chronic wound environment. We noted that the secreted proteome of H. kunzii induced a transcriptional effect on S. aureus virulence, resulting in a decrease in the expression level of agrA, a gene involved in quorum sensing. The observed effect could be ascribed to specific proteins secreted by H. kunzii including polysaccharide deacetylase, peptidoglycan DD-metalloendopeptidase, glyceraldehyde-3-phosphate dehydrogenase, trypsin-like peptidase, and an extracellular solute-binding protein. These proteins potentially interact with the agr system, influencing S. aureus virulence. Additionally, the virulence of S. aureus was notably affected by modifications in iron-related pathways and components of cell wall architecture in the presence of H. kunzii. Furthermore, the overall metabolism of S. aureus was reduced when cocultured with H. kunzii., Conclusion: Future research will focus on elucidating the role of these excreted factors in modulating virulence., (© 2024. The Author(s).)
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- 2024
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17. Investigation of PhoP response regulator inhibition to overcome resistance in Gram-negative clinical bacteria.
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Majdi C, Duvauchelle V, Seghir M, Bénimélis D, Dunyach-Remy C, Dessolin J, Meffre P, and Benfodda Z
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- Humans, Drug Resistance, Bacterial, Gram-Negative Bacteria drug effects, Anti-Bacterial Agents pharmacology, Bacterial Proteins genetics, Bacterial Proteins metabolism, Microbial Sensitivity Tests
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- 2024
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18. Emergence of multidrug-resistant Staphylococcus haemolyticus in neonatal intensive care unit in Southern France, a genomic study.
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Magnan C, Morsli M, Salipante F, Thiry B, Attar JE, Maio MD, Safaria M, Tran TA, Dunyach-Remy C, Ory J, Richaud-Morel B, Sotto A, Pantel A, and Lavigne JP
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- Humans, France epidemiology, Infant, Newborn, Female, Male, Case-Control Studies, Microbial Sensitivity Tests, Cross Infection microbiology, Cross Infection epidemiology, Genotype, Risk Factors, Genome, Bacterial, Staphylococcus haemolyticus genetics, Staphylococcus haemolyticus drug effects, Staphylococcus haemolyticus isolation & purification, Staphylococcus haemolyticus classification, Intensive Care Units, Neonatal, Staphylococcal Infections microbiology, Staphylococcal Infections epidemiology, Drug Resistance, Multiple, Bacterial genetics, Anti-Bacterial Agents pharmacology, Whole Genome Sequencing
- Abstract
An emergence of multidrug-resistant (MDR) Staphylococcus haemolyticus has been observed in the neonatal intensive care unit (NICU) of Nîmes University Hospital in southern France. A case-control analysis was conducted on 96 neonates, to identify risk factors associated with S. haemolyticus infection, focusing on clinical outcomes. Forty-eight MDR S. haemolyticus strains, isolated from neonates between October 2019 and July 2022, were investigated using routine in vitro procedures and whole-genome sequencing. Additionally, five S. haemolyticus isolates from adult patients were sequenced to identify clusters circulating within the hospital environment. The incidence of neonatal S. haemolyticus was significantly associated with low birth weight, lower gestational age, and central catheter use ( p < 0.001). Sepsis was the most frequent clinical manifestation in this series (20/46, 43.5%) and was associated with five deaths. Based on whole-genome analysis, three S. haemolyticus genotypes were predicted: ST1 (6/53, 11%), ST25 (3/53, 5.7%), and ST29 (44/53, 83%), which included the subcluster II-A, predominantly emerging in the neonatal department. All strains were profiled in silico to be resistant to methicillin, erythromycin, aminoglycosides, and fluoroquinolones, consistent with in vitro antibiotic susceptibility tests. Moreover, in silico prediction of biofilm formation and virulence-encoding genes supported the association of ST29 with severe clinical outcomes, while the persistence in the NICU could be explained by the presence of antiseptic and heavy metal resistance-encoding genes. The clonality of S. haemolyticus ST29 subcluster II-A isolates confirms healthcare transmission causing severe infections. Based on these results, reinforced hygiene measures are necessary to eradicate the nosocomial transmission of MDR strains.
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- 2024
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19. Early detection of pancreatic cancer by liquid biopsy "PANLIPSY": a french nation-wide study project.
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Bardol T, Dujon AM, Taly V, Dunyach-Remy C, Lavigne JP, Costa-Silva B, Kurma K, Eslami-S Z, Cayrefourcq L, Canivet C, Muscari F, Bournet B, and Alix-Panabières C
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- Aged, Female, Humans, Male, Middle Aged, France, Liquid Biopsy methods, Prospective Studies, Biomarkers, Tumor blood, Carcinoma, Pancreatic Ductal blood, Carcinoma, Pancreatic Ductal diagnosis, Carcinoma, Pancreatic Ductal pathology, Early Detection of Cancer methods, Pancreatic Neoplasms blood, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms pathology
- Abstract
Background: Pancreatic cancer, predominantly characterized by ductal adenocarcinoma (PDAC) accounts for 90% of cases and is the fourth leading cause of cancer-related deaths globally. Its incidence is notably increasing. This poor prognosis is primarily due to late-stage diagnosis (approximately 70% to 80% of patients are diagnosed at an advanced stage), aggressive tumor biology, and low sensitivity to chemotherapy. Consequently, it is crucial to identify and develop a simple, feasible and reproducible blood-based signature (i.e., combination of biomarkers) for early detection of PDAC., Methods: The PANLIPSY study is a multi-center, non-interventional prospective clinical trial designed to achieve early detection of PDAC with high specificity and sensitivity, using a combinatorial approach in blood samples. These samples are collected from patients with resectable, borderline or locally advanced, and metastatic stage PDAC within the framework of the French Biological and Clinical Database for PDAC cohort (BACAP 2). All partners of the BACAP consortium are eligible to participate. The study will include 215 PDAC patients, plus 25 patients with benign pancreatic conditions from the PAncreatic Disease Cohort of TOuLouse (PACTOL) cohort, and 115 healthy controls, totaling 355 individuals. Circulating biomarkers will be collected in a total volume of 50 mL of blood, divided into one CellSave tube (10 mL), two CELL-FREE DNA BCT® preservative tubes (18 mL), and five EDTA tubes (22 mL in total). Samples preparation will adhere to the guidelines of the European Liquid Biopsy Society (ELBS). A unique feature of the study is the AI-based comparison of these complementary liquid biopsy biomarkers. Main end-points: i) to define a liquid biopsy signature that includes the most relevant circulating biomarkers, ii) to validate the multi-marker panel in an independent cohort of healthy controls and patients, with resectable PDAC, and iii) to establish a unique liquid biopsy biobank for PDAC study., Discussion: The PANLIPSY study is a unique prospective non-interventional clinical trial that brings together liquid biopsy experts. The aim is to develop a biological signature for the early detection of PDAC based on AI-assisted detection of circulating biomarkers in blood samples (CTCs, ctDNA, EVs, circulating immune system, circulating cell-free nucleosomes, proteins, and microbiota)., Trial Registration: ClinicalTrials.gov Identifier: NCT06128343 / NCT05824403. Registration dates: June 8,2023 and April 21, 2023., (© 2024. The Author(s).)
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- 2024
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20. Direct metagenomics investigation of non-surgical hard-to-heal wounds: a review.
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Morsli M, Salipante F, Magnan C, Dunyach-Remy C, Sotto A, and Lavigne JP
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- Humans, Wound Healing, Microbiota genetics, Pressure Ulcer microbiology, Diabetic Foot microbiology, Wound Infection microbiology, Varicose Ulcer microbiology, Metagenomics methods, Bacteria genetics, Bacteria isolation & purification, Bacteria classification, High-Throughput Nucleotide Sequencing
- Abstract
Background: Non-surgical chronic wounds, including diabetes-related foot diseases (DRFD), pressure injuries (PIs) and venous leg ulcers (VLU), are common hard-to-heal wounds. Wound evolution partly depends on microbial colonisation or infection, which is often confused by clinicians, thereby hampering proper management. Current routine microbiology investigation of these wounds is based on in vitro culture, focusing only on a limited panel of the most frequently isolated bacteria, leaving a large part of the wound microbiome undocumented., Methods: A literature search was conducted on original studies published through October 2022 reporting metagenomic next generation sequencing (mNGS) of chronic wound samples. Studies were eligible for inclusion if they applied 16 S rRNA metagenomics or shotgun metagenomics for microbiome analysis or diagnosis. Case reports, prospective, or retrospective studies were included. However, review articles, animal studies, in vitro model optimisation, benchmarking, treatment optimisation studies, and non-clinical studies were excluded. Articles were identified in PubMed, Google Scholar, Web of Science, Microsoft Academic, Crossref and Semantic Scholar databases., Results: Of the 3,202 articles found in the initial search, 2,336 articles were removed after deduplication and 834 articles following title and abstract screening. A further 14 were removed after full text reading, with 18 articles finally included. Data were provided for 3,628 patients, including 1,535 DRFDs, 956 VLUs, and 791 PIs, with 164 microbial genera and 116 species identified using mNGS approaches. A high microbial diversity was observed depending on the geographical location and wound evolution. Clinically infected wounds were the most diverse, possibly due to a widespread colonisation by pathogenic bacteria from body and environmental microbiota. mNGS data identified the presence of virus (EBV) and fungi (Candida and Aspergillus species), as well as Staphylococcus and Pseudomonas bacteriophages., Conclusion: This study highlighted the benefit of mNGS for time-effective pathogen genome detection. Despite the majority of the included studies investigating only 16 S rDNA, ignoring a part of viral, fungal and parasite colonisation, mNGS detected a large number of bacteria through the included studies. Such technology could be implemented in routine microbiology for hard-to-heal wound microbiota investigation and post-treatment wound colonisation surveillance., (© 2024. The Author(s).)
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- 2024
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21. Correction: Usefulness of dynamic regression time series models for studying the relationship between antimicrobial consumption and bacterial antimicrobial resistance in hospitals: a systematic review.
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Laffont-Lozes P, Larcher R, Salipante F, Leguelinel-Blache G, Dunyach-Remy C, Lavigne JP, Sotto A, and Loubet P
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- 2024
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22. Evolution of the urinary microbiota in spinal cord injury patients with decubitus ulcer: A snapshot study.
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Morsli M, Salipante F, Gelis A, Magnan C, Guigon G, Lavigne JP, Sotto A, and Dunyach-Remy C
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- Humans, Prospective Studies, Pressure Ulcer complications, Spinal Cord Injuries complications, Microbiota
- Abstract
Current microbiome investigations of patients with pressure ulcers (PU) are mainly based on wound swabs and/or biopsy sequencing, leaving the colonization scenario unclear. Urinary microbiota has been never studied. As a part of the prospective ESCAFLOR study, we studied urinary microbiota of spinal cord injury (SCI) patients with PU without any urinary tract infection at the inclusion, collected at two times (at admission [D0] and after 28 days [D28]) during the patient's care, investigated by 16S rDNA metagenomics next generation sequencing. Subgroup analyses were carried out between patients with wounds showing improved evolution versus stagnated/worsened wounds at D28. Analysis was done using EPISEQ® 16S and R software. Among the 12 studied patients, the urinary microbiota of patients with improved wound evolution at D28 (n = 6) presented a significant decrease of microbial diversity. This modification was associated with the presence of Proteobacteria phylum and an increase of Escherichia-Shigella (p = 0.005), as well as the presence of probiotic anaerobic bacteria Lactobacillus and Bifidobacterium. In contrast, Proteus abundance was significantly increased in urine of patients with stagnated/worsened wound evolution (n = 6) (p = 0.003). This study proposes urinary microbiota as a complementary factor indirectly associated with the wound evolution and patient cure. It opens new perspectives for further investigations based on multiple body microbiome comparison to describe the complete scenario of the transmission dynamics of wound-colonizing microorganisms., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)
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- 2024
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23. The ROSA-Like Prophage Colonizing Staphylococcus aureus Promotes Intracellular Survival, Biofilm Formation, and Virulence in a Chronic Wound Environment.
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Ahmad-Mansour N, Plumet L, Pouget C, Kissa K, Dunyach-Remy C, Sotto A, Lavigne JP, and Molle V
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- Animals, Staphylococcus aureus, Virulence, Prophages genetics, Zebrafish, Biofilms, Rosa, Diabetic Foot microbiology, Staphylococcal Infections microbiology
- Abstract
Background: The transition from colonization to invasion is critical in diabetic foot ulcer (DFU). Staphylococcus aureus can colonize DFU, or invade the underlying tissues, causing serious infections. The ROSA-like prophage has previously been implicated in strain colonization characteristics of S aureus isolates in uninfected ulcers., Methods: In this study, we investigated this prophage in the S aureus-colonizing strain using an in vitro chronic wound medium mimicking the chronic wound environment., Results: Chronic wound medium reduced bacterial growth and increased biofilm formation and virulence in a zebrafish model., Conclusions: The ROSA-like prophage promoted intracellular survival of S aureus-colonizing strain in macrophages, keratinocytes, and osteoblasts., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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24. Role of gut microbiota and bacterial translocation in acute intestinal injury and mortality in patients admitted in ICU for septic shock.
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Magnan C, Lancry T, Salipante F, Trusson R, Dunyach-Remy C, Roger C, Lefrant JY, Massanet P, and Lavigne JP
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- Adult, Female, Humans, Bacterial Translocation, Lactation, Intensive Care Units, Hospitalization, Bacteria genetics, Shock, Septic, Gastrointestinal Microbiome
- Abstract
Introduction: Sepsis is a life-threatening organ dysfunction with high mortality rate. The gut origin hypothesis of multiple organ dysfunction syndrome relates to loss of gut barrier function and the ensuing bacterial translocation. The aim of this study was to describe the evolution of gut microbiota in a cohort of septic shock patients over seven days and the potential link between gut microbiota and bacterial translocation., Methods: Sixty consecutive adult patients hospitalized for septic shock in intensive care units (ICU) were prospectively enrolled. Non-inclusion criteria included patients with recent or scheduled digestive surgery, having taken laxatives, pre- or probiotic in the previous seven days, a progressive digestive neoplasia, digestive lymphoma, chronic inflammatory bowel disease, moribund patient, and pregnant and lactating patients. The primary objective was to evaluate the evolution of bacterial diversity and richness of gut microbiota during seven days in septic shock. Epidemiological, clinical and biological data were gathered over seven days. Gut microbiota was analyzed through a metagenomic approach. 100 healthy controls were selected among healthy blood donors for reference basal 16S rDNA values., Results: Significantly lower bacterial diversity and richness was observed in gut microbiota of patients at Day 7 compared with Day 0 (p<0.01). SOFA score at Day 0, Acute Gastrointestinal Injury (AGI) local grade, septic shock origin and bacterial translocation had an impact on alpha diversity. A large increase in Enterococcus genus was observed at Day 7 with a decrease in Enterobacterales, Clostridiales, Bifidobacterium and other butyrate-producing bacteria., Discussion: This study shows the importance of bacterial translocation during AGI in septic shock patients. This bacterial translocation decreases during hospitalization in ICUs in parallel to the decrease of microbiota diversity. This work highlights the role of gut microbiota and bacterial translocation during septic shock., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Magnan, Lancry, Salipante, Trusson, Dunyach-Remy, Roger, Lefrant, Massanet and Lavigne.)
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- 2023
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25. Usefulness of dynamic regression time series models for studying the relationship between antimicrobial consumption and bacterial antimicrobial resistance in hospitals: a systematic review.
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Laffont-Lozes P, Larcher R, Salipante F, Leguelinel-Blache G, Dunyach-Remy C, Lavigne JP, Sotto A, and Loubet P
- Subjects
- Humans, Time Factors, Drug Resistance, Bacterial, Carbapenems, Fluoroquinolones, Hospitals, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Anti-Infective Agents
- Abstract
Backgroung: Antimicrobial resistance (AMR) is on the rise worldwide. Tools such as dynamic regression (DR) models can correlate antimicrobial consumption (AMC) with AMR and predict future trends to help implement antimicrobial stewardship programs (ASPs)., Main Body: We carried out a systematic review of the literature up to 2023/05/31, searching in PubMed, ScienceDirect and Web of Science. We screened 641 articles and finally included 28 studies using a DR model to study the correlation between AMC and AMR at a hospital scale, published in English or French. Country, bacterial species, type of sampling, antimicrobials, study duration and correlations between AMC and AMR were collected. The use of β-lactams was correlated with cephalosporin resistance, especially in Pseudomonas aeruginosa and Enterobacterales. Carbapenem consumption was correlated with carbapenem resistance, particularly in Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Fluoroquinolone use was correlated with fluoroquinolone resistance in Gram-negative bacilli and methicillin resistance in Staphylococcus aureus. Multivariate DR models highlited that AMC explained from 19 to 96% of AMR variation, with a lag time between AMC and AMR variation of 2 to 4 months. Few studies have investigated the predictive capacity of DR models, which appear to be limited., Conclusion: Despite their statistical robustness, DR models are not widely used. They confirmed the important role of fluoroquinolones, cephalosporins and carbapenems in the emergence of AMR. However, further studies are needed to assess their predictive capacity and usefulness for ASPs., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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26. Proteomic insights into Helcococcus kunzii in a diabetic foot ulcer-like environment.
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Durand BARN, Dunyach-Remy C, El Kaddouri O, Daher R, Lavigne JP, Armengaud J, and Grenga L
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- Humans, Proteome genetics, Staphylococcus aureus, Proteomics, Diabetic Foot, Gram-Positive Cocci, Diabetes Mellitus
- Abstract
Purpose: Helcococcus kunzii is a skin commensal, Gram-positive bacterium, mostly isolated from infected chronic wounds. This opportunistic pathogen is usually co-isolated with Staphylococcus aureus. The present dataset explores the production and secretion of H. kunzii bacterial virulence interacting proteins in a growth medium mimicking chronic wounds in exponential and stationary growth phases., Experimental Design: The H. kunzii cellular proteome and exoproteome were assessed by analyzing three biological replicates per condition tested. Samples were analyzed using a Q-Exactive HF mass spectrometer. Comparative and functional analyses were performed to profile the identified protein set., Results: The H. kunzii's cellular proteome encompassed 969 proteins, among which 64 and 53 were specifically identified in the exponential and stationary phase of growth, respectively. Its exoproteome comprised 58 proteins, among which 16 and 14 were characteristic of each growth stage. Metabolic differences between the two phases of growth are discussed. Besides, the production of previously shortlisted and novel putative H. kunzii targets involved in modulating the virulence of S. aureus is investigated., Conclusion and Clinical Relevance: This work, pioneering the study of H. kunzii physiology in a chronic wound-like environment, should assist future research on this opportunistic pathogen and the search for innovative approaches for wound management., (© 2023 The Authors. Proteomics - Clinical Applications published by Wiley-VCH GmbH.)
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- 2023
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27. Effect of antimicrobial consumption on Escherichia coli resistance: assessment and forecasting using Dynamic Regression models in a French university hospital (2014-2019).
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Laffont-Lozes P, Salipante F, Leguelinel-Blache G, Dunyach-Remy C, Lavigne JP, Sotto A, and Larcher R
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- Humans, Escherichia coli, beta-Lactamase Inhibitors pharmacology, Retrospective Studies, Drug Resistance, Multiple, Bacterial, Fluoroquinolones pharmacology, Fluoroquinolones therapeutic use, Hospitals, University, Penicillins pharmacology, Penicillins therapeutic use, Drug Resistance, Bacterial, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Escherichia coli Infections drug therapy, Escherichia coli Infections epidemiology
- Abstract
Introduction: The aim of this study was to determine the correlation between antimicrobial consumption (AMC) and antimicrobial resistance (AMR) in Escherichia coli at a hospital level, and assess the capacity of dynamic regression (DR) models to predict AMR for their use in deployment of antimicrobial stewardship programs (ASPs)., Methods: A retrospective epidemiological study was conducted in a French tertiary hospital between 2014 and 2019. DR models were used to assess the correlation between AMC and AMR from 2014 to 2018. The predictive abilities of the models were estimated by comparing the predicted data with those observed in 2019., Results: Rates of fluoroquinolone and cephalosporin resistance decreased. AMC increased overall but decreased for fluoroquinolone. DR models highlighted that the decrease in use of fluoroquinolone and the increase in use of anti-pseudomonal activity penicillin with beta-lactamase inhibitor (AAPBI) explained 54% of the decrease in fluoroquinolone resistance and 15% of the decrease in cephalosporin resistance. In addition, penicillin/beta-lactamase inhibitor (PBI) consumption explained 53% of PBI resistance, and beta-lactam use explained 36% of penicillin resistance, with both remaining stable over time. DR models had predictive capabilities with margins of error from 8% to 34%., Conclusion: Over a six-year period in a French tertiary hospital, decreasing rates of resistance to fluoroquinolones and cephalosporins were correlated with decreasing use of fluoroquinolone and increasing use of AAPBI, whereas rates of resistance to penicillin remained high and stable. The results indicate that DR models should be used with caution for AMR forecasting and ASP implementation., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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28. Antimicrobial activity of antibiotics on biofilm formed by Staphylococcus aureus and Pseudomonas aeruginosa in an open microfluidic model mimicking the diabetic foot environment.
- Author
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Pouget C, Pantel A, Dunyach-Remy C, Magnan C, Sotto A, and Lavigne JP
- Subjects
- Humans, Anti-Bacterial Agents pharmacology, Staphylococcus aureus, Pseudomonas aeruginosa, Ceftazidime, Microfluidics, Biofilms, Diabetic Foot microbiology, Daptomycin, Staphylococcal Infections microbiology, Diabetes Mellitus
- Abstract
Background: Diabetic foot infections (DFIs) represent a public health problem because of their frequency and the severity of their consequences, i.e. amputation and mortality. Polymicrobial biofilms on the skin surface of these ulcers complicate wound healing. Few in vitro models exist to study the antibiotics activity in this context., Objectives: This study evaluated the in vitro activity of antibiotics against the two main bacteria isolated in DFI, Staphylococcus aureus and Pseudomonas aeruginosa, using a dynamic system (BioFlux™ 200) and a chronic wound-like medium (CWM) that mimic the foot ulcer environment., Methods: Reference strains and two pairs of clinical S. aureus and P. aeruginosa isolated together from a DFI were cultivated in brain heart infusion and CWM media during 72 h at 37°C, alone and combined in the BioFlux™ 200 system. Antibiotic activity was evaluated after a mechanical debridement. The activities were measured by the reduction of biofilm percentage of bacteria in the microfluidic system using microscopy., Results: Daptomycin for S. aureus and ceftazidime for P. aeruginosa showed excellent activity to reduce biofilm biomass, whereas linezolid action was more mitigated and dalbavancin was ineffective. Ceftazidime + daptomycin presented the most potent in vitro activity on a mixed biofilm., Conclusions: The combination of CWM and the BioFlux™ microfluidic system represents a valuable tool to screen the potential antimicrobial activity of antibiotics under conditions mimicking those encountered in DFI. It could help clinicians in their management of chronic wounds., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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29. Dynamics of community-acquired meningitis syndrome outbreaks in southern France.
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Morsli M, Salipante F, Kerharo Q, Boudet A, Stephan R, Dunyach-Remy C, Zandotti C, Lavigne JP, and Drancourt M
- Abstract
In southern France, cases of community-acquired meningitis syndrome (CAM) are typically clustered as outbreaks with determinants which remain unknown. This 61-month retrospective investigation in Nîmes and Marseille university hospital laboratories, yielded 2,209/20,779 (10.63%) documented CAM cases caused by 62 different micro-organisms, represented by seasonal viral etiologies (78.8%), including Enterovirus, Herpes Simplex Virus (HSV), and Varicella-Zoster Virus (VZV; 1,620/2,209 = 73.4%). Multi correspondence analysis revealed an association of infection with age and sex, with the risk of infection being relatively higher in young men, as confirmed by Fisher's exact test ( p < 10
-3 ). Bacterial meningitis accounted for 20% of cases, mostly caused by Streptococcus pneumoniae (27.4% of cases), Neisseria meningitidis (12.5%), and Haemophilus influenzae (9.5%) with bacteria/virus coinfection (0.9%), and only six cases of documented fungal meningitis. In total, 62.6% of cases, of which 88.7% were undocumented, arose from 10 outbreaks. 33.2% of undocumented cases were aged >60 years compared to 19.2% of documented cases ( p < 0.001), and viral infection was more common in the summer (87.5%) compared to other seasons (72.3%; p < 0.001). Outbreaks most often started in Nîmes and moved eastward toward Marseille at a speed of ~9 km/day, and these dynamics significantly correlated with atmospheric temperature, especially during summer outbreaks. In particular, the incidence of Enterovirus-driven outbreaks correlated with temperature, revealing correlation coefficients of 0.64 in Nîmes and 0.72 in Marseille, and its occurrence in Marseille lagged that in Nîmes by 1-2 weeks. Tracing the dynamics of CAM outbreak during this retrospective investigation in southern France yielded a speed of displacement that correlated with the variation in temperature between both cities, and these results provide clues for the next occurrence of undocumented outbreaks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Morsli, Salipante, Kerharo, Boudet, Stephan, Dunyach-Remy, Zandotti, Lavigne and Drancourt.)- Published
- 2023
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30. Effect of Antibiotic Exposure on Staphylococcus epidermidis Responsible for Catheter-Related Bacteremia.
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Pouget C, Chatre C, Lavigne JP, Pantel A, Reynes J, and Dunyach-Remy C
- Subjects
- Humans, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Vancomycin pharmacology, Staphylococcus epidermidis, Catheters microbiology, Microbial Sensitivity Tests, Biofilms, Daptomycin pharmacology, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Bacteremia drug therapy, Bacteremia microbiology
- Abstract
Coagulase-negative staphylococci (CoNS) and especially Staphylococcus epidermidis are responsible for health care infections, notably in the presence of foreign material (e.g., venous or central-line catheters). Catheter-related bacteremia (CRB) increases health care costs and mortality. The aim of our study was to evaluate the impact of 15 days of antibiotic exposure (ceftobiprole, daptomycin, linezolid and vancomycin) at sub-inhibitory concentration on the resistance, fitness and genome evolution of 36 clinical strains of S. epidermidis responsible for CRB. Resistance was evaluated by antibiogram, the ability to adapt metabolism by the Biofilm Ring test
® and the in vivo nematode virulence model. The impact of antibiotic exposure was determined by whole-genome sequencing (WGS) and biofilm formation experiments. We observed that S. epidermidis strains presented a wide variety of virulence potential and biofilm formation. After antibiotic exposure, S. epidermidis strains adapted their fitness with an increase in biofilm formation. Antibiotic exposure also affected genes involved in resistance and was responsible for cross-resistance between vancomycin, daptomycin and ceftobiprole. Our data confirmed that antibiotic exposure modified bacterial pathogenicity and the emergence of resistant bacteria.- Published
- 2023
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31. Phenotypic and Genotypic Virulence Characterisation of Staphylococcus pettenkoferi Strains Isolated from Human Bloodstream and Diabetic Foot Infections.
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Magnan C, Ahmad-Mansour N, Pouget C, Morsli M, Huc-Brandt S, Pantel A, Dunyach-Remy C, Sotto A, Molle V, and Lavigne JP
- Subjects
- Humans, Animals, Virulence genetics, Zebrafish, Phylogeny, Staphylococcus genetics, Biofilms, Anti-Bacterial Agents, Diabetic Foot microbiology, Staphylococcal Infections microbiology, Communicable Diseases, Diabetes Mellitus
- Abstract
Staphylococcus pettenkoferi is a recently described coagulase-negative Staphylococcus identified in human diseases, especially in infections of foot ulcers in patients living with diabetes mellitus. To date, its pathogenicity remains underexplored. In this study, whole-genome analysis was performed on a collection of 29 S. pettenkoferi clinical strains isolated from bloodstream and diabetic foot infections with regard to their phylogenetic relationships and comprehensive analysis of their resistome and virulome. Their virulence was explored by their ability to form biofilm, their growth kinetics and in an in vivo zebrafish embryo infection model. Our results identified two distinct clades (I and II) and two subclades (I-a and I-b) with notable genomic differences. All strains had a slow bacterial growth. Three profiles of biofilm formation were noted, with 89.7% of isolates able to produce biofilm and harbouring a high content of biofilm-encoding genes. Two virulence profiles were also observed in the zebrafish model irrespective of the strains' origin or biofilm profile. Therefore, this study brings new insights in S. pettenkoferi pathogenicity.
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- 2022
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32. Real-time metagenomics-based diagnosis of community-acquired meningitis: A prospective series, southern France.
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Morsli M, Boudet A, Kerharo Q, Stephan R, Salipante F, Dunyach-Remy C, Houhamdi L, Fournier PE, Lavigne JP, and Drancourt M
- Subjects
- Anti-Bacterial Agents, Bacteria genetics, Escherichia coli genetics, Haemophilus influenzae genetics, Humans, Multilocus Sequence Typing, Multiplex Polymerase Chain Reaction methods, Streptococcus pneumoniae genetics, Meningitis, Bacterial diagnosis, Neisseria meningitidis genetics
- Abstract
Background: Point-Of-Care (POC) diagnosis of life-threatening community-acquired meningitis currently relies on multiplexed RT-PCR assays, that lack genotyping and antibiotic susceptibility profiling. We assessed the usefulness of real-time metagenomics (RTM) directly applied to the cerebrospinal fluid (CSF) for the identification, typing and susceptibility profiling of pathogens responsible for community-acquired meningitis., Methods: A series of 52 CSF samples from patients suspected of having community-acquired meningitis, were investigated at POC by direct RTM in parallel to routine real-time multiplex PCR (RT-PCR) and bacterial culture, for the detection of pathogens. RTM-generated sequences were blasted in real-time against an in-house database incorporating the panel of 12 most prevalent pathogens and against NCBI using EPI2ME online software, for pathogen identification. In-silico antibiogram and genotype prediction were determined using the ResFinder bio-tool and MLST online software., Findings: Over eight months, routine multiplex RT-PCR yielded 49/52 positive CSFs, including 21 Streptococcus pneumoniae, nine Neisseria meningitidis, eight Haemophilus influenzae, three Streptococcus agalactiae, three Herpesvirus-1, two Listeria monocytogenes, and one each of Escherichia coli, Staphylococcus aureus and Varicella-Zoster Virus. Parallel RTM agreed with the results of 47/52 CSFs and revealed two discordant multiplex RT-PCR false positives, one H. influenzae and one S. pneumoniae. Both multiplex RT-PCR and RTM agreed on the negativity of three CSFs. While multiplex RT-PCR routinely took 90 min, RTM took 120 min, although the pipeline analysis detected the pathogen genome after 20 min of sequencing in 33 CSF samples; and after two hours in 14 additional CSFs; yielding > 50% genome coverage in 19 CSFs. RTM identified 14 pathogen genotypes, including a majority of H. influenzae b, N. meningitidis B and S. pneumoniae 11A and 3A. In all 16 susceptible cultured bacteria, the in-silico antibiogram agreed with the in-vitro antibiogram in 10 cases, available within 48 h in routine bacteriology., Interpretation: In addition to pathogen detection, RTM applied to CSF samples offered supplementary information on bacterial profiling and genotyping. These data provide the proof-of-concept that RTM could be implemented in a POC laboratory for one-shot diagnostic and genomic surveillance of pathogens responsible for life-threatening meningitis., Funding: This work was supported by the French Government under the Investments in the Future programme managed by the National Agency for Research reference: Méditerranée Infection 10-IAHU-03., Competing Interests: Declaration of interests The authors declare no conflicts of interest. In particular, the authors did not receive any contribution from any of the suppliers mentioned in this report., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2022
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33. Antibiofilm Properties of Antiseptic Agents Used on Pseudomonas aeruginosa Isolated from Diabetic Foot Ulcers.
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Barrigah-Benissan K, Ory J, Dunyach-Remy C, Pouget C, Lavigne JP, and Sotto A
- Subjects
- Anti-Bacterial Agents, Biofilms, Humans, Pseudomonas aeruginosa, Sodium Hypochlorite pharmacology, Anti-Infective Agents, Local pharmacology, Diabetes Mellitus, Diabetic Foot drug therapy
- Abstract
In diabetic foot ulcers (DFUs), biofilm formation is a major challenge that promotes wound chronicity and delays healing. Antiseptics have been proposed to combat biofilms in the management of DFUs. However, there is limited evidence on the activity of these agents against biofilms, and there are questions as to which agents have the best efficiency. Here, we evaluated the antibiofilm activity of sodium hypochlorite, polyvinylpyrrolidoneIodine (PVPI), polyhexamethylenebiguanide (PHMB) and octenidine against Pseudomonas aeruginosa strains using static and dynamic systems in a chronic-wound-like medium (CWM) that mimics the chronic wound environment. Using Antibiofilmogram
® , a technology assessing the ability of antiseptics to reduce the initial phase of biofilm formation, we observed the significant activity of antiseptics against biofilm formation by P. aeruginosa (at 1:40 to 1:8 dilutions). Moreover, 1:100 to 1:3 dilutions of the different antiseptics reduced mature biofilms formed after 72 h by 10-log, although higher concentrations were needed in CWM (1:40 to 1:2). Finally, in the BioFlux200TM model, after biofilm debridement, sodium hypochlorite and PHMB were the most effective antiseptics. In conclusion, our study showed that among the four antiseptics tested, sodium hypochlorite demonstrated the best antibiofilm activity against P. aeruginosa biofilms and represents an alternative in the management of DFUs.- Published
- 2022
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34. Polymicrobial Biofilm Organization of Staphylococcus aureus and Pseudomonas aeruginosa in a Chronic Wound Environment.
- Author
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Pouget C, Dunyach-Remy C, Magnan C, Pantel A, Sotto A, and Lavigne JP
- Subjects
- Biofilms, Humans, Staphylococcus aureus, Wound Healing, Pseudomonas aeruginosa, Staphylococcal Infections
- Abstract
Biofilm on the skin surface of chronic wounds is an important step that involves difficulties in wound healing. The polymicrobial nature inside this pathogenic biofilm is key to understanding the chronicity of the lesion. Few in vitro models have been developed to study bacterial interactions inside this chronic wound. We evaluated the biofilm formation and the evolution of bacteria released from this biofilm on the two main bacteria isolated in this condition, Staphylococcus aureus and Pseudomonas aeruginosa, using a dynamic system (BioFlux™ 200) and a chronic wound-like medium (CWM) that mimics the chronic wound environment. We observed that all species constituted a faster biofilm in the CWM compared to a traditional culture medium (p < 0.01). The percentages of biofilm formation were significantly higher in the mixed biofilm compared to those determined for the bacterial species alone (p < 0.01). Biofilm organization was a non-random structure where S. aureus aggregates were located close to the wound surface, whereas P. aeruginosa was located deeper in the wound bed. Planktonic biofilm-detached bacteria showed decreased growth, overexpression of genes encoding biofilm formation, and an increase in the mature biofilm biomass formed. Our data confirmed the impact of the chronic wound environment on biofilm formation and on bacterial lifecycle inside the biofilm.
- Published
- 2022
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35. Taxonomical and functional changes in COVID-19 faecal microbiome could be related to SARS-CoV-2 faecal load.
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Grenga L, Pible O, Miotello G, Culotta K, Ruat S, Roncato MA, Gas F, Bellanger L, Claret PG, Dunyach-Remy C, Laureillard D, Sotto A, Lavigne JP, and Armengaud J
- Subjects
- Dysbiosis, Feces, Humans, RNA, Viral genetics, SARS-CoV-2 genetics, COVID-19, Microbiota genetics
- Abstract
Since the beginning of the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the gastrointestinal (GI) tract has emerged as an important organ influencing the propensity to and potentially the severity of the related COVID-19 disease. However, the contribution of the SARS-CoV-2 intestinal infection on COVID-19 pathogenesis remains to be clarified. In this exploratory study, we highlighted a possible link between alterations in the composition of the gut microbiota and the levels of SARS-CoV-2 RNA in the gastrointestinal tract, which could be more important than the presence of SARS-CoV-2 in the respiratory tract, COVID-19 severity and GI symptoms. As established by metaproteomics, altered molecular functions in the microbiota profiles of high SARS-CoV-2 RNA level faeces highlight mechanisms such as inflammation-induced enterocyte damage, increased intestinal permeability and activation of immune response that may contribute to vicious cycles. Uncovering the role of this gut microbiota dysbiosis could drive the investigation of alternative therapeutic strategies to favour the clearance of the virus and potentially mitigate the effect of the SARS-CoV-2 infection., (© 2022 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)
- Published
- 2022
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36. Bacterial Interactions in the Context of Chronic Wound Biofilm: A Review.
- Author
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Durand BARN, Pouget C, Magnan C, Molle V, Lavigne JP, and Dunyach-Remy C
- Abstract
Chronic wounds, defined by their resistance to care after four weeks, are a major concern, affecting millions of patients every year. They can be divided into three types of lesions: diabetic foot ulcers (DFU), pressure ulcers (PU), and venous/arterial ulcers. Once established, the classical treatment for chronic wounds includes tissue debridement at regular intervals to decrease biofilm mass constituted by microorganisms physiologically colonizing the wound. This particular niche hosts a dynamic bacterial population constituting the bed of interaction between the various microorganisms. The temporal reshuffle of biofilm relies on an organized architecture. Microbial community turnover is mainly associated with debridement (allowing transitioning from one major representant to another), but also with microbial competition and/or collaboration within wounds. This complex network of species and interactions has the potential, through diversity in antagonist and/or synergistic crosstalk, to accelerate, delay, or worsen wound healing. Understanding these interactions between microorganisms encountered in this clinical situation is essential to improve the management of chronic wounds.
- Published
- 2022
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37. Bacteriophage Therapy for Staphylococcus Aureus Infections: A Review of Animal Models, Treatments, and Clinical Trials.
- Author
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Plumet L, Ahmad-Mansour N, Dunyach-Remy C, Kissa K, Sotto A, Lavigne JP, Costechareyre D, and Molle V
- Subjects
- Animals, Anti-Bacterial Agents therapeutic use, Models, Animal, Staphylococcus aureus, Bacteriophages, Methicillin-Resistant Staphylococcus aureus, Phage Therapy, Staphylococcal Infections microbiology
- Abstract
Staphylococcus aureus ( S. aureus ) is a common and virulent human pathogen causing several serious illnesses including skin abscesses, wound infections, endocarditis, osteomyelitis, pneumonia, and toxic shock syndrome. Antibiotics were first introduced in the 1940s, leading to the belief that bacterial illnesses would be eradicated. However, microorganisms, including S. aureus , began to develop antibiotic resistance from the increased use and abuse of antibiotics. Antibiotic resistance is now one of the most serious threats to global public health. Bacteria like methicillin-resistant Staphylococcus aureus (MRSA) remain a major problem despite several efforts to find new antibiotics. New treatment approaches are required, with bacteriophage treatment, a non-antibiotic strategy to treat bacterial infections, showing particular promise. The ability of S. aureus to resist a wide range of antibiotics makes it an ideal candidate for phage therapy studies. Bacteriophages have a relatively restricted range of action, enabling them to target pathogenic bacteria. Their usage, usually in the form of a cocktail of bacteriophages, allows for more focused treatment while also overcoming the emergence of resistance. However, many obstacles remain, particularly in terms of their effects in vivo , necessitating the development of animal models to assess the bacteriophage efficiency. Here, we provide a review of the animal models, the various clinical case treatments, and clinical trials for S. aureus phage therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Plumet, Ahmad-Mansour, Dunyach-Remy, Kissa, Sotto, Lavigne, Costechareyre and Molle.)
- Published
- 2022
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38. Comparative genomics analysis of two Helcococcus kunzii strains co-isolated with Staphylococcus aureus from diabetic foot ulcers.
- Author
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Durand BARN, Yahiaoui Martinez A, Baud D, François P, Lavigne JP, and Dunyach-Remy C
- Subjects
- Humans, Staphylococcus aureus genetics, Genomics, Diabetic Foot microbiology, Staphylococcal Infections microbiology, Diabetes Mellitus
- Abstract
Helcococcus kunzii is a commensal Gram-positive bacterial species recovered from the human skin microbiota and considered as an opportunistic pathogen. Although little is known about its clinical significance, its increased abundance has been reported in infected wounds, particularly in foot ulcers in persons with diabetes. This species is usually detected in mixed cultures from human specimens and frequently isolated with Staphylococcus aureus. Modulation of staphylococci virulence by H. kunzii has been shown in an infection model of Caenorhabditis elegans. The aim of this study was to compare the genomes of two H. kunzii strains isolated from foot ulcers -isolate H13 and H10 showing high or low impact on S. aureus virulence, respectively- and the H. kunzii ATCC51366 strain. Whole genome analyses revealed some differences between the two strains: length (2.06 Mb (H13) and 2.05 Mb (H10) bp), GC content (29.3% (H13) and 29.5% (H10)) and gene content (1,884 (H13) and 1,786 (H10) predicted genes). The core-proteome phylogenies within the genus characterised H. kunzii H13 and H10 as genetically similar to their ancestor. The main differences between the strains were mainly in sugar-associated transporters and various hypothetical proteins. Five targets were identified as potentially involved in S. aureus virulence modulation in both genomes: the two-component iron export system and three autoinducer-like proteins. Moreover, H13 strain harbours a prophage inserted in 1,261,110-1,295,549 (attL-attR), which is absent in H10 strain. The prophage PhiCD38_2 was previously reported for its ability to modulate secretion profile, reinforcing the autoinducer-like hypothesis. In the future, transcriptomics or metaproteomics approaches could be performed to better characterize the H13 strain and possibly identify the underlying mechanism for S. aureus virulence modulation., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)
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- 2022
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39. A Relevant Wound-Like in vitro Media to Study Bacterial Cooperation and Biofilm in Chronic Wounds.
- Author
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Pouget C, Dunyach-Remy C, Bernardi T, Provot C, Tasse J, Sotto A, and Lavigne JP
- Abstract
Biofilm on the skin surface of chronic wounds is an important factor in the pathology, inhibiting wound healing. The polymicrobial nature of these infected wounds and bacterial interactions inside this pathogenic biofilm are the keys for understanding chronic infection. The aim of our work was to develop an innovative in vitro medium that closely mimics the chronic wound emphasizing the microbiological, cellular, and inflammatory environment of chronic wounds but also focusing on the pH found at the wound level. This new medium, called chronic wound medium (CWM), will thus facilitate the study of pathogenic biofilm organization. Clinical Staphylococcus aureus and Pseudomonas aeruginosa strains coisolated from diabetic foot infection were collected and cultivated in this new medium for 24 h in monoculture and coculture. Bacterial growth (growth curves), presence of small colony variant (SCV), biofilm formation (BioFilm Ring Test
® assay, biofilm biomass quantification), and virulence (survival curve in a Caenorhabditis elegans model) were evaluated. After 24 h in the in vitro conditions, we observed that P. aeruginosa growth was not affected, compared with a control bacterial medium, whereas for S. aureus , the stationary phase was reduced by two logs. Interestingly, S. aureus growth increased when cocultured with P. aeruginosa in CWM. In coculture with P. aeruginosa , SCV forms of S. aureus were detected. Biofilm studies showed that bacteria, alone and in combination, formed biofilm faster (as soon as 3 h) than the bacteria exposed in a control medium (as soon as 5 h). The virulence of all strains decreased in the nematode model when cultivated in our new in vitro medium. Taken together, our data confirmed the impact of the chronic wound environment on biofilm formation and bacteria virulence. They indicated that P. aeruginosa and S. aureus cooperated in coinfected wounds. Therefore, this in vitro model provides a new tool for bacterial cooperation investigation and polymicrobial biofilm formation., Competing Interests: The authors were co-inventors of the CWM (European patent application EP21305337, filed on 18 March 2021). CPo was the recipient of a grant from Biofilm Pharma (Bourse CIFRE). CPo, TB, CPr, and JT were employed by Biofilm Pharma SAS., (Copyright © 2022 Pouget, Dunyach-Remy, Bernardi, Provot, Tasse, Sotto and Lavigne.)- Published
- 2022
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40. Deciphering Black Extrinsic Tooth Stain Composition in Children Using Metaproteomics.
- Author
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Hirtz C, Mannaa AM, Moulis E, Pible O, O'Flynn R, Armengaud J, Jouffret V, Lemaistre C, Dominici G, Martinez AY, Dunyach-Remy C, Tiers L, Lavigne JP, Tramini P, Goldsmith MC, Lehmann S, Deville de Périère D, and Vialaret J
- Abstract
The present study focuses on the use of a metaproteomic approach to analyze Black Extrinsic Tooth Stains, a specific type of pigmented extrinsic substance. Metaproteomics is a powerful emerging technology that successfully enabled human protein and bacterial identification of this specific dental biofilm using high-resolution tandem mass spectrometry. A total of 1600 bacterial proteins were identified in black stain (BS) samples and 2058 proteins in dental plaque (DP) samples, whereas 607 and 582 human proteins were identified in BS and DP samples, respectively. A large diversity of bacteria genera (142) in BS and DP was identified, showing a high prevalence of Rothia, Kingella, Neisseria, and Pseudopropionibacterium in black stain samples. In this work, the high diversity of the dental microbiota and its proteome is highlighted, including significant differences between black stain and dental plaque samples., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)
- Published
- 2022
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41. Analysis of Microbial Communities: An Emerging Tool in Forensic Sciences.
- Author
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Gouello A, Dunyach-Remy C, Siatka C, and Lavigne JP
- Abstract
The objective of forensic sciences is to find clues in a crime scene in order to reconstruct the scenario. Classical samples include DNA or fingerprints, but both have inherent limitations and can be uninformative. Another type of sample has emerged recently in the form of the microbiome. Supported by the Human Microbiome Project, the characteristics of the microbial communities provide real potential in forensics. They are highly specific and can be used to differentiate and classify the originating body site of a human biological trace. Skin microbiota is also highly specific and different between individuals, leading to its possibility as an identification tool. By extension, the possibilities of the microbial communities to be deposited on everyday objects has also been explored. Other uses include the determination of the post-mortem interval or the analysis of soil communities. One challenge is that the microbiome changes over time and can be influenced by many environmental and lifestyle factors. This review offers an overview of the main methods and applications to demonstrate the benefit of the microbiome to provide forensically relevant information.
- Published
- 2021
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42. Editorial: Microbial Biofilms in Chronic and Recurrent Infections.
- Author
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Ascenzioni F, Cloeckaert A, Di Domenico EG, Dunyach-Remy C, and Guembe M
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2021
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43. The Persistence of Staphylococcus aureus in Pressure Ulcers: A Colonising Role.
- Author
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Fayolle M, Morsli M, Gelis A, Chateauraynaud M, Yahiaoui-Martinez A, Sotto A, Lavigne JP, and Dunyach-Remy C
- Subjects
- Adult, Aged, Biofilms growth & development, Female, Genome, Bacterial genetics, Humans, Male, Middle Aged, Virulence genetics, Pressure Ulcer microbiology, Staphylococcal Infections microbiology, Staphylococcus aureus genetics
- Abstract
Decubitus pressure ulcers (PU) are a major complication of immobilised patients. Staphylococcus aureus is one of the most frequently detected microorganisms in PU samples; however, its persistence and role in the evolution of these wounds is unknown. In this study, we analysed S. aureus strains isolated from PU biopsies at inclusion and day 28. Eleven S. aureus (21.1%) were detected in 52 patients at inclusion. Only six PUs (11.5%) continued to harbour this bacterium at day 28. Using a whole genome sequencing approach (Miseq
® , Illumina), we confirmed that these six S. aureus samples isolated at D28 were the same strain as that isolated at inclusion, with less than 83 bp difference. Phenotypical studies evaluating the growth profiles (Infinite M Mano, Tecan® ) and biofilm formation (Biofilm Ring Test® ) did not detect any significant difference in the fitness of the pairs of S. aureus . However, using the Caenorhabditis elegans killing assay, a clear decrease of virulence was observed between strains isolated at D28 compared with those isolated at inclusion, regardless of the clinical evolution of the PU. Moreover, all strains at inclusion were less virulent than a control S. aureus strain, i.e., NSA739. An analysis of polymicrobial communities of PU (by metabarcoding approach), in which S. aureus persisted, demonstrated no impact of Staphylococcus genus on PU evolution. Our study suggested that S. aureus presented a colonising profile on PU with no influence on wound evolution.- Published
- 2021
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44. Synthesis, Structure Elucidation, Antibacterial Activities, and Synergistic Effects of Novel Juglone and Naphthazarin Derivatives Against Clinical Methicillin-Resistant Staphylococcus aureus Strains.
- Author
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Duvauchelle V, Majdi C, Bénimélis D, Dunyach-Remy C, Meffre P, and Benfodda Z
- Abstract
Infections caused by drug-resistant bacteria are a serious threat to human and global public health. Moreover, in recent years, very few antibiotics have been discovered and developed by pharmaceutical companies. Therefore, there is an urgent need to discover and develop new antibacterial agents to combat multidrug-resistant bacteria. In this study, two novel series of juglone/naphthazarin derivatives (43 compounds) were synthesized and evaluated for their antibacterial properties against various clinical and reference Gram-positive MSSA, clinical Gram-positive MRSA, and clinical and reference Gram-negative bacteria E. coli and P. aeruginosa . These strains are of clinical importance because they belong to ESKAPE pathogens. Compounds 3al , 5ag , and 3bg showed promising activity against clinical and reference MSSA (MIC: 1-8 µg/ml) and good efficacy against clinical MRSA (MIC: 2-8 µg/ml) strains. 5am and 3bm demonstrated better activity on both MSSA (MIC: 0.5 µg/ml) and MRSA (MIC: 2 µg/ml) strains. Their MICs were similar to those of cloxacillin against clinical MRSA strains. The synergistic effects of active compounds 3al , 5ag , 5am , 3bg , and 3bm were evaluated with reference antibiotics, and it was found that the antibiotic combination with 3bm efficiently enhanced the antimicrobial activity. Compound 3bm was found to restore the sensitivity of clinical MRSA to cloxacillin and enhanced the antibacterial activity of vancomycin when they were added together. In the presence of 3bm , the MIC values of vancomycin and cloxacillin were lowered up to 1/16th of the original MIC with an FIC index of 0.313. Moreover, compounds 3al , 5ag , 5am , 3bg , and 3bm did not present hemolytic activity on sheep red blood cells. In silico prediction of ADME profile parameter results for 3bm is promising and encouraging for further development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Duvauchelle, Majdi, Bénimélis, Dunyach-Rémy, Meffre and Benfodda.)
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- 2021
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45. First Report of CC5-MRSA-IV-SCC fus "Maltese Clone" in Bat Guano.
- Author
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Mairi A, Touati A, Pantel A, Yahiaoui Martinez A, Ahmim M, Sotto A, Dunyach-Remy C, and Lavigne JP
- Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is a widespread pathogen that could cause different illnesses in both human and animals. Presence of MRSA in animals raises concerns of their capacity to act as reservoirs, particularly in wild animals. This study aimed to characterize the resistance and virulence patterns of S. aureus strains isolated from bat guano in Algeria. From March to May 2016, 98 bat guano samples from Aokas's cave (Bejaia, Algeria) were collected. Swabs were taken for microbiological studies. Isolates were identified by Vitek
® MS system, and antibiotic susceptibility was determined by disk diffusion method. The clonal origin, virulence and antibiotic resistance profiles of S. aureus isolates were characterized by whole genome sequencing. Eleven S. aureus strains were obtained from the 98 guano samples. Seven isolates were sensitive to all antibiotics tested and four (36.3%) were resistant to penicillin G, cefoxitin and fusidic acid. The four MRSA isolates were assigned to the sequence type ST149 and related to spa type t 010. These isolates harbored a SCC mec IV element and the fusidic acid resistance element Q6GD50 ( fusC ). They carried different virulence genes including several enterotoxins ( sea , egc enterotoxin locus, sec , sel ), and the toxic shock syndrome toxin ( tst ). Our results highlight that bat guano may constitute an important reservoir of MRSA strains.- Published
- 2021
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46. Biofilm Formation in Methicillin-Resistant Staphylococcus aureus Isolated in Cystic Fibrosis Patients Is Strain-Dependent and Differentially Influenced by Antibiotics.
- Author
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Boudet A, Sorlin P, Pouget C, Chiron R, Lavigne JP, Dunyach-Remy C, and Marchandin H
- Abstract
Cystic fibrosis (CF) is a genetic disease with lung abnormalities making patients particularly predisposed to pulmonary infections. Staphylococcus aureus is the most frequently identified pathogen, and multidrug-resistant strains (MRSA, methicillin-resistant S. aureus ) have been associated with more severe lung dysfunction leading to eradication recommendations. Diverse bacterial traits and adaptive skills, including biofilm formation, may, however, make antimicrobial therapy challenging. In this context, we compared the ability of a collection of genotyped MRSA isolates from CF patients to form biofilm with and without antibiotics (ceftaroline, ceftobiprole, linezolid, trimethoprim, and rifampicin). Our study used standardized approaches not previously applied to CF MRSA, the BioFilm Ring test® (BRT®), the Antibiofilmogram®, and the BioFlux™ 200 system which were adapted for use with the artificial sputum medium (ASM) mimicking conditions more relevant to the CF lung. We included 63 strains of 10 multilocus sequence types (STs) isolated from 35 CF patients, 16 of whom had chronic colonization. The BRT® showed that 27% of the strains isolated in 37% of the patients were strong biofilm producers. The Antibiofilmogram® performed on these strains showed that broad-spectrum cephalosporins had the lowest minimum biofilm inhibitory concentrations (bMIC) on a majority of strains. A focus on four chronically colonized patients with inclusion of successively isolated strains showed that ceftaroline, ceftobiprole, and/or linezolid bMICs may remain below the resistance thresholds over time. Studying the dynamics of biofilm formation by strains isolated 3years apart in one of these patients using BioFlux™ 200 showed that inhibition of biofilm formation was observed for up to 36h of exposure to bMIC and ceftaroline and ceftobiprole had a significantly greater effect than linezolid. This study has brought new insights into the behavior of CF MRSA which has been little studied for its ability to form biofilm. Biofilm formation is a common characteristic of prevalent MRSA clones in CF. Early biofilm formation was strain-dependent, even within a sample, and not only observed during chronic colonization. Ceftaroline and ceftobiprole showed a remarkable activity with a long-lasting inhibitory effect on biofilm formation and a conserved activity on certain strains adapted to the CF lung environment after years of colonization., Competing Interests: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2021 Boudet, Sorlin, Pouget, Chiron, Lavigne, Dunyach-Remy and Marchandin.)
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- 2021
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47. Alternative Approaches for the Management of Diabetic Foot Ulcers.
- Author
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Pouget C, Dunyach-Remy C, Pantel A, Boutet-Dubois A, Schuldiner S, Sotto A, Lavigne JP, and Loubet P
- Abstract
Diabetic foot ulcers (DFU) represent a growing public health problem. The emergence of multidrug-resistant (MDR) bacteria is a complication due to the difficulties in distinguishing between infection and colonization in DFU. Another problem lies in biofilm formation on the skin surface of DFU. Biofilm is an important pathophysiology step in DFU and may contribute to healing delays. Both MDR bacteria and biofilm producing microorganism create hostile conditions to antibiotic action that lead to chronicity of the wound, followed by infection and, in the worst scenario, lower limb amputation. In this context, alternative approaches to antibiotics for the management of DFU would be very welcome. In this review, we discuss current knowledge on biofilm in DFU and we focus on some new alternative solutions for the management of these wounds, such as antibiofilm approaches that could prevent the establishment of microbial biofilms and wound chronicity. These innovative therapeutic strategies could replace or complement the classical strategy for the management of DFU to improve the healing process., Competing Interests: CP is the recipient of a grant from Biofilm Control (Bourse CIFRE). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pouget, Dunyach-Remy, Pantel, Boutet-Dubois, Schuldiner, Sotto, Lavigne and Loubet.)
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- 2021
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48. New Adapted In Vitro Technology to Evaluate Biofilm Formation and Antibiotic Activity Using Live Imaging under Flow Conditions.
- Author
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Pouget C, Dunyach-Remy C, Pantel A, Schuldiner S, Sotto A, and Lavigne JP
- Abstract
The polymicrobial nature of biofilms and bacterial interactions inside chronic wounds are keys for the understanding of bacterial cooperation. The aim of this present study was to develop a technique to study and visualize biofilm in live imaging under flow conditions (Bioflux™ 200, Fluxion Biosciences). The Bioflux
TM system was adapted using an in vitro chronic wound-like medium (CWM) that mimics the environment encountered in ulcers. Two reference strains of Staphylococcus aureus (Newman) and Pseudomonas aeruginosa (PAO1) were injected in the BiofluxTM during 24 h to 72 h in mono and coculture (ratio 1:1, bacteria added simultaneously) in the CWM vs. a control medium (BHI). The quantification of biofilm formation at each time was evaluated by inverted microscopy. After 72 h, different antibiotics (ceftazidime, imipenem, linezolid, oxacillin and vancomycin) at 1x MIC, 10x MIC and 100x MIC were administrated to the system after an automatic increase of the flow that mimicked a debridement of the wound surface. Biofilm studies highlighted that the two species, alone or associated, constituted a faster and thicker biofilm in the CWM compared to the BHI medium. The effect of antibiotics on mature or "debrided" biofilm indicated that some of the most clinically used antibiotic such as vancomycin or imipenem were not able to disrupt and reduce the biofilm biomass. The use of a life cell imaging with an in vitro CWM represents a promising tool to study bacterial biofilm and investigate microbial cooperation in a chronic wound context.- Published
- 2021
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49. Staphylococcus aureus Toxins: An Update on Their Pathogenic Properties and Potential Treatments.
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Ahmad-Mansour N, Loubet P, Pouget C, Dunyach-Remy C, Sotto A, Lavigne JP, and Molle V
- Subjects
- Staphylococcus aureus metabolism, Staphylococcus aureus pathogenicity, Virulence Factors antagonists & inhibitors, Virulence Factors metabolism, Anti-Bacterial Agents pharmacology, Staphylococcus aureus drug effects, Toxins, Biological metabolism, Virulence drug effects
- Abstract
Staphylococcus aureus is a clinically important pathogen that causes a wide range of human infections, from minor skin infections to severe tissue infection and sepsis. S. aureus has a high level of antibiotic resistance and is a common cause of infections in hospitals and the community. The rising prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA), combined with the important severity of S. aureus infections in general, has resulted in the frequent use of anti-staphylococcal antibiotics, leading to increasing resistance rates. Antibiotic-resistant S. aureus continues to be a major health concern, necessitating the development of novel therapeutic strategies. S. aureus uses a wide range of virulence factors, such as toxins, to develop an infection in the host. Recently, anti-virulence treatments that directly or indirectly neutralize S. aureus toxins have showed promise. In this review, we provide an update on toxin pathogenic characteristics, as well as anti-toxin therapeutical strategies.
- Published
- 2021
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50. Pressure ulcers microbiota dynamics and wound evolution.
- Author
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Dunyach-Remy C, Salipante F, Lavigne JP, Brunaud M, Demattei C, Yahiaoui-Martinez A, Bastide S, Palayer C, Sotto A, and Gélis A
- Subjects
- Aged, Bacteria genetics, Female, Humans, Male, Middle Aged, Bacteria isolation & purification, Microbiota physiology, Pressure Ulcer microbiology, RNA, Ribosomal, 16S genetics, Wound Healing
- Abstract
Bacterial species and their role in delaying the healing of pressure ulcers (PU) in spinal cord injury (SCI) patients have not been well described. This pilot study aimed to characterise the evolution of the cutaneous microbiota of PU in SCI cohort. Twenty-four patients with SCI from a French neurological rehabilitation centre were prospectively included. PU tissue biopsies were performed at baseline (D0) and 28 days (D28) and analysed using 16S rRNA gene-based sequencing analysis of the V3-V4 region. At D0, if the overall relative abundance of genus highlighted a large proportion of Staphylococcus, Anaerococcus and Finegoldia had a significantly higher relative abundance in wounds that stagnated or worsened in comparison with those improved at D28 (3.74% vs 0.05%; p = 0.015 and 11.02% versus 0.16%; p = 0.023, respectively). At D28, Proteus and Morganella genera were only present in stagnated or worsened wounds with respectively 0.02% (p = 0.003) and 0.01% (p = 0.02). Moreover, Proteus, Morganella, Anaerococcus and Peptoniphilus were associated within the same cluster, co-isolated from biopsies that had a poor evolution. This pathogroup could be a marker of wound degradation and Proteus could represent a promising target in PU management., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
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